The humoral response of mRNA COVID-19 vaccine in hematological diseases: The HEMVACO study.

OBJECTIVES: The HEMVACO study evaluated the humoral response after mRNA anti-SARS-CoV-2 vaccination in an hematological cohort. METHODS: HEMVACO was a prospective, multicentric study registered in ClinicalTrials.gov, number NCT04852796. Patients received two or three doses of BNT162b2 vaccine or mRNA-1273 vaccine. The SARS-CoV-2 TrimericS IgG titers were measured 1, 3, 6 and 12 months after the second dose. RESULTS: Only 16 patients (11.6%) were naive of hematological treatment and 77 patients (55.8%) were on active treatment for hemopathy. Among the 138 analyzed patients, positive antibody titer at 1 month was obtained in 68.1% of patients with mean serology at 850±883 BAU/ml. Risk factors for vaccine failure were anti-CD20 therapy (OR=111[14.3-873]; P<0.001), hypogammaglobulinemia under 8g/L (OR=2.49[1.05-5.92]; P=0.032) and lymphopenia under 1.5G/L (OR=2.47[1.18-5.17]; P=0.015). Anti-CD20 therapy induced no anti-SARS-CoV-2 seroconversion (96%). Seventy-eight patients (56.5%) received a third dose and could reach the SARS-CoV-2 TrimericS IgG titer of high-risk patients (P=0.54). The median titer at 379 BAU/ml distinguished two groups of vaccine response (99±121 BAU/ml versus 1,109±678 BAU/ml). CONCLUSION: Vaccination should be performed before anti-CD20 therapy if the hemopathy treatment can be delayed. Administration of the third vaccine dose was interesting for patients with suboptimal response, defined by a 379 BAU/ml titer in our study.

[Cutaneous periarteritis nodosa recurring over a period of 30 years in streptococcal infections and progressing toward systemic vasculitis]. / Périartérite noueuse cutanée récidivant depuis 30 ans lors d'infections streptococciques et évoluant vers une vascularite systémique.

INTRODUCTION: Periarteritis nodosa (PAN) is a form of vasculitis affecting the small and medium-sized arteries. Below, we report a case of cutaneous PAN relapsing in streptococcal infections over a period of 30 years and progressing towards systemic vasculitis. CASE REPORT: A 35-year-old man was hospitalised for a retro-pharyngeal access associated with fever, arthralgia, myalgia and inflammatory subcutaneous nodules. Peripheral neurological signs were also seen with deficiency of the elevator muscles in the right foot. Examination of a biopsy from a nodule showed a characteristic image of PAN. Following drainage of the abscess, a favourable outcome was obtained with antibiotics and systemic corticosteroids. History taking showed that the patient had presented similar episodes since the age of 5 years involving arthralgia, myalgia and inflammatory subcutaneous nodules. These episodes appeared to follow a streptococcal infection, of which there was either clinical suspicion or objective elevation of antistreptolysin O (ASLO) titre. Skin biopsy resulted in diagnosis of cutaneous PAN 25 years earlier. In all cases, improvement was achieved by oral corticosteroids combined with treatment of the actual infection. DISCUSSION: In addition to the classic association with hepatitis B, and occasionally hepatitis C, PAN may be associated with streptococcal infections. The cases of post-streptococcal PAN described in the literature are predominantly cutaneous, although it is not rare to find associated arthromyalgia and sensory neurological impairment. We examined three cases of cutaneous PAN with long-term follow-up described in the literature. They began in childhood and the outcome was benign, with no systemic manifestations. Our case differed in terms of the appearance of motor neurological involvement. CONCLUSION: Post-streptococcal PAN of childhood onset generally carries a better prognosis than adult systemic forms. However, our case shows that on rare occasions, there may be very long progression complicated by systemic involvement.

The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis.

We have cloned from a mouse placenta cDNA library a mouse homologue of the human stromelysin-3 (ST3) cDNA, which codes for a putative matrix metalloproteinase expressed in breast carcinomas. The ST3 protein is well conserved between humans and mice, and the pattern of ST3 gene expression is similar in both species, and shows expression in the placenta, in the uterus, and during limb bud morphogenesis. We show that the ST3 gene can also be expressed in the normal mouse mammary gland. ST3 gene expression was not detected during mammary growth, neither in virgin nor in pregnant mice, but was specifically observed during postlactating involution of the gland, an apoptotic process associated with intense extracellular matrix remodeling. ST3 transcripts were found in fibroblasts immediately surrounding degenerative ducts, suggesting that ST3 gene expression may be associated with the basement membrane dissolution, which occurs during mammary gland involution. Since the ST3 gene is also specifically expressed in fibroblastic cells surrounding invasive neoplastic cells of breast carcinomas, we suggest that ST3 is implicated in extracellular matrix remodeling processes common to mammary apoptosis and breast cancer progression.

[Voluminous nodular splenomegaly in Gaucher disease: a case report]. / Volumineuse splénomégalie nodulaire au cours d'une maladie de Gaucher: à propos d'une observation.

