Long-term Outcome of Endovascular Treatment for Mycotic Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Endovascular repair (EVAR) of mycotic aortic aneurysm (MAA) has become an alternative treatment for high risk patients. The aim of this study was to evaluate long-term survival and outcomes. METHODS: Retrospective analysis of 40 consecutive patients with MAAs undergoing EVAR and subsequent intravenous antibiotic treatment between September 2009 and April 2015. Follow-up was truncated on 30 April 2015. Uni- and multivariate logistic regression were used to assess risk factors of adverse outcomes. Cumulative survival was calculated using the Kaplan-Meier method. RESULTS: Median age at repair was 73 years (range 48-88 years) and 31 (77%) were men. Eleven (27%) patients were infected with Salmonella, 12 (30%) with non-Salmonella species, and 17 (42%) had negative cultures. Anatomical locations included the aortic arch/thoracic area in 10 (25%), the paravisceral area in seven (17%), and the infrarenal area in 23 (57%). Ten (25%) patients presented with aneurysm rupture and underwent emergency repair. Median follow-up was 25 months (range 1-69 months). Cumulative 1 and 5 year survival rates were 71% and 53%, respectively. Persistent or recurrent infection occurred in 20% (n = 8). Patients with persistent infection were treated with long-term medical therapy, but all died (75%; n = 6) within 6 months of repair. No survival difference was found between patients with or without Salmonella infections. However, there was a trend toward better survival in culture negative patients. CONCLUSION: EVAR of MAA is an acceptable alternative treatment of MAA. However, persistent infection after endovascular treatment does occur and is often fatal without surgical treatment.

Quasiparticle dynamics and phonon softening in FeSe superconductors.

Quasiparticle dynamics of FeSe single crystals revealed by dual-color transient reflectivity measurements (ΔR/R) provides unprecedented information on Fe-based superconductors. The amplitude of the fast component in ΔR/R clearly gives a competing scenario between spin fluctuations and superconductivity. Together with the transport measurements, the relaxation time analysis further exhibits anomalous changes at 90 and 230 K. The former manifests a structure phase transition as well as the associated phonon softening. The latter suggests a previously overlooked phase transition or crossover in FeSe. The electron-phonon coupling constant λ is found to be 0.16, identical to the value of theoretical calculations. Such a small λ demonstrates an unconventional origin of superconductivity in FeSe.

High-glucose environment reduces human ß-defensin-2 expression in human keratinocytes: implications for poor diabetic wound healing.

BACKGROUND: Wound healing is a dynamic and complicated process in which inflammation, re-epithelialization and angiogenesis play important roles. Intriguingly, all three processes have been found to be defective during diabetic wound healing conditions. One common denominator associated with regulation of these events is human ß-defensin-2 (hBD2). It has been shown that skin wounding induces cutaneous hBD2 expression, and diabetic wounds have been associated with inadequate hBD expression. OBJECTIVES: The current study was launched to explore the effects of a high-glucose environment on cultured human keratinocytes. METHODS: Human keratinocytes were exposed to indicated culture conditions. The mRNA and protein levels of hBD2 were determined, and activation of relevant pathways was evaluated. The small interference RNA approach was used to validate the functional role of the proposed pathway on hBD2 expression. RESULTS: We showed that high-glucose cultivated keratinocytes expressed reduced levels of hBD2 and phosphorylated signal transducer and activator of transcription (pSTAT)-1 constitutively. In addition, pSTAT-1 signalling is critically involved in hBD2 expression. Formation of advanced glycation endproducts, a direct consequence of a high-glucose environment, involves constitutive downregulation of pSTAT-1 and hBD2. The addition of interleukin-1ß, an important cytokine during the cutaneous wound healing process, enabled the upregulation of hBD2 expression of both normal- and high-glucose cultivated keratinocytes, but the absolute levels of hBD2 were still significantly lower in the high-glucose-treated group. CONCLUSIONS: As hBD2 plays multifaceted roles during the wound healing process, the inadequate expression of hBD2 during diabetic conditions contributes to impaired wound healing.

