Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids.

BACKGROUND: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2×107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×107 CMs. CONCLUSIONS: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.

Efficacy of exon-skipping therapy for DMD cardiomyopathy with mutations in actin binding domain 1.

Exon-skipping therapy is a promising treatment strategy for Duchenne muscular dystrophy (DMD), which is caused by loss-of-function mutations in the DMD gene encoding dystrophin, leading to progressive cardiomyopathy. In-frame deletion of exons 3-9 (Δ3-9), manifesting a very mild clinical phenotype, is a potential targeted reading frame for exon-skipping by targeting actin-binding domain 1 (ABD1); however, the efficacy of this approach for DMD cardiomyopathy remains uncertain. In this study, we compared three isogenic human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) expressing Δ3-9, frameshifting Δ3-7, or intact DMD. RNA sequencing revealed a resemblance in the expression patterns of mechano-transduction-related genes between Δ3-9 and wild-type samples. Furthermore, we observed similar electrophysiological properties between Δ3-9 and wild-type hiPSC-CMs; Δ3-7 hiPSC-CMs showed electrophysiological alterations with accelerated CaMKII activation. Consistently, Δ3-9 hiPSC-CMs expressed substantial internally truncated dystrophin protein, resulting in maintaining F-actin binding and desmin retention. Antisense oligonucleotides targeting exon 8 efficiently induced skipping exons 8-9 to restore functional dystrophin and electrophysiological parameters in Δ3-7 hiPSC-CMs, bringing the cell characteristics closer to those of Δ3-9 hiPSC-CMs. Collectively, exon-skipping targeting ABD1 to convert the reading frame to Δ3-9 may become a promising therapy for DMD cardiomyopathy.

Mature human induced pluripotent stem cell-derived cardiomyocytes promote angiogenesis through alpha-B crystallin.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat heart diseases; however, the optimal maturity of hiPSC-CMs for effective regenerative medicine remains unclear. We aimed to investigate the benefits of long-term cultured mature hiPSC-CMs in injured rat hearts. METHODS: Cardiomyocytes were differentiated from hiPSCs via monolayer culturing, and the cells were harvested on day 28 or 56 (D28-CMs or D56-CMs, respectively) after differentiation. We transplanted D28-CMs or D56-CMs into the hearts of rat myocardial infarction models and examined cell retention and engraftment via in vivo bioluminescence imaging and histological analysis. We performed transcriptomic sequencing analysis to elucidate the genetic profiles before and after hiPSC-CM transplantation. RESULTS: Upregulated expression of mature sarcomere genes in vitro was observed in D56-CMs compared with D28-CMs. In vivo bioluminescence imaging studies revealed increased bioluminescence intensity of D56-CMs at 8 and 12 weeks post-transplantation. Histological and immunohistochemical analyses showed that D56-CMs promoted engraftment and maturation in the graft area at 12 weeks post-transplantation. Notably, D56-CMs consistently promoted microvessel formation in the graft area from 1 to 12 weeks post-transplantation. Transcriptomic sequencing analysis revealed that compared with the engrafted D28-CMs, the engrafted D56-CMs enriched genes related to blood vessel regulation at 12 weeks post-transplantation. As shown by transcriptomic and western blot analyses, the expression of a small heat shock protein, alpha-B crystallin (CRYAB), was significantly upregulated in D56-CMs compared with D28-CMs. Endothelial cell migration was inhibited by small interfering RNA-mediated knockdown of CRYAB when co-cultured with D56-CMs in vitro. Furthermore, CRYAB overexpression enhanced angiogenesis in the D28-CM grafts at 4 weeks post-transplantation. CONCLUSIONS: Long-term cultured mature hiPSC-CMs promoted engraftment, maturation and angiogenesis post-transplantation in infarcted rat hearts. CRYAB, which was highly expressed in D56-CMs, was identified as an angiogenic factor from mature hiPSC-CMs. This study revealed the benefits of long-term culture, which may enhance the therapeutic potential of hiPSC-CMs.

Cardiac Regeneration Using Pluripotent Stem Cells and Controlling Immune Responses.

