Colonic Perforation as Initial Presentation of Amyloid Disease: Case Report and Literature Review.

INTRODUCTION: Amyloidosis is an uncommon disease caused by the deposition of amyloid fibrils in tissues. This disease does not usually require surgical intervention, which could be warranted in the presence of complications such as bleeding, obstruction, or perforation. We present a case of primary amyloidosis of the colon in a patient affected by polymyositis who underwent Hartmann's procedure after a spontaneous colonic perforation. After 2 months of well-being, the patient underwent two consecutive surgical procedures for stenosis of the ostomy orifice. AREAS COVERED: A review of the literature has been performed, gathering case reports highlighting the distribution of this disease by age, gender, location, and treatment when available. EXPERT COMMENTARY: Gastrointestinal amyloid disease is a rare condition, and it could be considered among the rare causes of intestinal perforation. Timely surgical management is often necessary.

Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP.

This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.

Criteria for histopathologic diagnosis of aortic disease consensus statement from the SIAPEC-IAP study group of "cardiovascular pathology" in collaboration with the association for Italian cardiovascular pathology.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.

Cognitive functioning and survival in the elderly: the SSADH C538T polymorphism.

The variability of the Succinic Semialdehyde Dehydrogenase (SSADH, or ALDH5A1) gene affects both pathological and normal phenotypes correlated to cognitive function. We tested the association between the C538T polymorphism of the SSADH gene and preservation of cognitive function in the elderly, and its possible effects on survival. A sample from southern Italy (514 subjects; 18-107 years) was screened for C538T variability. We found that, within the 65-85 years age range, the T/T genotype is overrepresented in subjects with impaired cognitive function (MMSE < or = 23) compared to those with conserved cognitive function (MMSE > 23). Furthermore, we found that the T/T genotype affects survival after 65 years of age. In fact, after this age, the survival function of T/T homozygous subjects is lower than that of the others. Given that the enzymatic activity of the protein encoded by allele T is 82.5% of the activity of the protein encoded by allele C, our results suggest that the efficiency of the SSADH enzyme is important for the preservation of cognitive function and survival in the elderly.

Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction.

OBJECTIVES: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. PATIENTS AND DESIGN: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. RESULTS: 65 eligible patients were followed up for 6-193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan-Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class III-IV, sustained ventricular arrhythmias and left atrial size. CONCLUSIONS: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.

Long-term safety and effectiveness of statins for heart transplant recipients in routine clinical practice.

BACKGROUND: Whereas the efficacy of statins after heart transplantation (HT) in controlled study settings has been clearly demonstrated, more extensive data are required on the safety and effectiveness of long-term treatment in routine clinical practice. METHODS: We analyzed the risks and benefits in clinical practice of treatment with statins in all patients who survived HT for at least a month from December 1985 through 2001. RESULTS: During a mean follow-up of 4.8+/-3.8 years, 186 patients were treated with statins (for a median duration [25th to 75th percentile] of 29 [12 to 54] months), while 48 received dietary therapy alone. Patients treated with statins (pravastatin, 48%; atorvastatin, 37%; simvastatin, 14%) presented linearized rates of rhabdomyolisis, myositis, and significant transaminase elevation of 0.37%, 0.74%, and 0.37% per year of treatment, respectively (no fatal event occurred). Low-density lipoprotein decreased after statins by 19% (P<.001). At multivariate analysis, treatment with statins was independently associated with reduced risk of cardiac allograft vasculopathy and overall mortality (P<.001). CONCLUSIONS: Our data provide necessary confirmation of the safety and effectiveness in routine clinical practice of appropriately monitored long-term administration of statins (particularly atorvastatin, pravastatin, and simvastatin) in the chronic post-HT phase. Strict follow-up is needed for HT recipients receiving high doses of statins with/without other medications potentially exacerbating the risk of adverse effects.

Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by gadolinium cardiac magnetic resonance.