An osmosensing signal transduction pathway in mammalian cells.

The osmotic balance between the cytoplasmic and extracellular compartments of cells is critical for the control of cell volume. A mammalian protein kinase, Jnk, which is a distant relative of the mitogen-activated protein kinase group, was activated by phosphorylation on threonine and tyrosine in osmotically shocked cells. The activation of Jnk may be relevant to the biological response to osmotic shock because the expression of human Jnk in the yeast Saccharomyces cerevisiae rescued a defect in growth on hyper-osmolar media. These data indicate that related protein kinases may mediate osmosensing signal transduction in yeast and mammalian cells.

Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.

Mammalian mitogen-activated protein (MAP) kinases include extracellular signal-regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38 subgroups. These MAP kinase isoforms are activated by dual phosphorylation on threonine and tyrosine. Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. These MKK isoforms did not activate the ERK subgroup of MAP kinases, but MKK4 did activate JNK. These data demonstrate that the activators of p38 (MKK3 and MKK4), JNK (MKK4), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.

Binding of zinc finger protein ZPR1 to the epidermal growth factor receptor.

ZPR1 is a zinc finger protein that binds to the cytoplasmic tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Deletion analysis demonstrated that this binding interaction is mediated by the zinc fingers of ZPR1 and subdomains X and XI of the EGFR tyrosine kinase. Treatment of mammalian cells with EGF caused decreased binding of ZPR1 to the EGFR and the accumulation of ZPR1 in the nucleus. The effect of EGF to regulate ZPR1 binding is dependent on tyrosine phosphorylation of the EGFR. ZPR1 therefore represents a prototype for a class of molecule that binds to the EGFR and is released from the receptor after activation.

The significance of endograft geometry on the incidence of intraprosthetic thrombus deposits after abdominal endovascular grafting.

OBJECTIVES: To examine the incidence and risk factors of intraprosthetic thrombotic deposits in abdominal aortic endografts. METHODS: The clinical records of 51 patients (44 males; mean age 76.3 years, range: 63-90 years) with abdominal aortic aneurysm treated with transfemoral implantation of bifurcated stent graft between the years 2002 and 2008 were retrospectively reviewed. Patients underwent three-phase helical computed tomographic (CT) examinations at 1-, 3-, 6- and 12-month intervals and then annually. The formation of intraprosthetic thrombus associated with use of anti-platelet, preoperative mural thrombus in the aneurysm, ratio of cross-sectional area between the mainbody and bilateral limb grafts and length of mainbody were evaluated. RESULTS: Over a 10-month mean follow-up, intraluminal deposits of thrombotic material were observed in eight of 51 patients (15.6%, 95% confidence interval: 8.2-28). The first signs of thrombus formation occurred on average 9.8 months after endografting (range: 1-24 months). Intraprosthetic thrombotic deposits was not related to preoperative mural thrombus formation (p=0.38) or postoperative anti-platelet or anticoagulation medication (p=0.40). However, it was significantly related to the ratio of the cross-sectional area between the mainbody and the bilateral limb grafts and the length of mainbody (p=0.04 and p=0.01). There were three graft limbs occlusion owing to kinking with no intraprosthetic thrombus detected on CT scans taken prior to occlusion. One patient developed distal left proximal superior femoral artery embolisation 4 months after detectable intraprosthetic mainbody thrombus in a CT scan follow-up. In no case did the thrombotic deposits clear completely from the prosthesis lumen during follow-up. CONCLUSIONS: This short experience demonstrates that incidentally found thrombotic deposits in abdominal aortic endografts are common. The deposition of thrombus is mostly influenced by the geometry of the aortic stent graft with wider mainbody diameter coupled with smaller limb grafts and longer mainbody graft. Most of these thrombi are clinically silent and require no additional treatment.

Medium-term outcomes in cardiac transplant recipients in a single cardiac transplant center in Taiwan.

