Peg-IFNα/ribavirin/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis: results at week 24.

BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

2022 SPILF - Clinical Practice guidelines for the diagnosis and treatment of disco-vertebral infection in adults.

These guidelines are an update of those made in 2007 at the request of the French Society of Infectious Diseases (SPILF, Société de Pathologie Infectieuse de Langue Française). They are intended for use by all healthcare professionals caring for patients with disco-vertebral infection (DVI) on spine, whether native or instrumented. They include evidence and opinion-based recommendations for the diagnosis and management of patients with DVI. ESR, PCT and scintigraphy, antibiotic therapy without microorganism identification (except for emergency situations), therapy longer than 6 weeks if the DVI is not complicated, contraindication for spinal osteosynthesis in a septic context, and prolonged dorsal decubitus are no longer to be done in DVI management. MRI study must include exploration of the entire spine with at least 2 orthogonal planes for the affected level(s). Several disco-vertebral samples must be performed if blood cultures are negative. Short, adapted treatment and directly oral antibiotherapy or early switch from intravenous to oral antibiotherapy are recommended. Consultation of a spine specialist should be requested to evaluate spinal stability. Early lifting of patients is recommended.

Autoimmune bullous skin diseases occurring under anti-tumor necrosis factor therapy: two case reports.

BACKGROUND: Anti-tumor necrosis factor (TNF) agents are increasingly being used for a rapidly expanding number of rheumatic and systemic diseases. As a result of this use, and of the longer follow-up periods of treatment, there are a growing number of reports of the development of autoimmune processes related to anti-TNF agents. The use of anti-TNF agents has been associated with more and more cases of autoimmune diseases, principally cutaneous vasculitis, lupus-like syndrome, systemic lupus erythematosus and interstitial lung disease. OBSERVATIONS: We report 2 cases of autoimmune bullous skin disease occurring in patients undergoing TNF-targeted therapy: a bullous pemphigoid and a pemphigus foliaceus. Both patients were treated by anti-TNF agents for rheumatoid arthritis and showed improvement following interruption of that treatment. Here, we discuss the relationship between anti-TNF therapy and the occurrence of autoimmune bullous disease. CONCLUSION: Anti-TNF agents should be considered as a potential cause of drug-induced autoimmune bullous skin disease.

[Haematological complications of prostatic cancer: 2 cases, one revealing the neoplasia]. / Complications hématologiques du cancer de prostate: à propos de deux cas dont un révélateur.

INTRODUCTION: We report two cases of patients with prostate cancer who underwent haematological complications from the disease. CLINICAL CASES: Diffuse intravascular coagulopathy (with thrombopenia) was observed in two patients (55 and 59 years-old) diagnosed with prostate cancer. In one patient who had normal prostate at clinical examination, thrombopenia with incomplete diffuse intravascular coagulopathy and biological inflammatory led to diagnosis. It was initially controlled by hormonal therapy and secondary by chemotherapy. In the other patient diffuse intravascular coagulopathy followed introduction of hormonal therapy and lead to the patient's death. DISCUSSION: Patients with metastatic hormone-refractory prostate carcinoma may have life-threatening coagulation complications due to their disease. Diffuse intravascular coagulopathy is the most frequent coagulation complication. Other coagulopathies associated with prostate cancer are thrombocytopenic thrombotic purpura, thrombosis, Trousseau's syndrome and acquired factor VIII inhibitor development. Usually these haematological manifestations complicate the course of the disease and appear to have a bad prognosis. But thrombopenia or haematologic features may lead to the diagnosis of medullary metastatic prostatic cancer, even if the prostate appears normal at the initial clinical examination.

[Tumor-induced osteomalacia caused by a late-revealing phosphaturic mesenchymal tumor]. / Ostéomalacie secondaire à une tumeur mésenchymateuse phosphaturique de révélation tardive.

INTRODUCTION: Osteomalacia is associated with diffuse pain and multiple fractures and therefore, diagnosis and treatment of this condition are necessary. Clinicians should be aware of an uncommon mechanism of osteomalacia where hypophosphataemia is secondary to renal phosphaturia because of the production by a mesenchymal phosphaturic tumor of FGF-23. This tumor should be localized and removed to cure this tumor-induced osteomalacia. OBSERVATION: A 70-year-old female patient was admitted to explore diffuse pain caused by multiple fractures secondary to osteomalacia. Despite vitamin D supplementation, she remained profoundly hypophosphoremic with major renal phosphaturia. A tumor-induced mechanism was suspected because of high level of FGF-23. It took more than three years of investigation to spot the causal phosphaturic mesenchymal tumor despite annual repetition of indium-labelled scintigraphy and PET-scan. The resection of the tumor, located between two phalanges of the right foot, cured the patient with sustained normal rate of serum level of phosphorus after two years. CONCLUSION: Tumor-induced osteomalacia is a diagnostic challenge because the localization of the tumor may be a long process. Patients should be monitored clinically and imaging studies repeated until a diagnosis is made and the causal tumor removed.