OBJECTIVE: To investigate the prevalence and distribution of gadolinium (Gd) enhancement at cardiac magnetic resonance (CMR) imaging in patients with cardiac amyloidosis (CA) and to look for associations with clinical, morphological, and functional features. PATIENTS AND DESIGN: 21 patients with definitely diagnosed CA (nine with immunoglobulin light chain amyloidosis and 12 transthyretin related) underwent Gd-CMR. RESULTS: Gd enhancement was detected in 16 of 21 (76%) patients. Sixty six of 357 (18%) segments were enhanced, more often at the mid ventricular level. Transmural extension of enhancement within each patient significantly correlated with left ventricular (LV) end systolic volume (r = 0.58). The number of enhanced segments correlated with LV end diastolic volume (r = 0.76), end systolic volume (r = 0.6), and left atrial size (r = 0.56). Segments with > 50% extensive transmural enhancement more often were severely hypokinetic or akinetic (p = 0.001). Patients with > 2 enhanced segments had significantly lower 12 lead QRS voltage and Sokolow-Lyon index. No relation was apparent with any other clinical, morphological, functional, or histological characteristics. CONCLUSION: Gd enhancement is common but not universally present in CA, probably due to expansion of infiltrated interstitium. The segmental and transmural distribution of the enhancement is highly variable, and mid-ventricular regions are more often involved. Enhancement appears to be associated with impaired segmental and global contractility and a larger atrium.

Rhinopharynx endoscopy in the diagnosis of chronic otitis media with effusion in infancy.

Chronic otitis media with effusion is an inflammatory process of the mucosa of the middle ear persisting for more than 3 months, being most frequent in infancy, and is correlated with marked tube obstruction. In infancy, the most frequent cause of this obstruction is adenoid hypertrophy and diagnosis, clinical or radiological, is often not confirmed by rhinopharynx fiberendoscopy. Since, in these cases, treatment is often surgical, it is possible that small patients may be submitted, unnecessarily, to adenoidectomy. In collaboration with the Paediatric Clinic, the present study on an infant outpatient population with nasal respiratory difficulty, associated with chronic otitis media with effusion, was, therefore, aimed at standardizing the endoscopic diagnosis of patients with suspected adenoid hypertrophy. Between October and December 2002, 32 consecutive patients, aged between 4 and 11 years, all oral breathers with OME, were sent to our attention from the Paediatric Clinic. All those patients, with indication for adenoidectomy, have been enrolled in the study and submitted to fiberendoscopic examination of the external ear and nose. Nasal respiration was confirmed with active anterior rhinomanometry. Endoscopic evaluation of the rhinopharynx, aimed at assessing adenoid dimensions and their relationship with the auditory tube, has been expressed in four degrees of increasing severity and adenoidectomy was indicated in those cases, classified, by us, as third and fourth degree. In our experience, endoscopic examination of the rhinopharynx has, however, shown that only 9 children (28.2%) presented an absolute need to undergo adenoidectomy since they were carriers of massive adenoid hypertrophy with tubal obstruction and consequent bilateral glue ear (3rd and 4th degree) while, in all other cases (71.8%), the clinical and radiological findings did not correspond to endoscopic data. Diagnostic accuracy that characterizes rhinopharyngeal fiberendoscopy is, therefore, in our opinion, of fundamental importance to avoid these errors, as far as possible, and in establishing an appropriate therapeutic programme.

Fantoni's translaryngeal tracheotomy complications. Personal experience.