This study retrospectively investigated the outcomes of cardiac transplantation in a single medical center in Taiwan. From February 1997 to December 2005, 214 orthotopic cardiac transplantations were performed in our institution. Cumulative survival rates were compared by gender, waiting status, blood type, ischemia time, donor gender, age, and cause of brain death. The cumulative survival rates were significant different among recipient waiting status (P = .0026), blood type (P = .0376), and donor age > 40 years (P = .0260). The others parameters seem to not be different from the cumulative survival rate. There was a strong association between donors > 40 years old and increased postoperative mortality. The age of a marginal donor seemed to be > 40 years in this study.

Heart transplantation under cyclosporine or tacrolimus combined with mycophenolate mofetil or everolimus.

OBJECTIVE: In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT). PATIENTS AND METHODS: From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors > 60 years; cold ischemia times > 6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies > or = 25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies. RESULTS: No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% +/- 18.1%, 89.7% +/- 29.8%, and 81.0% +/- 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% +/- 28.3%, 79.8% +/- 46.0%, and 81.0% +/- 35.5% in groups CE, CM, and TM, respectively. CONCLUSIONS: The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%.

Cardiac arrest after methylprednisolone pulse therapy rescued using extracorporeal membrane oxygenation in patients with acute cardiac rejection: two case reports.

Patients receive methylprednisolone pulse therapy (MPT) when acute cardiac rejection occurs. Although the regimen is generally safe and effective, severe complications occasionally develop. From 1997 to 2007, there were 210 cardiac transplantation procedures performed at our hospital. Among these patients, there were 23 episodes of acute rejection treated with MPT, 10 mg/kg/d. Two patients in our series had cardiac arrest within 36 hours after initiating the therapy. Endomyocardial biopsy specimens showed International Society for Heart Transplantation grade 1B allograft rejection in both cases. Emergent intubation and cardiopulmonary resuscitation were performed. Venoarterial extracorporeal membrane oxygenation (ECMO) was used to rescue the patients. The cardiac function in both patients recovered gradually. Left ventricular ejection fraction increased from 16.2% to 47% in one patient and from 27% to 30% in the other patient. One patient was successfully weaned from ECMO after 2 days of support. The other patient was discharged against medical advice because of hypoxia-related brain death after 3 days. Both patients had a history of tachyarrhythmias before initiation of MPT. Although the relationship between mechanisms of cardiac arrest and MPT is uncertain, the risk of cardiac arrest cannot be overlooked when initiating MPT, especially in patients with a history of tachyarrhythmia. Meanwhile, ECMO can serve as a rescue method if cardiac arrest occurs.

Surgical treatment of mediastinitis after cardiac transplantation.

Mediastinitis is a life-threatening complication among patients undergoing cardiac transplantation. There are conservative and aggressive surgical treatments. From October 1987 to October 2007, we reviewed the clinical records of 315 heart transplantations for those four cases with severe mediastinis needing surgical treatment for demographic data, clinical presentation, treatment, and outcome. Conservative therapy, such as sternal debridement without muscle flap closure and closed local irrigation with drainage, was performed in two cases. The other two patients needed aggressive surgical treatment with muscle flap or omental flap performed. Only one transplant recipient with severe mediastinis had undergone previous sternotomy before cardiac transplantation. The organisms were methicillin-resistant Staphylococcus aureus in three and Aspergillus fumigatus in one case. The one subject who received conservative therapy without a flap died. The other two with muscle flap and omental flap survived. Cardiac recipients survived if there was aggressive surgical treatment for severe mediastinitis. Meanwhile, we recommend prolonged aggressive antibiotic therapy and reduced immunotherapy.

Tuberculosis after heart transplantation: twenty years of experience in a single center in Taiwan.

