Non-myeloma light chain cast nephropathy: a multicenter retrospective study on clinicopathological characteristics.

Not available.

Non-permissive human conventional CD1c+ dendritic cells enable trans-infection of human primary renal tubular epithelial cells and protect BK polyomavirus from neutralization.

The BK polyomavirus (BKPyV) is a ubiquitous human virus that persists in the renourinary epithelium. Immunosuppression can lead to BKPyV reactivation in the first year post-transplantation in kidney transplant recipients (KTRs) and hematopoietic stem cell transplant recipients. In KTRs, persistent DNAemia has been correlated to the occurrence of polyomavirus-associated nephropathy (PVAN) that can lead to graft loss if not properly controlled. Based on recent observations that conventional dendritic cells (cDCs) specifically infiltrate PVAN lesions, we hypothesized that those cells could play a role in BKPyV infection. We first demonstrated that monocyte-derived dendritic cells (MDDCs), an in vitro model for mDCs, captured BKPyV particles through an unconventional GRAF-1 endocytic pathway. Neither BKPyV particles nor BKPyV-infected cells were shown to activate MDDCs. Endocytosed virions were efficiently transmitted to permissive cells and protected from the antibody-mediated neutralization. Finally, we demonstrated that freshly isolated CD1c+ mDCs from the blood and kidney parenchyma behaved similarly to MDDCs thus extending our results to cells of clinical relevance. This study sheds light on a potential unprecedented CD1c+ mDC involvement in the BKPyV infection as a promoter of viral spreading.

Artificial intelligence to improve cytology performance in urothelial carcinoma diagnosis: results from validation phase of the French, multicenter, prospective VISIOCYT1 trial.

PURPOSE: Cytology and cystoscopy, the current gold standard for diagnosing urothelial carcinomas, have limits: cytology has high interobserver variability with moderate or not optimal sensitivity (particularly for low-grade tumors); while cystoscopy is expensive, invasive, and operator dependent. The VISIOCYT1 study assessed the benefit of VisioCyt® for diagnosing urothelial carcinoma. METHODS: VISIOCYT1 was a French prospective clinical trial conducted in 14 centers. The trial enrolled adults undergoing endoscopy for suspected bladder cancer or to explore the lower urinary tract. Participants were allocated either Group 1: with bladder cancer, i.e., with positive cystoscopy or with negative cystoscopy but positive cytology, or Group 2: without bladder cancer. Before cystoscopy and histopathology, slides were prepared for cytology and the VisioCyt® test from urine samples. The diagnostic performance of VisioCyt® was assessed using sensitivity (primary objective, 70% lower-bound threshold) and specificity (75% lower-bound threshold). Sensitivity was also assessed by tumor grade and T-staging. VisioCyt® and cytology performance were evaluated relative to the histopathological assessments. RESULTS: Between October 2017 and December 2019, 391 participants (170 in Group 1 and 149 in Group 2) were enrolled. VisioCyt®'s sensitivity was 80.9% (95% CI 73.9-86.4%) and specificity was 61.8% (95% CI 53.4-69.5%). In high-grade tumors, the sensitivity was 93.7% (95% CI 86.0-97.3%) and in low-grade tumors 66.7% (95% CI 55.2-76.5%). Sensitivity by T-staging, compared to the overall sensitivity, was higher in high-grade tumors and lower in low-grade tumors. CONCLUSION: VisioCyt® is a promising diagnostic tool for urothelial cancers with improved sensitivities for high-grade tumors and notably for low-grade tumors.

Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 Autoantibodies.

