Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma.

Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)-based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/µL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis.

BACKGROUND: Herpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients. OBJECTIVES: To study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adults with haematological malignancy undergoing allo-HCT. INTERVENTIONS: Antiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent. METHODS: Random-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I2). The certainty of the evidence was appraised by GRADE. RESULTS: We included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7-0.99; 15 trials, I2 = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34-0.85; n = 15, I2 = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2-0.43; n = 13, I2 = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/- pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6-1.02; n = 8, I2 = 0%), CMV disease (RR 0.47, 95% CI 0.23-0.97; n = 9, I2 = 30%) and HSV disease (RR 0.41, 95% CI 0.24-0.67; n = 4, I2 = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events. CONCLUSIONS: Antiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.

Compressive three-dimensional super-resolution microscopy with speckle-saturated fluorescence excitation.

Nonlinear structured illumination microscopy (nSIM) is an effective approach for super-resolution wide-field fluorescence microscopy with a theoretically unlimited resolution. In nSIM, carefully designed, highly-contrasted illumination patterns are combined with the saturation of an optical transition to enable sub-diffraction imaging. While the technique proved useful for two-dimensional imaging, extending it to three-dimensions is challenging due to the fading of organic fluorophores under intense cycling conditions. Here, we present a compressed sensing approach that allows 3D sub-diffraction nSIM of cultured cells by saturating fluorescence excitation. Exploiting the natural orthogonality of speckles at different axial planes, 3D probing of the sample is achieved by a single two-dimensional scan. Fluorescence contrast under saturated excitation is ensured by the inherent high density of intensity minima associated with optical vortices in polarized speckle patterns. Compressed speckle microscopy is thus a simple approach that enables 3D super-resolved nSIM imaging with potentially considerably reduced acquisition time and photobleaching.

Mature teratoma, a rare cause of virilization in adolescence.

Virilization in an adolescent patient can occur for multiple reasons (ovarian, suprarenal or exogenous reasons). We describe a 14-year-old patient with 1-year secondary amenorrhea, who had an ovarian mature teratoma as a cause of her clinical history.

Evaluation of the current National Committee for Clinical Laboratory Standards guidelines for screening and confirming extended-spectrum beta-lactamase production in isolates of Escherichia coli and Klebsiella species from bacteremic patients.

The National Committee for Clinical Laboratory Standards (NCCLS) recommendations for screening and confirming the production of extended-spectrum beta-lactamases (ESBLs) were evaluated in 115 isolates of Escherichia coli and 157 isolates of Klebsiella spp. from Israeli patients with bacteremia. All isolates were screened using cefotaxime, ceftazidime, and cefpodoxime discs. Confirmatory tests using pairs of discs containing ceftazidime, cefotaxime, or cefpodoxime in which clavulanic acid was added to one of the discs in each pair [inhibitor-potentiated disc diffusion test (IPDDT)] and two double-sided E test strips containing ceftazidime or cefotaxime with and without clavulanic acid were performed on all isolates regardless of the results of screening tests. Isolates that tested positive by one or more confirmatory tests were considered ESBL producers. Overall, 69 (25.4%) strains were found to be ESBL producers. The sensitivity of the NCCLS screening criteria ranged between 98.6% for cefotaxime and 92.8% for ceftazidime, and the specificity ranged between 100% for cefotaxime and cefpodoxime and 99.0% for ceftazidime. The sensitivity of the confirmatory tests ranged between 97.1% for the cefotaxime E test and only 75.4% for the ceftazidime IPDDT discs. All 64 isolates that fell in the intermediate and resistant categories for cefotaxime, as well as all 41 in the same categories for ceftazidime and 68 of 69 in these categories for cefpodoxime, were confirmed as ESBL producers. The use of multiple antimicrobial discs for screening isolates and combinations of IPPDT discs is needed to improve the sensitivity of confirmatory testing. It is recommended that isolates falling in the intermediate and resistant categories in disc diffusion testing be reported as ESBL producers. The use of confirmatory tests should be limited to organisms with inhibition zone diameters ranging between the NCCLS recommendations for ESBL screening and the intermediate category breakpoints.

In vitro activity of novel fluoroquinolones against Streptococcus pneumoniae isolated from children with acute otitis media.

BACKGROUND: In recent years, novel fluoroquinolones with improved activity against gram-positive organisms have been introduced into clinical practice. These drugs may be of potential benefit for the treatment of pneumococcal otitis media, including infections caused by organisms resistant to conventional drugs. METHODS: In vitro activity of 6 fluoroquinolones against 77 pneumococcal isolates from middle-ear fluid was determined by the E test. RESULTS: Resistance to penicillin, co-trimoxazole, erythromycin, clindamycin, and tetracycline was present in 59 (76.6%), 47 (61.0%), 19 (24.7%), 11 (14.3%), and 17 (22.1%) isolates, respectively. Fluoroquinolone MIC(50) and MIC(90) (in microg/ml) were as follows: ciprofloxacin: 1.0 and 3.0, levofloxacin: 0.75 and 1.0, sparfloxacin: 0.25 and 0.38, grepafloxacin: 0.25 and 0.38, trovafloxacin: 0.094 and 0.125, and moxifloxacin: 0.19 and 0.25, respectively. CONCLUSIONS: Novel fluoroquinolones and especially trovafloxacin and moxifloxacin appear to be of potential value for the treatment of acute otitis media caused by pneumococci resistant to traditional antibiotics.