Tracheotomy is a surgical procedure which, in conditions of acute respiratory emergency, guarantees an adequate airway through the trachea whereas, in cases of chronic respiratory failure, it is used to improve ventilation through the reduction of the dead respiratory space. Over the last few years, surgical techniques used in tracheotomy have been considerably modified, not only to respond to the needs of clinical indications but also on account of problems related to management of the patient and tracheostomy tube, particularly in the home setting. Besides traditional surgical techniques, in fact, in the Intensive Care Unit, percutaneous dilatative procedures are being used with increasing frequency, in particular, translaryngeal tracheotomy according to Fantoni. The latter, however, according to reports in the literature, has been shown to be followed by a higher peri-operative complication rate (40%) which involves maintenance of good function of the tracheostomy, a condition which is particularly dangerous in the management of patients in the home setting. Personal experience is described in the management of 6 patients submitted to tracheotomy according to Fantoni and in combined home treatment, who, some time after the operation. presented 'embedding' of the tracheostomy tube in the tracheostomy opening. The six patients were treated at home with ventilatory support using automatic ventilation system and were submitted, in our Clinic, to a surgical review with preparation of a tracheotomy according to the conventional method. Our experience showed a particular feature of the difficulty in the management of patients presenting respiratory diseases, submitted to translaryngeal tracheotomy and, thereafter, maintained in combined home treatment: in these subjects, in fact, the presence of the tube, the difficulty in cleaning the peristomial skin, the reduced autonomy from the automatic ventilation system and the frequent coexistence of mucopurulent tracheo-bronchial inflammatory diseases, trigger micro-lesions of the stoma and, therefore, scar keloid, narrowing of the lumen and embedding of the tube itself. In conclusion, in our personal experience, we are of the opinion that translaryngeal tracheotomy, since it is easily carried out and is a slightly invasive procedure, plays a very important role in the management of the Intensive Care Unit patient but should be reserved for the few cases requiring tracheostomy for limited periods of time, in low risk patients and within the first 18 days after the acute damaging event.

Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial fibrillation.

AIM: The spectrum of histological alterations, namely atrial amyloidosis, in the right and left atria of patients with chronic persistent atrial fibrillation (AF) and rheumatic heart disease is not completely known. METHODS AND RESULTS: One hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from 72 patients with rheumatic valve disease and chronic AF undergoing cardiac surgery for valve replacement or repair and AF treatment were histologically evaluated for the presence of amyloid deposits. One hundred and four specimens of left and right auricles from 52 patients in sinus rhythm with severe chronic heart failure undergoing heart transplant were also analyzed (controls). Amyloid was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%) controls. Amyloid was related to the presence and duration of AF, was more frequently found in left atrial samples and was independent of age. On stepwise logistic regression analysis, AF duration and female gender were independently related to amyloid deposition. CONCLUSIONS: Patients with long-standing AF and rheumatic heart disease have a very high prevalence of atrial amyloidosis. Amyloid deposition is more frequent in left than in right atrial appendage and correlates with AF duration and female gender. Amyloid deposition could constitute an additional histological feature in the structural remodeling of atria during long-standing AF, at least in rheumatic valve disease. Persistence of AF might play a pivotal role in promoting amyloid deposition.

Osteoma of maxillary sinus: case report.

Cranio-facial osteomas are frequent in the nasal and paranasal sinuses, particularly in fronto-ethmoidal sites; other sinus cavities are more rarely affected. Although various theories (embryogenetic, traumatic and inflammatory) have been advanced to explain the pathogenesis, it is difficult to establish a specific cause-effect relationship. Nasal and paranasal osteomas are generally asymptomatic and are diagnosed on the basis of X-rays performed for other conditions, the onset of sinusitis-like symptoms or the appearance of complications due to sinus diseases. These cases require surgical removal to avoid the risk of short- or long-term complications or to solve any that may already exist. Herein, a rare case of osteoma of the maxillary sinus is described and the possible aetiopathogenetic role of traumatic and inflammatory factors described. The main clinical and therapeutic data concerning this lesion are examined.

Folate supplementation after heart transplantation: effects on homocysteine plasma levels and allograft vascular disease.

BACKGROUND AND AIMS: After heart transplantation, the effects of folate supplementation on total homocysteine plasma levels (THcy) and heart allograft vascular disease (AVD) remain unclear. METHODS: Accordingly, we prospectively analyzed 48 heart transplant receipients referred for routine follow-up from July to September 1998 (age 54+/-11 years, 75% male, 35+/-27 months from transplant). Among these patients, 17 were treated with folate supplementation for 12 months (Group F), while 31 cross-matched for age, gender, serum creatinine and time from transplant (P>0.3 vs Group F for all) did not assume folate supplementation (Group NF). Routine coronary angiography for AVD detection was routinely obtained in every patient. RESULTS: THcy overall increased during the study period (from 16.6+/-6.5 to 19.4+/-7.6 micromol/l, P<0.001), and a strong trend toward higher THcy was observed in patients presenting AVD (22.4+/-8.7 vs 17.6+/-6.8 micromol/l, P=0.051). After 12 months THcy was lower in Group F as compared to Group NF (16.2+/-5.6 vs 21.1+/-8.1 micromol/l, respectively, P=0.033). CONCLUSIONS: Our results demonstrate that THcy increases over time in heart transplant recipients, and a strong trend toward higher THcy is observed in the presence of AVD. Since folate supplementation appears to positively influence THcy, a favorable effect of folate on AVD can be hypothesized.