BACKGROUND: Chronic hypomagnesemia is commonly due to diarrhea, alcoholism, and drugs. More rarely, it is caused by genetic defects in the effectors of renal magnesium reabsorption. METHODS: In an adult patient with acquired severe hypomagnesemia, hypocalcemia, tubulointerstitial nephropathy, and rapidly progressing kidney injury, similarities between the patient's presentation and features of genetic disorders of renal magnesium transport prompted us to investigate whether the patient had an acquired autoimmune cause of renal magnesium wasting. To determine if the patient's condition might be explained by autoantibodies directed against claudin-16 or claudin-19, transmembrane paracellular proteins involved in renal magnesium absorption, we conducted experiments with claudin knockout mice and transfected mouse kidney cells expressing human claudin-16 or claudin-19. We also examined effects on renal magnesium handling in rats given intravenous injections of IgG purified from sera from the patient or controls. RESULTS: Experiments with the knockout mice and in vitro transfected cells demonstrated that hypomagnesemia in the patient was causally linked to autoantibodies directed against claudin-16, which controls paracellular magnesium reabsorption in the thick ascending limb of Henle's loop. Intravenous injection of IgG purified from the patient's serum induced a marked urinary waste of magnesium in rats. Immunosuppressive treatment combining plasma exchange and rituximab was associated with improvement in the patient's GFR, but hypomagnesemia persisted. The patient was subsequently diagnosed with a renal carcinoma that expressed a high level of claudin-16 mRNA. CONCLUSIONS: Pathogenic claudin-16 autoantibodies represent a novel autoimmune cause of specific renal tubular transport disturbances and tubulointerstitial nephropathy. Screening for autoantibodies targeting claudin-16, and potentially other magnesium transporters or channels in the kidney, may be warranted in patients with acquired unexplained hypomagnesemia.

Complement Activation and Thrombotic Microangiopathy Associated With Monoclonal Gammopathy: A National French Case Series.

RATIONALE & OBJECTIVE: Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy (TMA) with kidney involvement, is a rare condition in patients with monoclonal gammopathy. In the absence of known causes of TMA, the role of complement activation in endothelial injury in patients with monoclonal gammopathy remains unknown and was the focus of this investigation. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We studied the 24 patients in the French national registry of HUS between 2000 and 2020 who had monoclonal gammopathy without other causes of secondary TMA. We provide the clinical histories and complement studies of these patients. FINDINGS: Monoclonal gammopathy-associated TMA with kidney involvement is estimated to be 10 times less frequent than adult atypical HUS (aHUS) in the French national registry. It is characterized by severe clinical features, with 17 of 24 patients requiring dialysis at disease onset, and with median renal survival of only 20 months. TMA-mediated extrarenal manifestations, particularly cutaneous and neurological involvement, were common and associated with poor overall prognosis. Complement studies identified low C3, normal C4, and high soluble C5b-9 levels in 33%, 100%, and 77% of tested patients, respectively, indicating a contribution of the alternative and terminal complement pathways in the pathophysiology of the disease. Genetic abnormalities in complement genes known to be associated with aHUS were found in only 3 of 17 (17%) who were tested. LIMITATIONS: Retrospective study without comparison group; limited number of patients, limited available blood samples. CONCLUSIONS: Within the spectrum of TMA, TMA associated with monoclonal gammopathy represents a distinct subset. Our findings suggest that HUS associated with monoclonal immunoglobulin is a complement-mediated disease akin to aHUS.

Immune alveolitis in interstitial lung disease: an attractive cytological profile in immunocompromised patients.

BACKGROUND: Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular morphological features provide additional valuable information. The significance of the "immune alveolitis" cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients' characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD. METHODS: We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD. RESULTS: Between January 2012 and December 2018, 249 patients were included. Mean age was 57 ± 16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively). CONCLUSION: Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses.

Epidemiological investigation for grouped cases of Trichosporon asahii using whole genome and IGS1 sequencing.

BACKGROUND: Trichosporonosis is a rare invasive infection in humans mainly due to Trichosporon asahii, and especially recovered from patients having haematological malignancy. Since 2012, IGS1 region sequencing is used as a genotyping method to distinguish isolates, with high frequency of one haplotype worldwide and a geographic specificity for some haplotypes. OBJECTIVES: We compared the IGS1 genotyping method and whole genome sequencing (WGS) to study the relationship between clinical isolates involved in two grouped cases in France. METHODS: IGS1 sequencing and antifungal susceptibility testing were performed for 54 clinical isolates. Clinical data for 28 isolates included in surveillance programs were analysed. Whole genome was sequenced for 32 clinical isolates and the type strain. RESULTS: All isolates were intrinsically resistant to flucytosine, while voriconazole had the most potent in vitro activity. The majority of the isolates was recovered from patients with haematological malignancies (42.86%), with a high proportion of children (<15 yrs-old, 32.14%) and a high mortality rate at three months (46.15%). Based on the WGS analysis, isolates exhibiting IGS1 haplotype 1, 3 and 7 belonged to different clades. Five isolates recovered during the first grouped cases had the same IGS1 haplotype and shared 99% of SNPs similarity. For the second grouped cases, four isolates had 98.7% of SNPs similarity while the isolate recovered 4 years earlier was totally unlinked. CONCLUSIONS: We confirmed the usefulness of IGS1 sequencing for grouped cases infection of T. asahii. We underlined its limitation for the study of population structure and the utility of WGS analysis for the study of epidemiologically unrelated isolates.