Pluripotent stem cell (PSC)-derived cardiomyocytes are a promising source of cells in myocardial regeneration therapy for end-stage heart failure. Because most previous reports have focussed on xenotransplantation models using immunocompromised animals, studies on immune rejection in allogeneic transplantation models are needed for preclinical and clinical applications. Human leukocyte antigen (HLA) plays an important role in allogeneic transplantation, and cell bank projects are currently underway worldwide to stock induced pluripotent stem cells (iPSCs) generated from healthy individuals with homozygous HLA haplotypes. However, it is difficult to stock iPSCs that match the entire population in these cell banks; thus, several groups have produced hypoimmunogenic PSCs by knocking out HLA. These HLA-knockout PSCs were able to avoid rejection by T cells but still suffered rejection by natural killer (NK) cells caused by 'missing self-recognition'. Recent studies have attempted to generate hypoimmunogenic PSCs with gene editing to inhibit NK cell activation. Regenerative medicine using autologous iPSCs can be an ideal transplantation therapy, but, currently, there are major hurdles to its practical application. Hopefully, further research will resolve these issues. This review provides an overview of the current understanding and progress in this field.

Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration.

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.

Central extracorporeal membrane oxygenation with left-ventricular vent for fulminant myocarditis: a retrospective study.

PURPOSE: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. METHODS: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. RESULTS: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. CONCLUSIONS: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies.

Association between postoperative delirium and heart rate variability in the intensive care unit and readmissions and mortality in elderly patients with cardiovascular surgery.

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery.

[Successful Removal of Intrapericardial Needle using Needle Guidance System].

A 41-year-old man stuck himself with needle through his pericardium during suicide attempt. Chest radiography revealed several needles in the bilateral lung fields as well. Computed tomography (CT) and echocardiography showed massive pericardial effusion and a needle penetrating the pericardium. The patient was initially treated conservatively, including pericardial drainage, and, seven days later, we removed the needle using syngo Needle Guidance in hybrid operating room. The length of skin incision was only 2 cm, and the postoperative course was uneventful. No previous studies, to the best of our knowledge, have shown the use of syngo Needle Guidance to remove a needle in the pericardial cavity. This surgical procedure is minimally invasive for the patient.

Intimal Sarcoma after Endovascular Abdominal Aortic Aneurysm Repair.

A 72-year-old man, who was treated 10 years earlier with endovascular aortic aneurysm repair, presented with a fever. Considering the concern of stent graft infection, the patient was treated with antibiotics, but his condition did not improve. He underwent stent graft resection and reconstruction with a Dacron graft. Pathological analysis of the aortic wall and computed tomography revealed recurrent intimal sarcoma, and the patient underwent resurgery. During follow-up, he underwent two additional resections for local recurrence, but he died 17 months later. Our results suggest that intimal sarcoma should be considered during the follow-up after endovascular aortic aneurysm repair.

Decreased activities of daily living at discharge predict mortality and readmission in elderly patients after cardiac and aortic surgery: A retrospective cohort study.

ABSTRACT: Recently, activities of daily living (ADL) were identified as a prognostic factor among elderly patients with heart disease; however, a specific association between ADL and prognosis after cardiac and aortic surgery is not well established. We aimed to clarify the impact of ADL capacity at discharge on prognosis in elderly patients after cardiac and aortic surgery.This retrospective cohort study included 171 elderly patients who underwent open operation for cardiovascular disease in a single center (median age: 74 years; men: 70%). We used the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to the BI at discharge, indicating a high (BI ≥ 85) or low (BI < 85) ADL status. All-cause mortality and unplanned readmission events were observed after discharge.Thirteen all-cause mortality and 44 all-cause unplanned readmission events occurred during the median follow-up of 365 days. Using Kaplan-Meier analysis, a low ADL status was determined to be significantly associated with all-cause mortality and unplanned readmission. In the multivariable Cox proportional hazard models, a low ADL status was an independent predictor of all-cause mortality and unplanned readmission after adjusting for age, sex, length of hospital stay, and other variables (including preoperative status, surgical parameter, and postoperative course).A low ADL status at discharge predicted all-cause mortality and unplanned readmission in elderly patients after cardiac and aortic surgery. A comprehensive approach from the time of admission to postdischarge to improve ADL capacity in elderly patients undergoing cardiac and aortic surgery may improve patient outcomes.

Transplantation of Pluripotent Stem Cell-Derived Cardiomyocytes into a Myocardial Infarction Model of Cynomolgus Monkey.

Recent evidence has provided exciting proof of concepts for the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) for cardiac repair; however, large animal studies, which better reflect human disease, are required for clinical application. Here, we describe how to create myocardial infarction in cynomolgus monkey followed by transplantation of PSC-CMs. This method ensures the establishment of a myocardial infarction model and enables reliable PSC-CM transplantation.

Strategies to improve outcomes for acute type A aortic dissection with cerebral malperfusion.