Arrhythmogenic right ventricular cardiomyopathy: clinicopathologic correlation based on a revised definition of pathologic patterns.

Different morphologic features of arrhythmogenic right ventricular cardiomyopathy (ARVC) have been described. However, it is still unclear whether they correspond to distinct forms of the same disease. A pathologic study was performed on a series of ARVC (15 from heart transplant and 12 from autopsy) from 2 Italian referral university hospitals. Based on both myocellular features and the nature of myocardial replacement, hearts were divided into 2 groups: infiltrative, with a lacelike pattern of transmural fatty infiltration and strands of normal residual cardiomyocytes (n = 11); and cardiomyopathic, with massive myocardial replacement by fibro fatty tissue and cardiomyopathic changes (such as hypertrophy and myofibril loss) of residual cardiomyocytes (n = 16). Hearts from the infiltrative group were mostly obtained at autopsy of patients who died suddenly. Fatty substitution was limited almost exclusively to the right ventricle. Mitral valve dysplasia (prolapse or cleft) was frequently present. Hearts from the cardiomyopathic group came mainly from heart transplants for congestive heart failure. Fibro fatty replacement was more extensive, usually biventricular. Active myocarditis and features suggestive of myocardial transdifferentiation were also observed. Despite these differences in clinical outcome and morphologic features, patients from the 2 groups showed similar mean age, sex distribution, occurrence of threatening ventricular arrhythmias, and prevalence of family history of sudden death, arrhythmias, or cardiomyopathy. Infiltrative and cardiomyopathic patterns represent different clinical and pathologic subsets of ARVC. Myocellular features are an important clue in the distinction between the two entities. The differentiation between the 2 patterns is feasible on endomyocardial biopsy and could give important prognostic information.

Diagnosis and management of fetal cardiac anomalies: 10 years of experience at a single institution.

OBJECTIVE: To assess the diagnostic accuracy of fetal echocardiography and the outcome of cardiac malformations diagnosed in utero. DESIGN: A retrospective study. METHODS: The archives of our ultrasound laboratory were searched for fetal cardiac abnormalities in the period 1991-2001. RESULTS: Diagnosis of a fetal cardiac anomaly was made in 339 pregnancies at a mean gestational age of 26.2 weeks. Pathology or a detailed postnatal follow-up was available in 260 cases, and the prenatal diagnosis was accurate in 236 cases (91%). Discrepancies included nine false positive diagnoses (six ventricular septal defects and three coarctation of the aorta) and 15 cases in which a cardiac anomaly different from the one suspected in utero was documented. Of the 142 fetuses with isolated cardiac malformations (no extracardiac anomalies, normal chromosomes) that were delivered in our center, 114 were alive (80.2%) at a mean follow-up of 38 months (range, 1-120 months). In this group of patients, conotruncal anomalies and univentricular lesions were the most frequent types of anomaly, and had a survival rate of 87% and 57%, respectively. Hypoplastic left heart was the most frequent isolated congenital heart defect in infants that were delivered (19 cases) and it was associated with a survival rate of 37%. CONCLUSION: In expert hands, fetal echocardiography is highly accurate. The long-term prognosis of cardiac lesions diagnosed in utero is similar to that reported in series of infants diagnosed after birth. The only exception is hypoplastic left heart in which the survival rate is much lower than expected from postnatal studies.

Increasing plasma homocysteine during follow-up in heart transplant recipients: effects of folate and renal function.