[Combined heart and kidney transplantation in Fabry's disease: Long-term outcomes in two patients]. / Transplantation combinée cœur­rein au cours de la maladie de Fabry : suivi à long terme de deux patients.

INTRODUCTION: Fabry disease is a lysosomal storage disorder linked to an alpha-galactosidase A deficiency that can lead to heart and kidney failure. There is little data about the prognosis of patients who undergo a combined heart and kidney transplantation. CASE REPORTS: Two brothers who were diagnosed with Fabry disease after the age of 30 years underwent a combined heart and kidney transplantation at respectively 49 and 42 years of age because of a severe hypertrophic cardiomyopathy with end stage renal failure. They are alive respectively 4 and 9 years after the transplantation. No recurrence of the disease in the transplanted organs has been found. CONCLUSION: Combined heart and kidney transplantation in Fabry disease is an efficient therapy for the cardiomyopathy and kidney failure. Its prognosis can be good when the patients are carefully selected. However, an early diagnosis is critical in order to avoid a procedure associated with a high perioperative mortality.

[Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A retrospective multicentric study of 28 adult cases]. / Déficit en sphingomyélinase acide (maladie de Niemann-Pick B) : une étude rétrospective multicentrique de 28 patients adultes.

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive disease with a clinical spectrum ranging from a neurovisceral infantile form (Niemann-Pick disease type A) to a chronic visceral form also encountered in adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric analysis of French adult patients with ASMD over the period 1985-March 2015. Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight patients (19 males, 9 females) were analyzed. Diagnosis was made before the age of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement and interstitial lung disease. Biological abnormalities included: thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL) cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of unknown significance (n=5), normal prothrombin level discordant with low factor V (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing was performed in 25 cases. The frequent p.R610del mutation was largely predominant, constituting 62% of the non-related alleles. During the follow-up period, three patients died before 50 years of age from cirrhosis, heart failure and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B) associates spleen/liver enlargement and interstitial lung disease. Early diagnosis and appropriate management are essential for reducing the risk of complications, improving quality of life, and avoiding inappropriate procedures such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3 therapeutic trial with IV infusion of recombinant enzyme is on-going.

[Knee septic arthritis]. / L'arthrite septique du genou.

The development of antibiotics and arthroscopic treatment have been two major turning points in the management of septic arthritis of the knee joint. We report a retrospective review of 78 patients managed in three surgery units and one rheumatology unit. Management practices varied between the units. Joint aspiration was proposed for all patients seen by rheumatologists. Certain surgeons proposed arthroscopy systematically at admission while others preferred a more selective approach. Arthroscopic wash-out was proposed as the first-line procedure for only 33 patients. All were given systemic antibiotics using a variety of protocols. The course under antibiotic treatment confirmed the potential gravity of septic arthritis of the knee joint since two patients died and 34 required surgery, half of which had more than one operation. The functional outcome at mean 19 months was rather poor. Only 65 knees were free of any implant and only 40 (62%) were pain free. Mean flexion was 116 degrees and 11 patients (17%) had significant flexion contracture. Factors of poor prognosis were initially high sedimentation rate, advanced stage according to Gächter, presence of specific germs (meti-R S. aureus, Gram-negative bacilli), and failure of first-line treatment. A management algorithm was proposed: initial aspiration for evacuation, medical treatment alone if there is no synovitis, and reduction synovectomy otherwise. The key to success is early well adapted treatment.

[Acid sphingomyelinase deficiency and spleen trauma: splenectomy or not splenectomy?]. / Déficit en sphingomyélinase acide et rupture splénique : splénectomie ou traitement conservateur ?