OBJECTIVES: We aimed to identify predictors of postoperative permanent neurological deficits (PNDs) and evaluate the early management of cerebral perfusion in patients undergoing surgical repair of acute type A aortic dissection with cerebral malperfusion. METHODS: Between October 2009 and September 2018, a total of 197 patients with acute type A aortic dissection underwent aortic replacement. Of these, 42 (21.3%) patients had an imaging cerebral malperfusion (ICM). ICM was assessed preoperatively, which also revealed whether dissected supra-aortic branch vessels were occluded or narrowed by a thrombosed false lumen. After September 2017, early reperfusion and extra-anatomic revascularization were performed in cases with ICM. RESULTS: Hospital mortality rates for cases with ICM were 4.8% (2/42). Before September 2017, PND were observed in 6 patients (54.5%) with preoperative neurological symptoms (n = 11), and 7 patients (33.3%) without neurological symptoms (n = 21) in patients with ICM. Occlusion or severe stenosis of supra-aortic branch vessels (odds ratio, 7.66; P < 0.001), regardless of preoperative clinical neurological symptoms, was a risk factor for PND. After September 2017, 7 of 10 patients with ICM underwent early reperfusion and extra-anatomic revascularization. PND did not occur in any of these 7 patients. CONCLUSIONS: Occlusion or severe stenosis of supra-aortic branch vessels is a predictor of PND risk in patients undergoing surgery for acute type A aortic dissection. Early reperfusion and extra-anatomic revascularization may reduce the risk of neurological complications in patients with ICM, with or without neurological symptoms.

Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo.

Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect "heart regeneration", replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.

Skeletal muscle quality affects patient outcomes in acute type A aortic dissection.

OBJECTIVES: Although skeletal muscle quantity is linked to surgical outcomes, quality remains unexamined. In this study, we evaluated whether skeletal muscle quality and quantity could predict surgical outcomes in acute type A aortic dissection (ATAAD). METHODS: Skeletal muscle quality and quantity were evaluated using computed tomography (CT) values and the psoas muscle mass index, respectively. From May 2004 to December 2017, 324 ATAAD patients underwent aortic replacement after CT scans and psoas muscle mass index measurements. Patients were grouped into intramuscular fat (IMF; n = 55) and non-IMF (n = 269) deposition groups. RESULTS: The mean ages of the patients were 72.3 ± 9.7 and 66.8 ± 12.1 years (P = 0.002), and hospital mortality rates were 3.6% (2/55) and 7.4% (20/269; P = 0.393) for IMF and non-IMF deposition groups, respectively. IMF deposition was a risk factor for a deterioration in activities of daily living at discharge by multivariable analysis [odds ratio 0.33, 95% confidence interval (CI) 0.16-0.69; P = 0.003]. The mean follow-up was 43.9 ± 36.8 months. The 5-year survival was significantly worse for the IMF deposition group (IMF 73.8% vs non-IMF 88.2%; P = 0.010). The multivariable Cox proportional hazard analysis showed that IMF deposition significantly predicted poor survival (hazard ratio 3.26, 95% CI 1.47-7.24; P = 0.004), unlike psoas muscle mass index and age. CONCLUSIONS: Skeletal muscle quality, defined by IMF deposition, was an independent predictor of overall survival and postoperative activities of daily living dependence risk in patients undergoing surgery for ATAAD. Thus, IMF deposition may be an additional risk factor for estimating late outcomes of ATAAD surgery.

Impact of Frailty on Outcomes in Acute Type A Aortic Dissection.

BACKGROUND: Although frailty is used to predict morbidity and mortality, its effect on the outcomes of acute type A aortic dissection has not been examined. Therefore, the objective of this study was to evaluate the role of frailty in predicting postoperative morbidity and mortality of patients with acute type A aortic dissection. METHODS: A retrospective analysis of a prospectively maintained database was undertaken for all patients (n = 310) undergoing aortic surgery between May 2004 and March 2017. Frailty was evaluated using an index consisting of age more than 70 years, body mass index less than 18.5 kg/m2, serum creatinine greater than 1.2 mg/dL, anemia, history of stroke, hypoalbuminemia, and the psoas muscle area index. One point was given for each criterion met, for a frailty score between 0 and 7. Frailty was defined as a score of 3 or more. RESULTS: Of all patients, 106 (34.2%) were defined as frail. Inhospital mortality rates of frail versus nonfrail patients were not significantly different (10.4% versus 8.3%, respectively; p = 0.54). Incidences of postoperative major morbidities without reexploration for bleeding were also not statistically different. Five-year survival rates were significantly worse for frail patients than for nonfrail patients (57.7% versus 85.1%, respectively; p = 0.0001). A frailty score of 3 or greater was associated with late mortality, and long-term outcomes were clearly stratified by frailty score. CONCLUSIONS: Frailty, as defined using a seven-component frailty index, can serve as an independent predictor of the risk of late mortality for patients undergoing surgery for acute type A aortic dissection. Such frailty markers, all of which are easily assessed preoperatively, may provide valuable information for patient counseling and risk stratification before aortic surgery.