The incidence of tuberculosis is slightly higher among heart transplantation cases than in the general population in Taiwan. Tuberculosis shows a high mortality rate ranging from 22% to 31% in transplant recipients. From October 1987 to October 2007, we performed 315 heart transplantations. Clinical records were reviewed for demographic data, clinical presentation, treatment, and outcome. Tuberculosis was diagnosed by cultures of any body sample in association with compatible symptoms and signs. Mortality was related to tuberculosis if there was evidence of active tuberculosis at the time of death and no other etiology accounted for death. Ten patients who had received heart transplants were diagnosed as tuberculosis. There were seven pulmonary lesions and seven extrapulmonary lesions. Treatment consisted of isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, ciprofloxacin, and levofloxacin. Seven patients completed the antituberculosis treatment: the median treatment duration was 1 year. Three patients developed hepatitis. There was no tuberculosis-related mortality. Ten out of a total of 315 patients (3.17%) represented a tuberculosis rate higher than that reported for the general Taiwan population (67/100,000). This high mortality of infection may be completely treated by a combination of at least three drugs except pyrzinamide because of side effects and tolerance.

A conserved p38 mitogen-activated protein kinase pathway regulates Drosophila immunity gene expression.

Accumulating evidence suggests that the insect and mammalian innate immune response is mediated by homologous regulatory components. Proinflammatory cytokines and bacterial lipopolysaccharide stimulate mammalian immunity by activating transcription factors such as NF-kappaB and AP-1. One of the responses evoked by these stimuli is the initiation of a kinase cascade that leads to the phosphorylation of p38 mitogen-activated protein (MAP) kinase on Thr and Tyr within the motif Thr-Gly-Tyr, which is located within subdomain VIII. We have investigated the possible involvement of the p38 MAP kinase pathway in the Drosophila immune response. Two genes that are highly homologous to the mammalian p38 MAP kinase were molecularly cloned and characterized. Furthermore, genes that encode two novel Drosophila MAP kinase kinases, D-MKK3 and D-MKK4, were identified. D-MKK3 is an efficient activator of both Drosophila p38 MAP kinases, while D-MKK4 is an activator of D-JNK but not D-p38. These data establish that Drosophila indeed possesses a conserved p38 MAP kinase signaling pathway. We have examined the role of the D-p38 MAP kinases in the regulation of insect immunity. The results revealed that one of the functions of D-p38 is to attenuate antimicrobial peptide gene expression following exposure to lipopolysaccharide.

Transforming growth factor beta 1 suppresses genomic instability independent of a G1 arrest, p53, and Rb.

Alterations in expression of or responsiveness to transforming growth factor beta (TGF-beta) are frequently found in human and animal epithelial cancers and are though to be important for loss of growth control in the neoplastic cell. We show here that keratinocyte cell lines from mice with a targeted deletion of the TGF-beta 1 gene have significantly increased frequencies of gene amplification in response to the drug N-phosphonoacetyl-L-aspartate (PALA) compared to TGF-beta 1-expressing control keratinocyte cell lines. In contrast to the control lines, the PALA-mediated G1 arrest did not occur in the TGF-beta 1 null keratinocytes despite the presence of wild-type p53 in both genotypes. Exogenous TGF-beta 1 suppresses gene amplification in the null keratinocytes at concentrations that do not cause a G1 growth arrest and in human tumor cell lines that are insensitive to TGF-beta 1-mediated growth inhibition. The pathway of TGF-beta 1 suppression is independent of the p53 and Rb genes, but requires an intact TGF-beta type II receptor. These studies reveal a novel TGF-beta-mediated pathway regulating genomic stability and suggest that defects in TGF-beta signaling may have profound effects on tumor progression independent of cell proliferation.

Higher serum uric acid level increases risk of prehypertension in subjects with normal glucose tolerance, but not pre-diabetes and diabetes.