INTRODUCTION: Acid sphingomyelinase deficiency leads to a severe infantile disease (Niemann-Pick disease type A) or an attenuated form of the disease encountered in adults (Niemann-Pick type B), including pulmonary fibrosis and splenomegaly. CASE REPORT: A 52-year-old man with Niemann-Pick disease type B was admitted with splenic rupture. Embolization of the splenic artery was initially performed. Three months later, the splenic volume had increased and functional asplenia was diagnosed. Splenic scintigraphy showed 20% of functional splenic tissue. Splenectomy was finally performed because of complete necrosis of the spleen. CONCLUSION: Despite its theoretical contra-indication in Niemann-Pick disease due to a risk of respiratory insufficiency, splenectomy must sometimes be considered.

Neurosarcoidosis: signs, course and treatment in 35 confirmed cases.

Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted.

Leiomyosarcoma of the inferior vena cava. Experience with 7 patients and literature review.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumor originating in the smooth muscle of the media. Although rare, it is the most common malignancy in the IVC. One hundred and six cases have been reported thus far in the world literature, usually as isolated case reports. Clinical, radiologic, and therapeutic management and follow-up, including 7 additional cases, have been reviewed and summarized. Clinical manifestations are dependent upon the location of the tumor. The main symptom was a palpable mass for a tumor in segment I, abdominal pain for segment II, the presence of Budd-Chiari syndrome for segment III. Segment II was the most frequent site of leiomyosarcoma of the IVC, alone (n = 41) or with other segments (n = 39). Before laparotomy, clinical recognition was difficult or impossible. Recently, however, newer imaging modalities including ultrasound and CT scan have permitted earlier diagnosis. Metastases, when diagnosed, were either present at diagnosis (n = 20) or appeared as the disease progressed (n = 18). Metastatic disease frequently involved the liver, lung, lymph nodes, or bone. The small number of patients alive without metastases (16/113) must be analyzed all the more carefully because these patients were followed for less than 2 years. When prolonged follow-up is possible, the number of patients alive without neoplastic disease is significantly reduced. We found the prognosis of patients with LMS of the IVC to be poor. Diagnosis was made at autopsy for 27 patients. Among the 86 patients with follow-up information, 59 died within a mean of 16 months, and 26 were alive 25 months after the diagnosis. The main prognostic factor is topography, particularly the highest level of extension of the tumor. The upper-segment tumors have the poorest prognosis. The best therapeutic management is difficult to recommend because most of the cases in the literature did not include a sufficient follow-up. Given the very small number of patients completely free of neoplastic disease after sufficient follow-up, it seems unlikely that leiomyosarcoma of the IVC can now be cured. Patients who received a combination of surgery, radiotherapy and chemotherapy remained free of disease for longer periods. The unanswered question is: what is the best timing for each of these treatments? We recommend diagnosis of leiomyosarcoma of the IVC through biopsy guided by ultrasonography or computed tomographic scan. Therapeutic management should include large doses of chemotherapy preoperatively with or without radiotherapy to reduce tumor size.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal tuberculosis in adults. A study of 103 cases in a developed country, 1980-1994.

Spinal tuberculosis (TB) accounts for about 2% of all cases of TB. New methods of diagnosis such as magnetic resonance imaging (MRI) or percutaneous needle biopsy have emerged. Two distinct patterns of spinal TB can be identified, the classic form, called spondylodiscitis (SPD) in this article, and an increasingly common atypical form characterized by spondylitis without disk involvement (SPwD). We conducted a retrospective study of patients with spinal TB managed in the area of Paris, France, between 1980 and 1994 with the goal of defining the characteristics of spinal TB and comparing SPD to SPwD. The 103 consecutive patients included in our study had TB confirmed by bacteriologic and/or histologic studies of specimens from spinal or paraspinal lesions (93 patients) or from extraspinal skeletal lesions (10 patients). Sixty-eight percent of patients were foreign-born subjects from developing countries. None of our patients was HIV-positive. SPD accounted for 48% of cases and SPwD for 52%. Patients with SPwD were younger and more likely to be foreign-born and to have multiple skeletal TB lesions. Neurologic manifestations were observed in 50% of patients, with no differences between the SPD and SPwD groups. Of the 44 patients investigated by MRI, 6 had normal plain radiographs; MRI was consistently positive and demonstrated epidural involvement in 77% of cases. Bacteriologic and histologic yields were similar for surgical biopsy (n = 16) and for percutaneous needle aspiration and/or biopsy (n = 77). Cultures for Mycobacterium tuberculosis were positive in 83% of patients, and no strains were resistant to rifampin. Median duration of antituberculous chemotherapy was 14 months. Surgical treatment was performed in 24% of patients. There were 2 TB-related deaths. Our data suggest that SPwD may now be the most common pattern of spinal TB in foreign-born subjects in industrialized countries. The reasons for this remain to be elucidated.