A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients.

In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66-0.92], Sp: 1.00 [95% CI: 0.86-1.00], LR+: >10, LR-: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.

Clinical Presentation, Pathological Spectrum, and Outcomes of Alcoholic Cirrhosis-Related Immunoglobulin A Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) associated with cirrhosis is frequent but often overlooked because it is largely considered silent. Until now, little has been known about their presentation and outcomes. Methods: We conducted a retrospective multicenter study on patients with kidney biopsy-proven cirrhosis-related IgAN (cirrhosis-IgAN), diagnosed between 2009 and 2022. We mixed them up with 83 primary IgAN (pIgAN) diagnosed during the same period, using a partitioning clustering approach, to determine common clinicopathological profiles. Results: All the 46 patients with cirrhosis-IgAN had an excessive alcoholic consumption. Clinical presentation was severe with acute kidney injury (AKI) in 79%; alternative causes of AKI was found in 62% of cases. Three clinicopathological clusters were identified as follows: the first one represented chronic involvement, the second one could be assimilated to mild disease, and the third one corresponded to a membranoproliferative glomerulonephritis (MPGN) pattern and was associated with heavy proteinuria and intrinsic AKI (without alternative causes). Whereas the first 2 clusters were equally distributed between pIgAN and cirrhosis-IgAN, the third was more frequent in patients with cirrhosis. The cumulative mortality rate in cirrhosis-IgAN was 26% and 46% at 1-year and 3-years, respectively. Steroid exposure and moderate or severe AKI were associated with higher mortality and steroid exposure was associated with the occurrence of severe infection. Conclusion: Our results suggest that high AKI incidence is related to extrinsic causes in most cases but can also be driven by IgA-dominant MPGN in a subset of patients. Steroid use was associated with infectious disease and mortality. Further studies are needed to clarify the role of immunosuppressive treatment in cirrhosis-IgAN patients.

Histoplasma capsulatum in Cayenne, French Guiana.

We carried out a soil sampling survey in September 2008 in central Cayenne, French Guiana, using molecular methods to assess the presence of the dimorphic fungus Histoplasma capsulatum. Four of the 31 samples collected (12.9 %) tested positive by PCR, with confirmation of the result by DNA sequencing. H. capsulatum is therefore present in urban environments in French Guiana. These results provide additional support for the primary prophylaxis of AIDS-related histoplasmosis in French Guiana.

Case Report: Invasive Cryptococcosis in French Guiana: Immune and Genetic Investigation in Six Non-HIV Patients.

Objectives: We describe the clinical, mycological, immunological, and genetic characteristics of six HIV-negative patients presenting with invasive cryptococcosis. Methods: Patients with cryptococcosis without any of the classical risk factors, such as HIV infection, followed at Cayenne Hospital, were prospectively included. An immunologic and genetic assessment was performed. Results: Five male patients and one female patient, 5 adults and one child, were investigated. All presented a neuromeningeal localization. Cryptococcus neoformans var. gattii and C. neoformans var. grubii were isolated in two and three patients, respectively, whereas one patient could not be investigated. Overall, we did not observe any global leukocyte defect. Two patients were found with high levels of circulating autoantibodies against Granulocyte macrophage-colony stimulating factor (GM-CSF), and none had detectable levels of autoantibodies against Interferon gamma (IFN-γ) Sequencing of STAT1 exons and flanking regions performed for four patients was wild type. Conclusion: To better understand cryptococcosis in patients with cryptococcosis but otherwise healthy, further explorations are needed with repeated immune checkups and strain virulence studies.

Characteristics and specificities of Cryptococcus infections in French Guiana, 1998-2008.