Antibiotic susceptibility of Kingella kingae isolates from respiratory carriers and patients with invasive infections.

The antimicrobial drug susceptibilities of 145 isolates of Kingella kingae to eight antibiotics were determined by the disc diffusion method. In addition, penicillin MICs were determined by the Etest. Study isolates included 37 from blood, 34 from the skeletal system and 74 from respiratory carriers. All isolates were beta-lactamase negative and susceptible to erythromycin, gentamicin, chloramphenicol, tetracycline and ciprofloxacin. A single isolate exhibited resistance to trimethoprim-sulphamethoxazole, and 56 (38.6%) were resistant to clindamycin. The penicillin MIC(50) was 0.023 mg/L and the MIC(90) was 0.047 mg/L. The distribution of MIC values did not differ according to the site of isolation.

Tailored chemosensors for chloroaromatic acids using molecular imprinted TiO2 thin films on ion-sensitive field-effect transistors.

The SiO2 gate of an ion-sensitive field-effect transistor, (ISFET), is functionalized with a TiO2 film that includes imprinted molecular sites for 4-chlorophenoxy acetic acid, (1), or 2,4-dichlorophenoxy acetic acid, (2). The functionalized devices that include the imprinted interfaces reveal an impressive selectivity in the sensing of the imprinted substrates Na+ -1 or Na+ -2. The detection limit for Na+ -1 is (5+/-2) x 10(-4) M, which corresponds to 38 mV x dec(-1) in the concentration range of 0.5 to 6 mM. The detection limit for the analysis of Na+ -2 is (1.0+/-0.2) x 10(-5) M, which corresponds to 28 mV dec(-1) in the concentration range 0.1-9.0 mM. The equilibration time of the devices is ca. 5 min.

Immunization against Alzheimer's beta -amyloid plaques via EFRH phage administration.

The epitope EFRH, corresponding to amino acids 3-6 within the human beta-amyloid peptide (AbetaP), acts as a regulatory site controlling both the formation and disaggregation process of the beta-amyloid fibrils (Abeta). Locking of this epitope by highly specific antibodies affects the dynamics of the entire AbetaP molecule, preventing self-aggregation as well as enabling resolubilization of already formed aggregates. Production of such antibodies by repeated injections of toxic human Abeta fibrils into transgenic mice suggests the feasibility of vaccination against Alzheimer's disease. Here, we report the development of an immunization procedure for the production of effective anti-aggregating beta-amyloid antibodies based on filamentous phages displaying the EFRH peptide as specific and nontoxic antigen. Effective autoimmune antibodies were obtained by EFRH phage administration in guinea pigs, which exhibit AbetaP identical to the human AbetaP region. Moreover, because of the high antigenicity of the phage, no adjuvant is required to obtain high affinity anti-aggregating IgG antibodies after a short immunization period of 3 weeks. Availability of such antibodies opens up possibilities for the development of an efficient and long-lasting vaccination for the prevention and treatment of Alzheimer's disease.

Adenosine, AMP, and protein phosphatase activity in sandfly saliva.

As they probe the skin for blood, sand flies inject saliva that prevents hemostasis. Sand fly saliva also promotes leishmaniasis by suppressing immunologic functions of macrophages. Saliva of Phlebotomus papatasi, the vector of Old World cutaneous leishmaniasis, contains adenosine and AMP. We show that Ph. papatasi saliva as well as pure adenosine down-regulate the expression of the inducible nitric oxide (NO) synthase gene in activated macrophages. In addition Ph. papatasi, but not Lutzomyia longipalpis, saliva inhibits the production of NO. Taken together, these data suggest that salivary adenosine is responsible for the down-regulation of NO synthesis. Saliva of both genera Phlebotomus and Lutzomyia contains significant levels of endogenous protein phosphatase-1/2A-like activity that is heat labile, inhibitable by okadaic acid and calyculine a, and does not require divalent cations.

Serum inhibin B concentration in a prepubertal boy with gynecomastia and Peutz-Jeghers syndrome.

Gynecomastia in boys with Peutz-Jeghers syndrome and Sertoli cell tumors of gonadal origin results from increased estrogen production due to increased aromatase activity within the testicular tumor. We present a prepubertal boy with Peutz-Jeghers syndrome, gynecomastia and bilateral neoplastic Sertoli cell proliferation in whom the only abnormal hormonal profile was increased concentration of inhibin B and Pro-alpha C in serum.

[Fournier's gangrene. Our clinical experience, etiopathogenesis and management]. / Gangrena de Fournier. Nuestra experiencia clínica, etiopatogenia y tratamiento.