Impact of extracellular matrix on engraftment and maturation of pluripotent stem cell-derived cardiomyocytes in a rat myocardial infarct model.

Pluripotent stem cell-derived cardiomyocytes show great promise in regenerating the heart after myocardial infarction; however, several uncertainties exist that must be addressed before clinical trials. One practical issue is graft survival following transplantation. Although a pro-survival cocktail with Matrigel has been shown to enhance graft survival, the use of Matrigel may not be clinically feasible. The purpose of this study was to test whether a hyaluronan-based hydrogel, HyStem, could be a substitute for Matrigel. Human induced pluripotent stem cell-derived cardiomyocytes diluted with HyStem alone, HyStem plus pro-survival factors, or a pro-survival cocktail with Matrigel (PSC/MG), were transplanted into a rat model of acute myocardial infarction. Histological analysis at 4 weeks post transplantation revealed that, among the three groups, recipients of PSC/MG showed the largest graft size. Additionally, the grafted cardiomyocytes in the recipients of PSC/MG had a more matured phenotype compared to those in the other two groups. These findings suggest that further studies will be required to enhance not only graft size, but also the maturation of grafted cardiomyocytes.

Recent Progress Using Pluripotent Stem Cells for Cardiac Regenerative Therapy.

Pluripotent stem cells (PSCs) have gained interest for cell-based regenerative therapies because of their capacity to differentiate into most somatic cell types, including cardiomyocytes. Remarkable progress in the generation of PSC-derived cardiomyocytes has been made in this decade, and recent preclinical transplantation studies using various animal models have provided proof-of-principle for their use in heart regeneration. However, several obstacles preclude their effective and safe clinical application for cardiac repair, including the need for approaches that prevent tumorigenesis, arrhythmogenesis, and immune rejection. In this review, we focus on recent progress in the field of PSC-based cardiac regenerative therapy, including the remaining hurdles and potential approaches to circumventing them.

Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.

Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.

Pericoronary pseudotumor caused by helicobacter cinaedi.

Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We here report a case of a pericoronary tumor-like lesion surrounding the right coronary artery in a 39-year-old man who presented with fever and chest pain. Although clarithromycin was administered for 1 week, his fever persisted. Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary artery. After administration of ceftriaxone, the tumor-like lesion diminished in size according to meticulous computed tomography examinations. We therefore concluded that it was caused by H. cinaedi infection. The patient has been followed up closely for 1 year and remains asymptomatic.

Eradication and reinfection of human papillomavirus after photodynamic therapy for cervical intraepithelial neoplasia.

BACKGROUND: Photodynamic therapy (PDT) has been proven to be a promising therapeutic modality for selected dysplasias and malignancies in a variety of organs. We assessed the effectiveness of PDT for treating cervical intraepithelial neoplasia (CIN) by cytological and histological examinations and investigated its impact on human papillomavirus (HPV) infection. METHODS: A series of 31 patients with CIN (2 with CIN2, 29 with CIN3) were given polyhematoporphyrin ether/ester (PHE) 2 mg/kg IV. After 60 h their cervices were exposed to a 630-nm YAG-OPO laser. HPV-DNA extracted from cervical smears was amplified by the polymerase chain reaction and typed for HPV using restriction fragment length polymorphism. RESULTS: At 3 months after PDT, cytology and directed biopsy of the cervix revealed regression of the disease in 28 [complete remission (CR) rate 90%] of 31 patients, and HPV-DNA could be no longer detected in the cervical smears of 22 (76%) of 29 HPV-positive patients. After 12 months, all 31 patients had achieved a CR on biopsy, although HPV-DNA was still present in the cervical smears of 6 patients. The types of HPV-DNA detected 12 months after PDT were different from those seen before PDT in each of the 6 patients, suggesting that they might be reinfected with other HPV types after PDT. CONCLUSION: PDT is effective not only in improving the cytological and histological measures when treating CIN but also for eradicating cervical HPV.