Benralizumab for eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series. METHODS: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day. RESULTS: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004). CONCLUSIONS: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.

Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients.

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched PubMed and EMBASE up to 20 August 2020 to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of intensive care unit admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RRs), and 95% confidence intervals (CIs) were calculated using a random-effects model. Thirty-four adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14 of 34 adult studies included only hospitalized patients). Risk of death among adult patients was 34% (95% CI, 28-39; N = 3240) in this sample of predominantly hospitalized patients. Patients aged ≥60 years had a significantly higher risk of death than patients <60 years (RR, 1.82; 95% CI, 1.45-2.27; N = 1169). The risk of death in pediatric patients was 4% (95% CI, 1-9; N = 102). RR of death comparing patients with recent systemic anticancer therapy to no treatment was 1.17 (95% CI, 0.83-1.64; N = 736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients ≥60 years have significantly higher mortality; pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death.

The role of PET/CT in large vessel vasculitis and related disorders: diagnosis, extent evaluation and assessment of therapy response.

Large vessel vasculitides (LVV) are defined as chronic inflammatory disorders that affect the arteries with two major variants being distinguished: giant cell arteritis (GCA) and Takayasu's arteritis (TAK). These often present with nonspecific constitutional symptoms which makes an accurate diagnosis often challenging. Nevertheless, timely diagnosis is of utmost importance to initiate treatment and to avoid potential life-threatening complications. [18F]FDG-PET/CT is nowadays widely accepted as useful tool to aid in the diagnosis of large vessel vasculitis. However, its role to monitor disease activity and to predict disease relapse during follow-up is less obvious since vascular [18F]FDG uptake can be detected in the absence of clinical or biochemical signs of disease activity. In addition to the two major variants, [18F]FDG-PET/CT has shown promise in (peri-)aortitis and related disorders. This article aims to provide an update on the current knowledge and limitations of [18F]FDG-PET/CT for the diagnosis and assessment of treatment response in LVV. Furthermore, other radiopharmaceuticals targeting key components of the vascular immune system are being discussed which could provide an interesting alternative to image vascular inflammation in LVV.

The effect of empagliflozin on P wave peak time and other P wave parameters in patients with diabetes mellitus.

BACKGROUND: Empagliflozin is a selective SGLT2 inhibitor and provides a significant reduction in hospitalizations in heart failure patients and a reduction in combined cardiovascular deaths regardless of diabetes. The mechanisms of favorable effects remain unclear. Improvement in left ventricular diastolic function and a decrease in filling pressure are any mechanisms of positive effects. These effects may show themselves with some changes on the electrocardiography (ECG). So, we aimed to evaluate the effect of empagliflozin on P wave parameters in type 2 diabetes mellitus patients without HF. METHOD: Fifty-three patients were included in the study. The electrocardiographic and echocardiographic evaluations were examined at the baseline and end of the third month for all patients. RESULTS: The median age of all patients was 55 (45-64 IQR). After treatment, LA volume (p <.001) and diameter (p = .001) in both the parasternal long-axis (p = .001) and the apical four-chamber view decreased. E/e' and systolic pulmonary arterial pressure were significantly decreased after treatment. P wave duration max,min, PWDmin, and PWdis were significantly shorter after treatment. The P wave peak time (PWPT) in lead Dii and V1 were significantly shorter after treatment. CONCLUSION: We found shortening of PWPT, PWdis, and PWD as reflections of improvements in left atrial volume and LV diastolic function on ECG after empagliflozin treatment.

Determinants of IgG antibodies kinetics after severe and critical COVID-19.

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.

A case report of cutaneous leishmaniasis: a misleading clinical presentation.

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

SARS-CoV-2 causes a specific dysfunction of the kidney proximal tubule.

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome.

An unusual case of cardiac tamponade: Bronchogenic cyst infection due to Salmonella bredeney.

