Biocellulose patch technique for fetoscopic repair of open spina bifida in twin pregnancy.

OBJECTIVES: Twin pregnancy is currently an exclusion criterion for prenatal repair of open spina bifida (OSB). The main objective of this study was to report on our experience of treating twin pregnancies with OSB using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique. We also discuss reconsideration of the current exclusion criteria for fetal OSB repair. METHODS: Eight fetuses with OSB from seven twin pregnancies underwent successful prenatal repair. Six pregnancies were dichorionic diamniotic with only one twin affected, and one was monochorionic diamniotic with both twins affected. Percutaneous fetoscopy was performed under CO2 insufflation of the sac of the affected twin. Neurosurgical repair was performed using a biocellulose patch to protect the placode, with the skin sutured to hold the patch in place, with or without a myofascial flap. Neurodevelopment was assessed using the pediatric evaluation of disability inventory scale in babies older than 6 months of adjusted age, whereas the Alberta scale was used for babies younger than 6 months of adjusted age. RESULTS: All 14 fetuses were liveborn and none required additional repair. Gestational age at surgery ranged from 27.3 to 31.1 weeks, and gestational age at birth ranged from 31.6 to 36.0 weeks. Four out of eight affected twins developed sepsis, but had a good recovery. No sequela of prematurity was found in any of the unaffected twins. Short-term neurodevelopment was normal in all evaluated unaffected twins (5/5) and in all but one affected twins (7/8). In the affected group, only one baby required ventriculoperitoneal shunt placement. CONCLUSIONS: Prematurity is frequent after fetal surgery, and the risk is increased in twin pregnancy. Nevertheless, prenatal surgery using the SAFER technique is feasible, with low risk to both twins and their mother when performed by a highly experienced team. Long-term cognitive assessment of the unaffected twin is needed. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Percutaneous fetoscopic closure of large open spina bifida using a bilaminar skin substitute.

OBJECTIVE: We have described previously our percutaneous fetoscopic technique for the treatment of open spina bifida (OSB). However, approximately 20-30% of OSB defects are too large to allow primary skin closure. Here we describe a modification of our standard technique using a bilaminar skin substitute to allow closure of large spinal defects. The aim of this study was to report our clinical experience with the use of a bilaminar skin substitute and a percutaneous fetoscopic technique for the prenatal closure of large OSB defects. METHODS: Surgery was performed between 24.0 and 28.9 gestational weeks with the woman under general anesthesia, using an entirely percutaneous fetoscopic approach with partial carbon dioxide insufflation of the uterine cavity, as described previously. If there was enough skin to be sutured in the midline, only a biocellulose patch was placed over the placode (single-patch group). In cases in which skin approximation was not possible, a bilaminar skin substitute (two layers: one silicone and one dermal matrix) was placed over the biocellulose patch and sutured to the skin edges (two-patch group). The surgical site was assessed at birth, and long-term follow-up was carried out. RESULTS: Percutaneous fetoscopic OSB repair was attempted in 47 consecutive fetuses, but surgery could not be completed in two. Preterm prelabor rupture of membranes (PPROM) occurred in 36 of the 45 (80%) cases which formed the study group, and the mean gestational age at delivery was 32.8 ± 2.5 weeks. A bilaminar skin substitute was required in 13/45 (29%) cases; in the remaining 32 cases, direct skin-to-skin suture was feasible. There were 12 cases of myeloschisis, of which 10 were in the two-patch group. In all cases, the skin substitute was located at the surgical site at birth. In five of the 13 (38.5%) cases in the two-patch group, additional postnatal repair was needed. In the remaining cases, the silicone layer detached spontaneously from the dermal matrix (on average, 25 days after birth), and the lesion healed by secondary intention. The mean operating time was 193 (range, 83-450) min; it was significantly longer in cases requiring the bilaminar skin substitute (additional 42 min on average), although the two-patch group had similar PPROM rate and gestational age at delivery compared with the single-patch group. Complete reversal of hindbrain herniation occurred in 68% of the 28 single-patch cases and 33% of the 12 two-patch cases with this information available (P < 0.05). In four cases there was no reversal; half of these occurred in myeloschisis cases. CONCLUSIONS: Large OSB defects may be treated successfully in utero using a bilaminar skin substitute over a biocellulose patch through an entirely percutaneous approach. Although the operating time is longer, surgical outcome is similar to that in cases closed primarily. Cases with myeloschisis seem to have a worse prognosis than do those with myelomeningocele. PPROM and preterm birth continue to be a challenge. Further experience is needed to assess the risks and benefits of this technique for the management of large OSB defects. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Invasive Fungal Disease in Renal Transplant Recipients at a Brazilian Center: Local Epidemiology Matters.