Efficacy of intravenous gammaglobulin therapy in chronic refractory polymyositis and dermatomyositis: an open study with 20 adult patients.

PURPOSE: Polymyositis and dermatomyositis are inflammatory muscular diseases of unknown cause. Many interventions are available to treat patients with these conditions including corticosteroids, immunosuppressive drugs, plasmapheresis, and total body irradiation. However, these therapies are not always effective, and they may be associated with certain serious side effects. An attempt was made to evaluate the efficacy of polyvalent intravenous immunoglobulin (IVIG) in patients with polymyositis or dermatomyositis refractory to traditional treatment. PATIENTS AND METHODS: Twenty patients (16 women and 4 men; mean age 43 [16 SD] years), 14 with chronic refractory polymyositis and six with dermatomyositis, received high doses of IVIG because of the failure of traditional treatments (prednisone [19], methotrexate [10], azathioprine [6], cyclophosphamide [3], cyclosporine [3], chlorambucil [1], plasmapheresis [8], lymphopheresis [1], and total body irradiation [1]). In one patient with positive results on picornavirus serologic testing, IVIG was the first treatment choice. IVIG therapy was given with prednisone in 15 patients, with methotrexate in six patients, and with plasmapheresis in one patient. There were no changes in treatment in the 2 months before the introduction of IVIG therapy and no increases in dose during this treatment. Preparations of polyvalent human intravenous gammaglobulins with increased intact immunoglobulin G were used. Thirteen patients received 1 g/kg daily for 2 days each month, and seven patients received 0.4 g/kg daily for 5 days each month. The mean duration of treatment was 4 months. RESULTS: Clinical assessment, which consisted of the measurement of proximal muscle power, and biochemical studies were carried out before each treatment period. Significant clinical improvement was noted in 15 of the 20 patients. Mean muscle power estimated for the 20 patients before and after IVIG therapy was statistically significantly reduced (p less than 0.01). Eighteen patients showed biochemical improvement, and two patients with normal initial serum creatine kinase levels showed clinical improvement. Mean creatine kinase levels for the 20 patients during IVIG therapy showed a statistically significant decrease from the first IVIG perfusions (p less than 0.01). Side effects of IVIG therapy were noted in four patients; however, these effects were mild. During IVIG therapy, steroid doses were significantly reduced from the second or the third IVIG infusion (p less than 0.05). CONCLUSION: IVIG is an efficacious new therapy for polymyositis and dermatomyositis and should play a role in the treatment of these diseases, replacing or reducing steroid and immunosuppressive medications.

Magnetic resonance appearance of monoclonal gammopathies of unknown significance and multiple myeloma. The GRI Study Group.

STUDY DESIGN: A prospective multicenter study. OBJECTIVES: To evaluate the use of magnetic resonance imaging, in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. SUMMARY OF BACKGROUND DATA: Although multiple myeloma has been studied extensively with magnetic resonance imaging, to the authors' knowledge, no study has evaluated the clinical interest of magnetic resonance imaging in the differentiation between monoclonal gammopathies of unknown significance and multiple myeloma. METHODS: The magnetic resonance examinations of the thoracolumbar spine in 24 patients with newly diagnosed monoclonal gammopathies of unknown significance were compared with those performed in 44 patients with newly diagnosed nontreated multiple myeloma. RESULTS: All findings on magnetic resonance examination performed in patients with monoclonal gammopathies of unknown significance were normal, whereas findings on 38 (86%) of the 44 magnetic resonance examinations performed in patients with multiple myeloma were abnormal. CONCLUSION: Magnetic resonance imaging can be considered as an additional diagnostic tool in differentiating between monoclonal gammopathies of unknown significance and multiple myeloma, which may be helpful when routine criteria are not sufficient. An abnormal finding on magnetic resonance examination in a patient with monoclonal gammopathies of unknown significance should suggest the diagnosis of multiple myeloma after other causes of marrow signal abnormalities are excluded. Magnetic resonance imaging also may be proposed in the long-term follow-up of monoclonal gammopathies of unknown significance when a new biologic or clinical event suggests the diagnosis of malignant monoclonal gammopathy.

Four cases of tendinopathy in patients on statin therapy.