Patients affected by type 1 Gaucher disease (an autosomal recessive inheritance lysosome storage disorder) develop nodular splenomegaly in 20 to 30% of cases where imiglucerase therapy proves ineffective. The lack of response to imiglucerase therapy on spleen nodules could be an indication of the existence or development of a malignant spleen. We report a 47-year-old man with Gaucher disease who presented with a voluminous splenic nodule, in whom therapy was delayed. Regular monitoring of patients is the most important factor to predict and therefore prevent morbidity.

[Acquired factor XI inhibitor and chronic lymphocytic leukemia]. / Allongement du TCA chez un patient atteint de leucémie lymphoïde chronique : à propos de la très rare découverte d'un autoanticorps antifacteur XI.

Autoimmune phenomena, most frequently autoimmune hemolytic anemia, is a well-known complication of lymphoproliferative diseases. We report a very rare association of a chronic lymphocytic leukemia with an acquired factor XI inhibitor. A 87-year-old man presented with auto-immune hemolytic anemia. He had untreated chronic lymphocytic leukemia for the past three years and renal insufficiency. Before surgical procedure for arteriovenous fistula, we discovered a very prolonged activated partial thromboplastin time (APTT), and an acquired factor XI inhibitor was detected. The patient was successfully treated with immunosuppressive therapy. Among patients with lymphoproliferative disorders the discovery of a prolonged APTT implies to search for rare autoimmune phenomena like acquired coagulation factor inhibitors.

Pneumocystis carinii pneumonia in patients with hematologic malignancies: a descriptive study.

Objectives. A retrospective multicentric study was conducted over a five-year period to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating hematologic malignancies.Results. The study included 60 HIV-negative patients with 18 non-Hodgkin's malignant lymphoma (30%), 13 chronic lymphocytic leukaemia (21.7%), 10 acute leukemia (16.6%), 5 multiple myeloma (8.3%), 4 Waldenström's diseases (6.6%), 4 chronic myeloid leukemia (6.6%), 3 myelodysplasia (5%), 2 Hodgkin's diseases (3.3%) and 1 thrombopenia. Bronchoalveolar lavage was diagnostic in all patients. Forty-nine patients received cytotoxic drugs (81.7%), 25 (41.7%) a long-term corticotherapy and 15 (25%) underwent bone marrow transplantation. Twenty-seven patients (45%) required admission in the intensive care unit, 35 (58.3%) received an adjunctive corticotherapy and 18 mechanical ventilation (30%). Twenty patients (33.3%) died of PCP. A previous long-term corticotherapy (p=0.04), high respiratory (p=0.05) and pulse rates (p=0.02), elevated C reactive protein (p=0.01) and mechanical ventilation (OR=13.37; IC: 1.9-50) were associated with a poor prognosis. Adjunctive corticotherapy did not modify the prognosis.Conclusions. These results suggest that PCP can occur during the course of various hematologic malignancies, not only lymphoproliferative disorders. Prognosis remains poor. The diagnosis should be advocated more frequently and earlier to improve the prognosis.

[Localized periarteritis nodosa with periostal new bone formation]. / Périartérite noueuse localisée et atteinte osseuse.

INTRODUCTION: Polyarteritis nodosa is a disease process with a wide clinical spectrum, ranging from a severe generalized multisystem disorder to a more benign condition which may remain limited to the skin, muscles and peripheral nerves, and is termed cutaneous polyarteritis nodosa. Periosteal bone formation is uncommon in this condition. EXEGESIS: We report two cases (two female patients of 80 and 55 years of age, respectively) who complained of red, tender nodules of legs and bone pain. Histological changes were those of necrotizing arteritis of the small and medium arteries in the panniculus and dermis. Bone X-ray showed periosteal bone formation. CONCLUSION: In patients with pain, skin changes and swelling of the lower limbs, the diagnosis of periarteritis nodosa with periostitis has to be considered.

[Extrapulmonary tuberculosis in the central western region. Retrospective study of 217 cases (Gericco 1991-1993)]. / Tuberculose extrapulmonaire dans la région centre-ouest. Etude rétrospective de 217 cas (Gericco 1991-1993).

OBJECTIVES: To analyze the epidemiological, clinical and diagnostic characteristics of extrapulmonary tuberculosis in western France observed from 1991 to 1993 in different patients populations (HIV+ infected patients, immunosuppressed non-HIV infected patients, non-immunosuppressed patients) and according to various localizations (lymph nodes, bone and joints, genital organs, nervous system and meninges, miliary disease). METHODS: This retrospective study included 217 cases of extrapulmonary tuberculosis diagnosed from 1991 to 1993 in western France by GERICCO (Groupe d'Epidémiologie et de Recherche en Infectiologie Clinique du Centre-Ouest). Demographic, clinical, biological, microbiological and radiographic characteristics as well as clinical course on specific therapy were assessed. RESULTS: Extrapulmonary tuberculosis generally occurred most often in immunosuppressed patients but 34% of cases were observed in people without any underlying disease or risk factors. Delay to diagnosis was especially long in the non-immunosuppressed patients (mean = 96 days) but shorter in the HIV-infected patients (mean = 59 days). It was shorter in case of nervous system involvement (mean = 52 days) or military disease (mean = 80 days) than in bone and joints (mean = 120 days) and lymph nodes (mean = 102 days). Microbiologically proven tuberculosis represented only 75% of cases despite numerous investigations. Overall prognosis was good except in nervous system and meninges localizations. Failures were mainly due to death in immunosuppressed patients. CONCLUSION: Extrapulmonary tuberculosis remains frequent even in patients lacking risk factors. In 50% of cases, confirmation of diagnosis takes more than one month. In case of doubt, clinicians should not wait for laboratory results before implementing empirical specific therapy.