INTRODUCTION: Invasive fungal disease (IFD) is an important complication after solid organ transplantation (SOT). A marked geographic variation in the epidemiology of IFD after kidney transplantation (KT) has been suggested by the results of previous studies. Nevertheless, data from Latin American centers are scarce. OBJECTIVE: This study sought to describe the epidemiology of IFD at a Brazilian KT center. METHODS: This study was a retrospective single-center cohort study that included patients who underwent KT between 1998 and 2009 and were followed up until July 2015. Cases of simultaneous kidney-pancreas transplantation were excluded. The primary study outcome was the occurrence of proven or probable IFD. RESULTS: Among 908 KT recipients, 44 cases of IFD occurred in 42 patients (4.6%). Cryptococcus spp. infection, diagnosed in 16 cases (36.3%), was the leading cause of IFD, followed by histoplasmosis in 10 cases (22.7%) and invasive candidiasis in 10 (22.7%). Sporotrichosis, mucormycosis, invasive aspergillosis, pulmonary Cladophialophora sp. infection, trichosporonosis and Saccharomyces cerevisiae fungemia occurred in 1 recipient each (2.3%). Two additional (4.5%) cases of unspecified mold infections were identified by histopathological analysis. Most cases of IFD (67%) occurred later than 6 months after transplantation. Previous use of antilymphocyte antibodies (P = .008) and corticosteroid pulse therapy (P < .001) were more frequent among cases of IFD occurring within the first 6 months after transplantation. CONCLUSIONS: The epidemiology of IFD in this Brazilian cohort was characterized by a large predominance of late infections and a high proportion of cases of cryptococcosis and histoplasmosis. These results highlight the considerable geographic variability of IFD epidemiology after KT.

Outcome of bacteremia caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae after solid organ transplantation.

INTRODUCTION: Although infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) has been recognized as an important cause of morbidity after solid organ transplantation, there are limited data on the outcome of this complication among transplant recipients. The objective of this study was to describe the outcome and factors associated with mortality among recipients of abdominal solid organ transplants with bloodstream infection caused by ESBL-E. PATIENTS AND METHODS: This study was a retrospective analysis of a case series of patients who had bacteremia caused by ESBL-E after undergoing renal or liver transplantation between January 2000 and September 2008 at a university-affiliated hospital in Rio de Janeiro, Brazil. The primary end point of the study was death within 30 days of the diagnosis of bacteremia. RESULTS: During the study period, 997 subjects underwent kidney (759 patients) or liver (238 patients) transplantation. Fifty-four episodes of bacteremia caused by ESBL-E were diagnosed in 39 patients (4%). Mortality after the first episode of ESBL-E bacteremia was 26% (10 deaths). In multiple logistic regression analysis, the Pitt bacteremia score (P = .005) and being on mechanical ventilation at the time of infection diagnosis (P = .02) were the only variables associated with mortality. Thirteen episodes of recurrent bacteremia occurred in 8 (28%) of the 29 patients who survived the first episode. Two (25%) of these 8 patients died during the course of a recurrent episode. CONCLUSIONS: Bacteremia caused by ESBL-E was associated with high mortality and high risk of recurrence. Factors associated with clinical severity at the time of infection diagnosis were the main predictors of mortality.

Results of implementation of preventive recommendations for tuberculosis after renal transplantation in an endemic area.

This retrospective cohort study assessed the results of the implementation of preventive recommendations for tuberculosis (TB) among renal transplant recipients in an endemic area (Rio de Janeiro, Brazil). Subjects were defined as at high risk for TB if they had latent tuberculosis infection (LTBI), reported recent close contact with individuals with TB or received a graft from a donor with LTBI. A 6-month course of isoniazid preventive therapy (IPT) was targeted to high-risk subjects. The study end point was TB confirmed by culture. Altogether, 535 patients were included. Median follow-up was 59 months. The overall cumulative incidence of TB was 2.1% while among the 274 patients in whom the preventive protocol was fully implemented, the incidence was only 0.7%. The incidence of TB among 75 high-risk recipients not treated with isoniazid (7%) was significantly higher than that observed in 209 untreated low-risk patients (1%, p = 0.006) and in 65 high-risk subjects that received IPT (no case, p = 0.03). In conclusion, the implementation of preventive recommendations for TB in an endemic area allowed the appropriate discrimination between high- and low-risk renal transplant recipients and was associated with long-term reduction in the incidence of this complication among high-risk subjects.