We present an unusual case of cardiac tamponade in a 17-year-old girl immunocompetent patient due to Salmonella enterica ssp. bredeney following infection of a bronchogenic cyst. The patient was admitted to hospital with pleuritic chest pain, dyspnoea and fever. Pulmonary angio-CT showed a bronchogenic cyst compressing the left atrium. The echocardiography showed diffuse pericardial effusion with right ventricular collapse consistent with cardiac tamponade. Pericardiocentesis was performed and microbiological cultures of the pericardial fluid became positive for Salmonella species confirmed later as bredeney subspecies by PCR. Empirical antibiotherapy was started with intravenous (IV) ceftriaxone. Bronchogenic cyst infection was suspected and confirmed by 18FDG PET CT. The patient was successfully treated by complete resection of the cyst and continuation of IV ceftriaxone followed by oral amoxicillin/clavulanate for a total duration of 6 weeks. She then completely recovered and didn't present any relapse after 6 months of follow up.

Mortality in patients with high risk Staphylococcus aureus bacteremia undergoing or not PET-CT: A single center experience.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Previous studies had shown that PET/CT can be helpfull in the management of SAB, leading to reduction of mortality. Factors associated with increased or reduced mortality are not well known. Our objective was to analyze mortality in high risk SAB patients undergoing PET/CT and to identify factors associated with mortality rate. MATERIALS AND METHODS: We performed a retrospective study and reviewed all cases of high risk adult SAB between 2014 and 2017. We analyzed medical records and mortality at 30 days and 90 days and 1 year. RESULTS: A total of 102 patients were included in whom 48 undergone PET/CT. Metastatic foci was identified in 45.8% of cases (22/48). The overall mortality rate was 31.4% (32/102). The mortality rate was 16.6% (8/48) and 44.4% (24/54) in patients undergoing or not PET/CT respectively (P = 0.002). There was a signicantly difference in mortality rate at 30 days (P = 0.001), 90 days (P = 0.004) and one at 1 year (P = 0.002) between patients undergoing or not PET/CT respectively. In multivariate analysis only 18-FDGPET/CT, kidney failure and bacteremia of unknown origin were the 3 mains factors modifying mortality in patients with high risk SAB. CONCLUSION: In our study mortality rate was reduced in high risk SAB patients undergoing PET/CT. kidney failure and bacteremia of unknown origin were other factors associtated with high mortality. Our study confirm that PET/CT is a usefull tool in the management of SAB.

Lymphocyte-to-monocyte ratio is a valuable marker to predict prostate cancer in patients with prostate specific antigen between 4 and 10 ng/dl.

OBJECTIVE: To evaluate the diagnostic value of serum inflammation markers derived from complete blood count in diagnosis of prostate cancer (PCa). METHODS: We retrospectively analyzed the data of 621 patients who underwent prostate biopsy between March 2013 and April 2018. Age, prostate specific antigen (PSA), free PSA, platelet count, neutrophil count, lymphocyte count, monocyte count, prostate volume (PV) and pathology result of the patients were recorded. Patients were grouped as benign prostatic hyperplasia (BPH), prostatitis and PCa. Patients were also grouped according to PSA values, as PSA < 4 , PSA 4-10 and PSA > 10 ng/dl. RESULTS: The mean lymphocyte-to-monocyte ratio (LMR) value of the patients with PCa was significantly lower in the entire cohort (p = 0.047). In the PSA 4-10 ng/dl range, LMR value wassignificantly lower in patients with PCa than those with BPH or prostatitis (p = 0.012). In this PSA range, free/total PSA ratio and LMR were significant factors to predict PCa. The cut-off values of LMR, free/total PSA were 3.05 and 0.15 respectively. The sensitivities, spesificities, positive predictive values (PPV) and negative predictive values using LMR cut-off, free/total PSA cut-off and their combination were assessed. Specificity and PPV of the combination group were higher (97.2%, 83.3% respectively) compared to free/total PSA cut-off group (91.6%, 76.6%) and LMR cut-off group (67.8%, 43.7%). CONCLUSIONS: LMR is a useful tool at detecting PCa especially in patients with PSA value between 4 and 10 ng/dl. The combination of free/total PSA ratio and LMR improves the diagnostic accuracy more than the use of free/total PSA ratio alone.

TINU-associated Fanconi syndrome: a case report and review of literature.