Although the association between serum uric acid (SUA) levels and prehypertension has been reported in previous studies, it is unknown whether their relationship is similar in subjects with diabetes, pre-diabetes and normal glucose tolerance (NGT). This study thus aimed to investigate the relationship between SUA and prehypertension in subjects with different glycemic status, including NGT, pre-diabetes and diabetes. A total of 12 010 participants were included after excluding subjects with blood pressure ⩾140/90 mm Hg, history of hypertension, leukaemia, lymphoma, hypothyroidism, medication for hypertension and hyperuricemia and missing data. Subjects were divided into four groups based on SUA quartiles (male Q1: ⩽345.0, Q2: 345.0-392.6, Q3: 392.6-440.2, Q4: ⩾440.2 µmol l(-1) and female Q1: ⩽249.8, Q2: 249.8-285.5, Q3: 285.5-333.1, Q4: ⩾333.1 µmol l(-1)). Diabetes, pre-diabetes and NGT were assessed according to the 2010 American Diabetes Association diagnostic criteria. Normotension and prehypertension were defined according to the JNC-7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) criteria. The SUA was significantly higher in prehypertensive subjects as compared with normotensive subjects. SUA, as a continuous variable, was positively associated with prehypertension in subjects with NGT but not pre-diabetes and diabetes. Besides, NGT subjects with the highest quartile of SUA exhibited a higher risk of prehypertension after adjustment for other confounding factors. In pre-diabetes and diabetes groups, none of SUA quartiles was significantly related to prehypertension. SUA was significantly associated with an increased risk of prehypertension in subjects with NGT but insignificantly in subjects with pre-diabetes and diabetes.

Case Series: Heart Transplantation After Fontan Operation-Single-Center Experience.

BACKGROUND: Fontan failure (FF) occurs rarely. In patients with Fontan failure, heart transplantation is believed to be the most effective therapy. We review our experience in heart transplantations after the Fontan operation. METHODS: From July 1987 to December 2014, 4 of 513 patients underwent orthotopic heart transplantation (OHT). Among them, 4 were due to FF. We reviewed these 4 cases via retrospective chart review. Clinical history, laboratory data, surgical technique, perioperative variables, and outcomes of long-term follow-up are presented herein. The primary outcomes were hospital mortality, 1-year-survival rate, and 4-year-survival rate. The secondary outcome is the improvement in patients with protein-losing enteropathy. RESULTS: The hospital mortality rate was 0% in the 4 FF patients receiving OHT. No surgically related hemorrhage or infection was observed. The 1-year-survival rate was 100% (n = 4) and the 4-year-survival rate 50% (n = 2). One patient died of posttransplantation lymphoproliferative disorder. Hypoalbuminemia improved in 1 of 3 patients 4 months after OHT. CONCLUSIONS: Despite technical challenges, heart transplantation can be performed successfully in patients with Fontan operation. However, protein-losing enteropathy might not be resolved quickly after heart transplantation.

Malignancy After Heart Transplantation Under Everolimus Versus Mycophenolate Mofetil Immunosuppression.

BACKGROUND: With advances in immunosuppressive therapy, heart transplantation is currently recommended as the only established surgical treatment for refractory heart failure. However, chronic immunosuppression increases the risk for malignancy. Everolimus (EVR) is a potent mammalian target of rapamycin inhibitor that is used after transplantation and to treat advanced malignancies, as we have done in Taiwan after heart transplantation since 2004. Mycophenolate mofetil (MMF) and EVR are frequently used as cell-cycle inhibitors to optimize post-transplantation outcomes. METHODS: We retrospectively analyzed the characteristics and outcomes of 454 patients who received either MMF (n = 232) or EVR (n = 222) after heart transplantation at the National Taiwan University Hospital from March 1, 1990, to March 1, 2015. Patient characteristics and Kaplan-Meier survival curves were compared between groups. RESULTS: During a median follow-up of 69.2 months, malignancy was diagnosed in 27 patients receiving MMF (n = 23) or EVR (n = 4). There was a significant difference in malignancy risk between groups (9.91% vs 1.80%, P = .001). The most common malignancies were non-Hodgkin lymphoma, skin cancers, and lung squamous cell carcinoma. The 2-year overall survival after malignancy was 50% in the EVR group and 47% in the MMF group (P = .745). CONCLUSIONS: EVR treatment after heart transplant is associated with a lower risk of malignancy than is MMF treatment. The 2-year survival rate after malignancy was similar between EVR and MMF groups.