Effects of immunosuppressant FK-506 on tooth movement.

OBJECTIVE: To test the hypothesis that immunosuppressant tacrolimus treatment can interfere with bone turnover and rate of tooth movement. MATERIAL AND METHODS: One-hundred twenty Wistar male rats were divided into four groups: Group 1 (rats subjected to orthodontic movement plus treatment with saline solution vehicle), Group 2 (rats subjected to orthodontic movement plus treatment with FK506), Group 3 (rats treated with FK506 only), and Group 4 (rats treated with saline solution vehicle). The maxillary incisors were laterally moved with a reciprocal load of 35 cN. The dosage of FK506 was 2 mg/kg/day. Howship's lacunae, osteoclasts, and macrophages were counted. RESULTS: Tooth movement was found to be greater in Group 1 than in Group 2 for all time periods (on days 3, 7, and 14), although a significant difference was observed only on days 7 and 14 (p < 0.05). The number of osteoclasts was smaller in Group 1 than in Group 2, whereas the number of Howship's lacunae was greater. CONCLUSION: FK506 has the capacity of promoting osteoclasts inhibition with probable osteoclastic apoptosis of alveolar bone following tooth movement.

Comparison of the safety and efficacy of cyclosporine minimization versus cyclosporine elimination in de novo renal allograft patients receiving sirolimus.

The safety and efficacy of concentration-controlled use of sirolimus (SRL) and cyclosporine (CsA) followed by CsA minimization (CsAm) or elimination (CsAe) beginning at week 13 was compared in a phase 4, open-label, randomized (1:1) trial of renal transplant recipients enrolled between March 2004 and November 2005. The primary endpoint was renal function, measured at 12 months using the Nankivell formula, in patients remaining on therapy. Though a total enrollment of 140 patients in each group was planned to provide an 80% power to detect a difference in means, only 207 subjects were enrolled in this study. Demographic characteristics were similar between groups, with 98.1% recipients of first grafts, 69.1% from living donors, and 7.2% diabetics. At 12 months, there were no differences in renal function (61.08 vs 65.24 mL/min, P = .132); incidence of biopsy-confirmed acute rejection (14.3% vs 22.5%, P = .152); and patient (89.5% vs 92.2%, P = .632), graft (87.6% vs 88.2%, P = .999), and death-censored graft (98.1% vs 94.1%, P = .166) survivals between CsAm and CsAe groups, respectively. There were no differences in the overall rate of study-drug discontinuation (32.4% vs 36.3%, P = .562) but more patients discontinued because of lack of efficacy/graft loss in the CsAe group (4.8% vs 14.7%, P = .018). This study was underpowered to demonstrate the superiority of one regimen over the other. In summary, SRL immunotherapy combined with CsA minimization or elimination showed comparative safety and efficacy. Both regimens offer potential treatment options for de novo renal allograft recipients.

Urinary tract infections in renal transplant recipients: virulence traits of uropathogenic Escherichia coli.

BACKGROUND: Urinary tract infection (UTI) is the most common infectious complication after renal transplantation. Most infections are caused by uropathogenic Escherichia coli (UPEC). There are limited data on the prevalence of virulence traits among UPEC isolated from renal transplant recipients. This study compared the phenotypic and genotypic profiles of UPEC strains isolated from recipients with those from control patients. METHODS: E coli isolates that caused UTI in recipients versus nonimmunosuppressed control patients were characterized according to phylogenetic group and the presence of urovirulence genes pap1/pap2; sfa1/sfa2; afa1/afa2; aer1/aer2; and cnf1/cnf2. RESULTS: Thirty-six UPEC isolates from recipients and another 27 from control individuals were included in the study. The proportion of episodes of pyelonephritis in recipients (50%) versus control subjects (41%) was similar (P = .46). However, secondary bacteremia was observed only among recipients (n = 8; P < .001). There was no significant difference in the distribution of phylogenetic groups or the prevalence of analyzed virulence traits between UPEC isolated from the 2 groups. Nevertheless, strains associated with secondary bacteremia in recipients showed a higher prevalence of mannose-resistant hemagglutination (P = .013). CONCLUSION: The phenotypic and genotypic characteristics of UPEC isolated from recipients were similar to those from control patients at a tertiary care center. Secondary bacteremia in recipients was associated with a higher prevalence of mannose-resistant hemagglutination.