We report 12 cases of Fournier's Gangrene treated over an 19-month period; at Division Urology of the Hospital Gral. de Agudos Dr. José M. Ramos Mejia. We emphatized 58.3% of the patients had an urology origin. We considered diagnostic and therapeutic issues, and bibliografic review.

Anti-HIV indeterminate western blot in dialysis patients: a long-term follow-up.

In a group of 520 patients undergoing chronic hemodialysis, 23 (4. 4%) were enzyme immunoassay (EIA) positive for human immunodeficiency virus (HIV) and indeterminate by Western blot (IWB) analysis. The antibodies were mostly directed against p24 and p55 antigens. A comparison between hemodialysis patients with and without IWB showed significant differences between the two groups with respect to number of units of blood transfused, history of renal transplant rejection, and Rh status. No significant differences were observed with respect to ethnic group, nature of renal disease, duration of hemodialysis, associated diseases, and ABO blood group. The HIV IWB phenomenon may represent abnormal immune reactivity as a result of transplantation antigens and/or autoantibody formation. Five-year follow-up of the HIV EIA-positive IWB patients showed that none had seroconverted to HIV-positive status.

Salivary glands of the sand fly Phlebotomus papatasi contain pharmacologically active amounts of adenosine and 5'-AMP.

Salivary gland homogenates of the sand fly Phlebotomus papatasi contain large amounts of adenosine and 5'-AMP, of the order of 1 nmol per pair of glands, as demonstrated by liquid chromatography, ultraviolet spectrometry, mass spectrometry and bioassays. These purines, 75-80 % of which are secreted from the glands following a blood meal, have vasodilatory and anti-platelet activities and probably help the fly to obtain a blood meal. Salivary 5'-AMP is also responsible for the previously reported protein phosphatase inhibitor in the salivary glands of P. papatasi, which is shown to be artifactual in nature as a result of allosteric modification by AMP of the phosphatase substrate used (phosphorylase a).

[Myocardial reperfusion syndrome]. / Le syndrome de reperfusion myocardique.

Myocardial reperfusion is associated with a number of clinical, electrocardiographic (arrhythmias, conduction defects, ST segment changes), haemodynamic and biological events. The commonest arrhythmias are ventricular extra-systoles, rapid ventricular tachycardias, and accelerated idio-ventricular rhythms. Reperfusion bradycardias are less common. When the arrhythmia is related to ischaemia it usually regresses when perfusion is restored. Reperfusion of the inferior wall of the left ventricle is often associated with sinus bradycardia and hypotension. The ST segment changes may evolve in two different ways: progressive regression or accentuation of ST elevation. When the responsible artery is recanalized, there is an immediate rise in plasma enzyme and myoglobin concentrations. The peak CPK concentration is usually observed after the 12th hours. The diagnostic value of the reperfusion syndrome lies in the interpretation of rapid ventricular tachycardias, accelerated idio-ventricular rhythms, ST segment changes and immediate rise in plasma CPK levels. The clinical risks of the reperfusion syndrome are low, practically never rhythmic and only exceptionally haemodynamic.

[Transluminal balloon coronary angioplasty. Indications and results]. / L'angioplastie coronaire transluminale par ballonnet. Indications et résultats.

Thirteen years after its introduction transluminal balloon catheter angioplasty is a widely used technique. Owing to major technological advances and to the experience acquired by surgical teams, the primary success rate now reaches 90 p. 100. Hospital mortality has fallen down to 1 p. 100 and the need for emergency aorto-coronary bypass has been reduced to 4 p. 100 of the cases. However, despite repeated attempts at pharmacological or mechanical prevention, the restenosis rate remains around 30 p. 100. Coronary angioplasty is part of a wider strategy of myocardial reperfusion. Its indications are roughly the same as those of surgery. In patients with one-vessel coronary disease angioplasty is the first choice treatment, except for unprotected restenosis of the common trunk or very proximal lesions of the anterior interventricular artery. In multiple vessel disease the more complex the anatomical situation the more pronounced the left ventricular dysfunction and the greater the need for surgery. The acute phase of myocardial infarction is a legitimate indication for angioplasty, notably when thrombolytic agents are contraindicated or have failed when given intravenously, or in case of recurrence after an initially successful thrombolysis.

[Coronary reperfusion by anistreplase (Eminase) used intravenously during the acute phase of myocardial infarction]. / Recanalisation coronaire par l'anistreplase (Eminase) utilisée par voie intraveineuse à la phase aiguë de l'infarctus du myocarde.

Coronary recanalisation rate is one of the parameters utilized to evaluate the effectiveness of a thrombolytic agent. This parameter can only be measured when the occlusion and reopening of the coronary artery involved are demonstrated by angiography. Moreover, this type of study enables the kinetics of drug activity to be accurately determined. When injected intravenously in doses of 30 units less than four hours after the onset of chest pain and when studied by this method, Eminase produces recanalisation in more than 60 per 100 of the cases. The time elapsed between injection and action is 45 minutes on average. The risk of early reocclusion is low (about 5%). The recanalisation rate obtained with Eminase is similar to that obtained with intracoronary streptokinase.