During the last decade, statins have been widely prescribed as lipid-lowering drugs. Their overall safety profile is good. The main musculoskeletal side effects have consisted of muscle pain and weakness, peripheral neuropathy, and a few cases of drug-induced lupus. We report the first four cases of tendinopathy in patients receiving statin therapy. There were three men and one woman. The diagnoses were extensortenosynovitis at the hands (case 1), tenosynovitis of the tibialis anterior tendon (case 2), and Achilles tendinopathy (cases 3 and 4). Two patients were on simvastatin and two on atorvastatin. The tendinopathy developed 1 to 2 months after treatment initiation. The outcome was consistently favorable within 1 to 2 months after discontinuation of the drug. Similar cases have been reported to French pharmacovigilance centers. This report of four cases of tendinopathy draws attention to a possible and heretofore unrecognized side effect of a drug class that is becoming increasingly popular. Statins are effective in lowering high cholesterol levels in patients with type IIa or IIb hypercholesterolemia. They have been widely used for the last decade, particularly in the secondary and primary prevention of major coronary events. Statins act by inhibiting the enzyme hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. Although most patients tolerate statins extremely well, a few experience side effects requiring treatment discontinuation. Reported musculoskeletal side effects include myalgia and a few cases of rhabdomyolysis and polymyositis. Induced lupus and peripheral neuropathy are exceedingly rare.

[Detachment of valve prostheses. Apropos of 24 cases]. / Désinsertions de prothèses valvulaires. A propos de 24 cas.

A series of 24 cases of paraprosthetic valvular regurgitation, 10 mitral and 14 aortic, in 19 out of a group of 634 operated patients with a total of 822 prosthetic heart valves is reported. The presenting features are dominated by auscultatory changes, though inconstant episodes of heart failure, and, in aortic prostheses, the high incidence of infective endocarditis. Paraclinical investigations are of variable value; cineradiography in aortic valves and phonocardiography in mitral valves are useful; catheterisation with ventriculography or aortic angiography according to the case under study are the investigations of choice, especially in mitral regurgitation where it is essential. Typical clinical settings for these problems are valve ring dilatation calcification, and previous or active infective endocarditis. The indications for urgent surgery depend on the clinical signs, the presence of heart failure, haemolysis, active endocarditis and deterioration despite medical treatment. The series compares the data in mitral paraprosthetic regurgitation, difficult to diagnose but with a reasonably good prognosis, and aortic paraprosthetic regurgitation, easier to diagnose but associated with a poor prognosis due to the high incidence of associated endocarditis.

[Postoperative combined medullary sclerosis revealing Biermer's disease: toxic effect of nitrous oxide]. / Sclérose combinée de la moelle post-opératoire révélant une maladie de Biermer: toxicité du protoxyde d'azote.

Combined medullary sclerosis developed suddenly postoperatively in a patient with unknown Biermer's disease. The neurological lesions were undoubtedly induced by nitrogen protoxide via an inactivation of vitamin B12.

[The advantages of histological samples in sarcoidosis. Retrospective multicenter analysis of 618 biopsies performed on 416 patients]. / Rentabilité des prélèvements histologiques au cours de la sarcoïdose. Analyse rétrospective multicentrique de 618 biopsies pratiquées chez 416 malades.

The diagnosis of sarcoidosis is based on the finding of an epithelioid granuloma at histological examination. A retrospective study of 618 biopsies obtained from 416 patients with sarcoid disease showed an average sensitivity of 69 p. 100. The sensitivity of guided biopsies, especially skin and lymph node biopsies, was almost 90 p. 100, whereas that of blind biopsies tended to increase with the degree of hazard involved, ranging from 49 p. 100 in proximal bronchial biopsy to 70 p. 100 in liver needle biopsy. When treatment is not urgently required, the Kveim test is safe, cheap and fairly sensitive (65 p. 100 positive results).

[Bacterial endocarditis on prosthetic valves]. / Endocardites infectieuses sur prothèses valvulaires.

Bacterial endocarditis is a rare, but often lethal, complication of cardiac valve replacement. The endocarditis is called "early" when it occurs within 2 months of the operation, and "late" when it develops after that period. Contamination of the prosthesis with bacteria may occur intra-operatively or post-operatively. The clinical diagnosis is often difficult in early endocarditis when another focus of infection is present and in late endocarditis in the absence of fever and positive blood cultures. Isolation of the pathogen from blood cultures is essential to the diagnosis and treatment. Therapeutic surgery now has wider indications than formerly. The incidence of this dangerous complication can only be reduced by well-planned and well executed prophylactic measures.