Corticosteroid reduction with tacrolimus (CORRETA) TRIAL: a prospective Brazilian multicenter, randomized trial of early corticosteroid reduction versus regular corticosteroid dosage maintenance on a tacrolimus (Prograf) and mycophenolate mofetil (Cellcept) immunosuppression regimen in kidney transplant recipients: interim analysis.

Corticosteroids are a cornerstone of immunosuppressive therapy in renal transplantation despite their side effects and morbidity. Newer immunosuppressive agents may be more effective to allow corticosteroid sparing. An interim analysis of 60 completed out of 100 planned primary kidney transplant recipients is presented. All patients on tacrolimus (Prograf) and MMF (Cellcept) were randomized into two groups following a 1:1 distribution for early steroid reduction at posttransplant day 7 (G1; n = 31) versus to long-term maintenance steroids (G2; n = 29). Primary efficacy endpoints were composite endpoint of death, graft loss, or severe acute rejection at 6 and 12 months follow-up. Safety evaluation included severity and frequency of diabetes mellitus, hypertension, hyperlipidemia, leukopenia, infection, malignancy, and severe adverse events. Mean age was 39.1 years, with 45.0% males and 66.7% Caucasians. African-Americans were 25.8% in G1 and 27.6% in G2. One death occurred in each group, as well as one case of severe (Banff III) rejection in G1 (P = 1.00). The incidence of rejection episodes between groups was not significant, namely, 41.9% in G1 and 20.7% in G2 (P = .077). There were no differences between groups concerning mean, systolic and diastolic blood pressure, HbA1c, or creatinine at 12 months. This interim analysis showed no evidence of an increased risk of poorer performance among the early steroid reduction or safety differences in kidney transplant recipients versus a regular dosage steroid group of patients. Further analysis of the complete study data is underway.

Incidence of delayed graft function in cadaveric kidney transplants in Brazil: a multicenter analysis.

To evaluate the frequency of delayed graft function (DGF) in kidney transplant centers in Brazil, we sent a questionnaire requesting information on the number of cadaveric donor kidney transplants performed during the years 2000, 2001, and 2002, the number of early nonfunctioning grafts, and the number of patients on dialysis during the first posttransplant week with subsequent recovery. Among all centers performing more than 50 kidney transplants during the last year of evaluation, 6, performing 612 cadaveric kidney transplants during the study period, replied to the questionnaire. Sixty procedures (9.7%) resulted in nonfunctioning grafts, while 312 (55.6%) patients required dialysis during the first Ptx week: 216 (53.9%) in 2000, 189 (62.3%) in 2001, and 216 (51.6%) in 2002. The frequency of DGF during the study period was higher than that noted by several previous foreign studies. To better evaluate the possible causes of this finding, a more extensive and focused study is warranted.

Preliminary results of [99mTc]OKT3 scintigraphy to evaluate acute rejection in renal transplants.

Allograft rejection can be classified as humoral or cellular mechanisms. Accurate diagnosis of acute rejection remains a formidable challenge in renal transplantation. The need to avoid unnecessary immunosuppressive therapy to treat this complication has led to a continued search for improved diagnostic methods to evaluate and identify postoperative episodes. Here we evaluated the use of [(99m)Tc]OKT3 scintigraphy to diagnose acute rejection in renal transplants. Among 22 patients undergoing renal transplant, we observed an increased [(99m)Tc]OKT3 kidney uptake with the passage of time in patients with rejecting allografts. These findings agreed with those of biopsies. We suggest the [(99m)Tc]OKT3 scans may be useful for the monitoring of renal transplants to detect acute rejection.

Fungemia due to Fusarium sacchari in an immunosuppressed patient.

The fungus Fusarium sacchari was isolated repeatedly from the blood of an immunosuppressed host. The infection was treated successfully with a small dose of amphotericin B. The strain was resistant to this antifungal in vitro. MICs and minimum fungicidal concentrations of six antifungals for the clinical isolate are provided. To our knowledge, this is the first report involving this fungus in a case of fungemia.

[Idiopathic lumbosacral plexus neuropathy in child. Case report]. / Neuropatia idiopática do plexo lombossacro em criança. Relato de caso.

We describe a lumbosacral plexus neuropathy case in childhood in which detailed investigation, including electromyography and magnetic resonance imaging, was normal. Muscle biopsy showed mild denervation. No underlying condition was detected. The patient presented with pain, weakness and light atrophy in left lower limb, reduced reflex at the ankle, loss of the quadriceps reflex and paresthesy in involved limb. Recovery after one year was almost complete, with persistent slight weakness and atrophy.