Low Incidence of Malignancy After Heart Transplantation in Taiwan.

BACKGROUND: Malignancy is the leading cause of death in Taiwan. The risk of malignancy is higher in heart transplant recipients than in the general population. We reviewed the malignancy incidence among the patients who underwent heart transplantation (HT) at the National Taiwan University Hospital (NTUH) during the past 28 years. We found that the incidence of malignancy is low in Taiwan and that the pattern of malignancy is different from that in the Western population. METHODS: From July 1987 to March 2015, 518 patients underwent HT at NTUH. Forty-four patients who died within 1 month after transplantation were excluded from this study. Thus, a total of 476 patients were enrolled in this study. There were 393 male and 83 female patients, with a mean age of 45 years at transplantation. The major indications for HT were dilated cardiomyopathy (52%) and ischemic cardiomyopathy (33%). After HT, all patients received triple immunosuppressive therapy, including a calcineurin inhibitor (cyclosporine or tacrolimus), cell-cycle inhibitor (azathioprine, mycophenolate mofetil, or everolimus), and steroid. After 1995, induction with rabbit anti-human thymocyte globulin was routinely performed. Survival was estimated by means of the Kaplan-Meier method. RESULTS: Twenty-seven patients without pre-transplantation malignancy developed malignancies after HT. The median survival time (MST) of these 27 HT patients was 76.8 months. After malignancy was diagnosed, the overall MST was 20.7 months. The 3- and 5-year overall survival rates were 44% and 27%, respectively. Twenty-one patients (77.8%) died, 10 of them because of cancer. The most common malignancy was non-Hodgkin lymphoma (n = 6), followed by skin cancer (including 2 keratoacanthomas, 2 squamous cell carcinomas, and 1 basal cell carcinoma; n = 5) and lung squamous cell carcinoma (n = 3). The univariate analysis identified cancer stage (P = .044) and comorbidity (P = .002) as factors associated with poor malignancy survival. In the multivariate analysis, comorbidity was an independent prognostic factor for greater risk of death because of post-transplantation malignancy (P = .002). CONCLUSIONS: In Taiwan, the risk of malignancy after HT is low (5.7%), as is the incidence of skin cancer. The most common malignancy was non-Hodgkin lymphoma, followed by skin cancer and lung cancer. Comorbidity was an independent factor for overall survival in cancer patients who previously underwent HT.

Surveillance of Immunosuppression During Pregnancy After Heart Transplantation: Case Report.

BACKGROUND: Transplantation and immunosuppressive drugs are major limitations to the success of pregnancy. In 1988, the first pregnancy after a heart transplant was reported, which has given female recipients the hope to give birth. During pregnancy, physiologic changes with increased blood volume and hemodilution may influence blood drug level. CASE REPORT: We reported our experience in monitoring on immunosuppressive drugs for 2 cases. Both of them underwent heart transplantation in 2006 and were 34 and 37 years old at time of pregnancy. For both cases, we frequently monitored the blood level and increased the dosage of immunosuppressive drugs accordingly. Both cases had uneventful pregnancy and delivery to healthy babies at the National Taiwan University Hospital in Taiwan. Their postpartum courses were uneventful as well. CONCLUSIONS: We advocate adjusting the immunosuppressive dosage according to the blood level before pregnancy.

Successful management of a quadruplet pregnancy. A case report.

A quadruplet pregnancy was diagnosed by ultrasound antenatally and managed successfully in a community teaching hospital. The patient was hospitalized at 27 weeks' gestation. She was treated with a high-protein, high-calorie diet. Sonographic follow-up and monitoring of fetal growth were done, glucocorticoids were given to attempt to stimulate fetal pulmonary maturity, and Ritodrine was given orally as a prophylactic. On three occasions intravenous Ritodrine was used to inhibit premature labor. A well-organized delivery plan with interdepartmental cooperation achieved the successful delivery of four babies at approximately 33 weeks.