BACKGROUND: Tubulo-interstitial Nephritis and Uveitis (TINU) syndrome is a rare oculo-renal inflammatory disease. Renal tubular defects are usually found, but full proximal tubular abnormalities have rarely been described. CASE PRESENTATION: We report the case of a 55-year old woman, native from Morocco, presenting with bilateral, non-granulomatous, anterior uveitis, mild renal insufficiency, leucocyturia and glycosuria. Further work-up showed hypophosphatemia and hyperphosphaturia, hypouricemia and hyperuricosuria, and hyper aminoaciduria, consistent with Fanconi syndrome. A kidney biopsy was obtained and showed diffuse interstitial infiltrates with tubular necrosis. The patient improved after the initiation of a corticosteroid therapy, with tapering dose. CONCLUSIONS: We reviewed the literature and found nine similar cases. This association mostly occurs in adult woman, without current evidence for an ethnic predilection, unlike previously reported. The renal prognosis seems favorable after corticosteroid therapy, even in case of severe renal injury. Nonetheless mild tubular defects may persist after treatment or spontaneous remission.

Man with bilateral inguinal lymphadenopathy.

CLINICAL INTRODUCTION: A 37-year-old man with history of lymph node tuberculosis presented with bilateral inguinal swelling with night sweats but no fever for 2 weeks. He had a cat but he had no history of scratches. He had an extraconjugal sexual intercourse a few weeks before. Physical examination revealed 5 cm tender, erythematous and painful bilateral inguinal adenopathy (figure 1A) and a small ulceration at the base of the penis (figure 1B). Vital signs were normal.emermed;35/8/522/F1F1F1Figure 1(A) Inguinal lymphadenopathy. (B) Ulceration at the base of the penis. QUESTION: What is the most likely diagnosis?ToxoplasmosisTuberculosisCat-scratch diseaseLymphogranuloma venereumSyphilis.

Acute pyelonephritis and renal vein thrombosis: A case report and review of the literature.

A 68-year-old female presented with a week history of fever and generalized weakness. Clinical examination, blood work and urinalysis were compatible with sepsis due to acute pyelonephritis. Urine cultures were positive for Escherichia coli and blood cultures were negative. After 5 days of antibiotic therapy with cefuroxime, inflammatory parameters (CRP level and white blood cell count) remained highly elevated. Abdominal CT scan showed right kidney pyelonephritis with renal and perirenal abscess and right renal vein thrombosis. The patient improved after percutaneous drainage of the perirenal abscess and anticoagulation treatment. She was discharged on hospital day 14.

Malignant rhabdoid tumour in the stomach.

In this case report, a rare tumoral morphology in the gastrointestinal system is introduced. Malignant rhabdoid features are rarely observed in the gastrointestinal system but this discrimination is important due to the tumor's poor prognosis, aggressive behavior and early metastasis.

A Comparison Study of Lymph Node Tuberculosis and Sarcoidosis Involvement to Facilitate Differential Diagnosis and to Establish a Predictive Score for Tuberculosis.

Background: Tuberculosis (TB) and sarcoidosis are two common granulomatous diseases involving lymph nodes. Differential diagnosis is not always easy because pathogen demonstration in tuberculosis is not always possible and both diseases share clinical, radiological and histological patterns. The aim of our study was to identify factors associated with each diagnosis and set up a predictive score for TB. Methods: All cases of lymph node tuberculosis and sarcoidosis were retrospectively reviewed. Demographics, clinical characteristics, laboratory and imaging data, and microbiological and histological results were collected and compared. Results: Among 441 patients screened, 192 patients were included in the final analysis. The multivariate analysis showed that weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia were significantly associated with TB. A risk score of TB was built based on these variables and was able to discriminate TB versus sarcoidosis with an AUC of 0.85 (95% CI: 0.79-0.91). Using the Youden's J statistic, its most discriminant value (-0.36) was associated with a sensitivity of 80% and a specificity of 75%. Conclusions: We developed a score based on weight loss, necrotic granuloma, normal serum lysozyme level and hypergammaglobulinemia with an excellent capacity to discriminate TB versus sarcoidosis. This score needs still to be validated in a multicentric prospective study.

Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes. METHODS: In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes. RESULTS: The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; p = 0.002/p < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; p = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL. DISCUSSION: The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.