[Epidemiology of candidemia: a one-year prospective observational study in the west of France]. / Epidémiologie des candidémies: étude observationnelle prospective d'un an dans l'Ouest de la France.

OBJECTIVE: A one-year prospective, observational study was conducted in the west of France, to evaluate the epidemiology of candidemia. METHOD: During the year 2004, each patient with at least one blood culture yielding Candida sp. was included. For each episode of candidemia, mycological, demographical, clinical, and therapeutic data, as well as outcome, were collected. RESULTS: One hundred and ninety-three strains of Candida sp. were isolated in 186 patients, Candida albicans accounting for 54.9%, Candida glabrata for 18.7%, Candida parapsilosis for 12.9%, Candida tropicalis for 4.7% and Candida krusei for 4.1% of these isolates. A percentage of 84% of the Candida isolates were fully susceptible to fluconazole in vitro. Dose-dependent susceptibility or resistance to fluconazole was detected in more than one third of the Candida glabrata strains, of which 36% were also resistant to voriconazole. Two-thirds of the patients were males, and the mean age was 61.5 years. A percentage of 37% of patients were hospitalized in intensive care units. The main predisposing factors for candidemia were broad-spectrum antibiotics (75.8%), central venous catheter (72.6%), cancer or hematologic malignancy (47.3%), recent surgery (42.5%), total parenteral nutrition (37.6%). One hundred and fifty-four patients were treated with antifungal therapy, two-thirds of whom received fluconazole as first-line agent. Mortality was 49% overall, and was significantly higher in case of septic shock, advanced age, and absence of catheter removal.

[Lymphoma involving the temporal artery]. / Localisation temporale d'un lymphome.

Involvement of the temporal arteries, considered to be the hallmark of giant cell arteritis, is rather rare in other pathologic processes. We describe a patient with lymphoma involving temporal artery. A 68-year-old man has been followed closely without therapy since 1989 for a low-grade non-Hodgkin lymphoma. He presented in 1995 with asymptomatic nodules on the temporal artery with preservation of the pulse. Temporal artery biopsy showed periarterial infiltration of mononuclear cells in keeping with follicular mixed cell lymphoma. The differential diagnosis of temporal arteritis must therefore, include other vasculitides, light chain amyloidosis but also lymphoma and emphasize the need for a temporal artery biopsy.

Cell-free Fc-gamma receptor III in sera from patients with systemic lupus erythematosus: correlation with clinical and biological features.

Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA based upon a sandwich of two monoclonal antibodies. The standard curve was obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25 microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be lower in 11 patients with renal involvement than in those without. For the biological parameters, we observed that the 27 patients who presented lymphopenia also had a lower level of cell-free Fc gamma RIII when compared to the 23 patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by presumably activated polymorphonuclear cells.

A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas.

A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies.

[Multifocal tuberculosis. Apropos of 49 cases in the midwest region. GERICCO (Group for Epidemiology and Research in Clinical Infections of the Central West of France), 1991-1993]. / Tuberculose multifocale. A propos de 49 cas dans la région Centre-Ouest (Géricco, 1991-1993).

Diffuse or multifocal tuberculosis (TB) accounts for 9% to 10% of cases of extrapulmonary TB and carries a poor prognosis with a mortality rate of 16% to 25%. Forty-nine cases of multifocal TB defined as involvement of two extrapulmonary sites with or without pulmonary TB were reviewed. Mean patient age (+/- SD) was 50 +/- 18 years. Twenty-three per cent of patients were immigrants. A history of TB and contact with a TB patient were found in 23% and 18% of cases, respectively. Of the 52% of immunocompromised patients, 38% were HIV-positive. The skin tuberculin test was positive in 67% of cases. Mean time from symptom onset to admission was 80 +/- 77 days (median, 58 days). The 49 patients had a total of 128 TB foci. Six patients had positive blood cultures. The tubercle bacillus was recovered from the extrapulmonary sites in 88% of cases. Mean treatment duration was nine months. Recovery from the TB was achieved in 64% of cases. The overall mortality rate was 47%, and 33% of patients died as the direct result of TB. Most deaths occurred in immunocompromised patients. A high index of suspicion for multifocal TB should be maintained in immunocompromised patients, even those who test negative for the HIV.