Cryptococcosis is a common opportunistic systemic mycosis caused by members of the encapsulated yeast genus Cryptococcus. The aetiological agents of the disease are classified into two species, i.e., Cryptococcus neoformans (serotypes A, D, and AD) affecting mainly immunocompromised patients and Cryptococcus gattii (serotypes B and C) usually found in immunocompetent individuals. Limited data exist on Cryptococcus infections in French Guiana, the department with the highest HIV incidence in the French territories. A retrospective study between January 1998 and December 2008 was performed on all patients with cryptococcosis, admitted to hospitals in French Guiana. Epidemiological data, clinical forms and diagnosis methods were studied. Of the 43 patients with cryptococcosis, 29 (67.4%) had HIV infections. Among the HIV-negative patients, two (4.7%) presented identified risk factors for cryptococcosis. This study has shown a high frequency of patients with HTLV-1 positive serology (12.1%). C. neoformans var. grubii was recovered with a frequency of 77.3% and was mainly isolated from patients with AIDS (13/17), whereas C. gattii (22.7%) was strictly isolated from HIV-negative patients with no apparent risk factors. Despite a socio-economic environment closer to western countries, the overall epidemiology of cryptococcosis in French Guiana is more similar to that found in South America, particularly with reference to the serotypes of the causative yeasts. Indeed, French Guiana presents an especially high proportion of cases caused by C. gattii, which may explain the significant incidence of this disease, particularly in HIV-negative and immunocompetent patients.

Monascus ruber: invasive gastric infection caused by dried and salted fish consumption.

We report a case of invasive gastric infection caused by Monascus ruber observed in a patient from French Guiana with gastric adenocarcinoma. The originality of this case is that, first, this invasive mycosis is extremely rare and, second, the probable mode of infection was by the consumption of Monascus ruber-contaminated food.

The triatominae species of French Guiana (Heteroptera: Reduviidae).

An annotated list of the triatomine species present in French Guiana is given. It is based on field collections carried out between 1993-2008, museum collections and a literature review. Fourteen species, representing four tribes and six genera, are now known in this country and are illustrated (habitus). Three species are recorded from French Guiana for the first time: Cavernicola pilosa, Microtriatoma trinidadensis and Rhodnius paraensis. The two most common and widely distributed species are Panstrongylus geniculatus and Rhodnius pictipes. The presence of two species (Panstrongylus megistus and Triatoma maculata) could be fortuitous and requires confirmation. Also, the presence of Rhodnius prolixus is doubtful; while it was previously recorded in French Guiana, it was probably mistaken for R. robustus. A key for French Guiana's triatomine species is provided.

Reoxygenation during radiotherapy in intermediate-risk prostate cancer.

Hypoxia is a major risk factor of prostate cancer radioresistance. We evaluated hypoxia non-invasively, using 18F-Misonidazole PET/CT prior to radiotherapy and after a dose of 20 Gy in intermediate-risk prostate cancer patients. Decreased hypoxic volumes were observed in all patients, suggesting that radiotherapy induces early prostate tumor reoxygenation.

Molecular characterization of Rhodnius robustus specimens, potential vectors for Chagas disease in French Guiana, South America.

Insects of the genus Rhodnius are broadly involved in Chagas disease transmission. In French Guiana, where the disease remains a public health problem, R. robustus and R. pictipes are vectors, but so far few genetic analyses of these local species have been reported. Here, we explored three mitochondrial genes (Cytb, Lsu-rRNA, and ND1) and one nuclear gene (D2) in 49 adult specimens morphologically characterized as R. robustus. We analyzed genetic polymorphisms and haplotype distributions, and we built phylogenetic trees using the available GenBank sequences from R. robustus and related species. The molecular taxonomy analysis confirmed that 35 insects, closely related to Brazilian species and separated by a few mutations, truly belong to R. robustus; two others were attributed to the R. prolixus complex and for 12 no sequence was obtained. The geographical haplotype distribution indicates a likely geographical structuring and evidenced true differentiation between the two main urban centers, Cayenne and Saint-Laurent-du-Maroni.

Histoplasmosis: An oral malignancy-like clinical picture.

HIV-associated histoplasmosis is mainly misdiagnosed for granulomatous diseases, such as tuberculosis. Nonetheless, malignancy-like lesions have been reported sporadically in HIV-infected patients. Although the main reported lesions are erosive or ulcerated, here a rare case of oral tumor is reported. This case raises the awareness of this presentation, and the importance of accurate identification in the laboratory. Performing systematic specific stains for fungal elements and culture on tissue samples ensures accurate differential diagnosis.

Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using 18F-fluoromisonidazole PET/CT: a pilot study.

PURPOSE: Hypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of 18F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment. MATERIALS AND METHODS: Intermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and 18F-choline-PET. 18F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation. RESULTS: Of 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUVmax and SUVmax tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml. CONCLUSIONS: This is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.