BACKGROUND: Hyperhomocysteinemia is a common finding in heart transplant recipients and may represent a risk factor for graft failure. However, the time-course, determinants and effects of medical therapy on total homocysteine plasma levels after heart transplantation remain undetermined. The aim of this study was to prospectively analyze 1) the time-course of total homocysteine in heart transplant recipients; 2) the effects of folate supplements and cyclosporine A on total homocysteine; 3) the relation among renal function, serum vitamin levels, and total homocysteine. METHODS: Fifty-two heart transplant recipients consecutively evaluated for routine follow-up during 1998 were included in the study (mean age 54 +/- 12 years; 28% female). Among the 52 patients, 10 patients were treated with folate for the entire period of the study (Group F), while 26 patients never received folate (Group NF). The remaining 16 patients who did not take folate on a regular basis were excluded from subgroup analysis. Total homocysteine and creatinine plasma levels were assayed at entry into the study (time 0) and at the end of the study, 12 months later (time 12). RESULTS: Homocysteinemia increased significantly from time 0 to time 12 (p < 0.001), regardless of creatinine plasma levels (p = 0.03) and folate intake (p < 0.01). However, total homocysteine levels were lower in Group F compared to Group NF at time 0 and time 12 (p < 0.02). On multivariate analysis, time of follow-up, serum creatinine and lack of folate intake were positive independent predictors of total homocysteine. CONCLUSIONS: Homocysteinemia increased over time in heart transplant recipients, regardless of renal function and folate administration. Lower total homocysteine levels were associated with folate intake, suggesting that folate supplements may play a role in the prevention of vascular allograft disease.

Assessment of restrictive cardiomyopathy of amyloid or idiopathic etiology by magnetic resonance imaging.

This study was designed to assess the role of magnetic resonance imaging in the differential diagnosis of amyloid and idiopathic etiology of cardiomyopathy. This technique demonstrated the capability to differentiate the 2 forms, providing high-resolution evaluation of the myocardial wall and detecting the infiltrative pathology by tissue characterization.

Cardiac papillary fibroelastoma of the mitral valve chordae.

Papillary fibroelastomas are rare, benign, primary cardiac tumors, usually single and small. The neoplasm consists of a leafy, soft excrescence typically located on the cardiac valves. Although papillary fibroelastomas are usually an asymptomatic incidental finding at autopsy, or during cardiac operation, they are occasionally associated with embolic coronary or cerebral symptoms. A case of a patient is reported with papillary fibroelastoma of the mitral valve chordae, who presented several transitory ischemic attacks characterized by loss of conscience, visual bilateral deficit and right emiparesis. Because of their potential systemic embolization, we believe that these lesions should be always excised.

Causes of late failure after heart transplantation: a ten-year survey.

BACKGROUND: Little is known about the causes of death of heart transplant recipients who survive long-term. METHODS: The pathologic and clinical records of 97 patients who underwent heart transplantation in Italy from 1985 to 1995 and died (85 of 97) or underwent retransplantation (12 of 97) at least 2 years after transplantation were surveyed. Graft failures were classified as late (occurring between 2 and 5 years after transplantation) and belated (more than 5 years). RESULTS: Graft vasculopathy was the single most common cause of death (40.0%) and the only cause of late retransplantation. Tumors ranked second (23.5% of deaths), but the expected non-Hodgkin's lymphomas and Kaposi's sarcoma were accompanied by a high number of lung cancers (especially metastasizing adenocarcinomas). They were followed by the emergence or recurrence of pretransplantation diseases (9.4%), fatal infections (exclusively bacterial) (4.7%), the development of transmissible diseases (viral hepatitis and acquired immunodeficiency syndrome, 4.7%), and late acute rejection (2.3%). The distribution of failures differed in the late and belated periods: death and organ loss proportions for graft vasculopathy, respectively, fell and rose from the late to the belated period; some types of malignancy and fatal acute rejection were never observed in the belated period, whereas the emergence of pretransplantation diseases prevailed in the belated period. Graft vasculopathy was more frequent and tumors were less frequent among patients undergoing transplantation for ischemic heart disease. CONCLUSIONS: The reasons why heart transplant recipients die or undergo retransplantation, respectively, in the late and belated periods slightly differ from one another and are widely different than in short-term survivors.