Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort.

OBJECTIVES: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). METHODS: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. RESULTS: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26-45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3-14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2-11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11-5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31-11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). CONCLUSIONS: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.

Relevance of blood tumor markers in inpatients with significant involuntary weight loss and elevated levels of inflammation biomarkers.

PURPOSE: To assess the diagnostic performance of a panel of standard tumor markers (TMs) in patients hospitalized with significant involuntary weight loss (IWL) and elevated levels of inflammation biomarkers, and a combination of the TM panel and the finding of the computed tomography (CT) scan. METHODS: We conducted a retrospective study in the internal medicine department at Amiens-Picardie University Medical Center (Amiens, France) between January 1st, 2015, and November 1st, 2021. The inclusion criteria were age 18 or over, significant IWL (≥ 5 kg over 6 months), elevated inflammation biomarkers (e.g. C-reactive protein), and assay data on two or more standard TMs (carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19 - 9, CA 15 - 3, CA 125, neuron-specific enolase (NSE), alpha-fetoprotein (AFP), calcitonin, and prostate-specific antigen (PSA)). The result of each TM assay was interpreted qualitatively (as positive or negative), according to our central laboratory's usual thresholds. RESULTS: Cancer was diagnosed in 50 (37.0%) of the 135 patients included. Positivity for one or more TMs had a positive predictive value (PPV) of 0.55 [0.43-0.66], and a negative predictive value (NPV) of 0.84 [0.75-0.93] for cancer diagnosis. When combined with the presence of suspicious CT findings (e.g. a mass, enlarged lymph nodes and/or effusion), positivity for one or more TMs had a PPV of 0.92 [0.08-0.30]. In the absence of suspicious CT findings, a fully negative TM panel had an NPV of 0.96 [0.89-1.00]. CONCLUSION: A negative TM panel argues against the presence of a cancer, especially in the absence of suspicious CT findings.

Clonal haematopoiesis of indeterminate potential and cardiovascular events in systemic lupus erythematosus (HEMATOPLUS study).

OBJECTIVE: The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients-defining clonal haematopoiesis of indeterminate potential (CHIP)-is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. METHODS: The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. RESULTS: Screening for CHIP was performed in 438 SLE patients [38 (29-47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P < 0.00001) in SLE than in controls. The detection of CHIP at inclusion was not found to be associated with occurrence of CVEs during follow-up [HR = 0.42 (0.06-3.21), P = 0.406]. CONCLUSION: The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Highly sensitive serum cardiac troponin T and cardiovascular events in patients with systemic lupus erythematosus (TROPOPLUS study).

OBJECTIVE: Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE. METHOD: All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. RESULTS: Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99-120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31-91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan-Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE. CONCLUSION: HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.

Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study.

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed or used as self-medication in cases of community-acquired pneumonia (CAP). Nevertheless, the consequences of such medication on the risk of pleuroparenchymal complications are not well known. The aim was to investigate whether exposure to NSAIDs prior to hospital admission among patients suffering from CAP is associated with the development of pleural complications or a lung abscess. METHODS: All consecutive non-immunocompromised patients with CAP and admitted to a university hospital were prospectively included (2-year period). The risk of pleuropulmonary complications was analyzed according to previous exposure to NSAIDs. RESULTS: Of the 221 included patients, 40 (18.1%) had developed a pleuropulmonary complication. NSAIDs intake prior to admission was reported for 24 patients (10.9%) who were younger (50.6 ± 18.5 vs. 66.5 ± 16.4 years; p = 0.001), had less comorbidities (60 vs. 25.1%; p = 0.001), had a longer duration between the first symptoms of CAP and the start of an antibiotic therapy (6.1 ± 7.6 vs. 2.8 ± 3.8 days; p = 0.001), and who had a higher incidence of pleuropulmonary complications (33.3 vs. 16.2%; p = 0.048). In multivariate analyses, two factors were independently associated with the development of pleuroparenchymal complications: NSAIDs intake [Odds Ratio (OR) = 2.57 [1.02-6.64]; p = 0.049] and alcohol abuse (OR = 2.68 [1.27-5.69]; p = 0.01). CONCLUSIONS: Our findings suggest that NSAIDs, often taken by young and healthy patients, may worsen the course of CAP with delayed therapy and a higher rate of pleuropulmonary complications.

Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: a randomized clinical trial.

IMPORTANCE: Ninety percent of cases of acute calculous cholecystitis are of mild (grade I) or moderate (grade II) severity. Although the preoperative and intraoperative antibiotic management of acute calculous cholecystitis has been standardized, few data exist on the utility of postoperative antibiotic treatment. OBJECTIVE: To determine the effect of postoperative amoxicillin plus clavulanic acid on infection rates after cholecystectomy. DESIGN, SETTING, AND PATIENTS: A total of 414 patients treated at 17 medical centers for grade I or II acute calculous cholecystitis and who received 2 g of amoxicillin plus clavulanic acid 3 times a day while in the hospital before and once at the time of surgery were randomized after surgery to an open-label, noninferiority, randomized clinical trial between May 2010 and August 2012. INTERVENTIONS: After surgery, no antibiotics or continue with the preoperative antibiotic regimen 3 times daily for 5 days. MAIN OUTCOMES AND MEASURES: The proportion of postoperative surgical site or distant infections recorded before or at the 4-week follow-up visit. RESULTS: An imputed intention-to-treat analysis of 414 patients showed that the postoperative infection rates were 17% (35 of 207) in the nontreatment group and 15% (31 of 207) in the antibiotic group (absolute difference, 1.93%; 95% CI, -8.98% to 5.12%). In the per-protocol analysis, which involved 338 patients, the corresponding rates were both 13% (absolute difference, 0.3%; 95% CI, -5.0% to 6.3%). Based on a noninferiority margin of 11%, the lack of postoperative antibiotic treatment was not associated with worse outcomes than antibiotic treatment. Bile cultures showed that 60.9% were pathogen free. Both groups had similar Clavien complication severity outcomes: 195 patients (94.2%) in the nontreatment group had a score of 0 to I and 2 patients (0.97%) had a score of III to V, and 182 patients (87.8%) in the antibiotic group had a score of 0 to I and 4 patients (1.93%) had a score of III to V. CONCLUSIONS AND RELEVANCE: Among patients with mild or moderate calculous cholecystitis who received preoperative and intraoperative antibiotics, lack of postoperative treatment with amoxicillin plus clavulanic acid did not result in a greater incidence of postoperative infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01015417.

Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis.

BACKGROUND: Chronic respiratory disease and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD) increase the risk of pneumonia. Few data are available on the association of these risk factors with non-tuberculous mycobacterial (NTM) pulmonary disease. METHODS: This study examined chronic respiratory diseases and ICS use as risk factors in a population-based case-control study encompassing all adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008. The study included 10 matched population controls per case. Conditional logistic regression was used to compute adjusted ORs for NTM pulmonary disease with regard to chronic respiratory disease history. RESULTS: Overall, chronic respiratory disease was associated with a 16.5-fold (95% CI 12.2 to 22.2) increased risk of NTM pulmonary disease. The adjusted OR for NTM disease was 15.7 (95% CI 11.4 to 21.5) for COPD, 7.8 (95% CI 5.2 to 11.6) for asthma, 9.8 (95% CI 2.03 to 52.8) for pneumoconiosis, 187.5 (95% CI 24.8 to 1417.4) for bronchiectasis, and 178.3 (95% CI 55.4 to 574.3) for tuberculosis history. ORs were 29.1 (95% CI 13.3 to 63.8) for patients with COPD on current ICS therapy and 7.6 (95% CI 3.4 to 16.8) for patients with COPD who had never received ICS therapy. Among patients with COPD, ORs increased according to ICS dose, from 28.1 for low-dose intake to 47.5 for high-dose intake (more than 800 µg/day). The OR was higher for fluticasone than for budesonide. CONCLUSION: Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease.

Natural and pyrogenic humic acids at goethite and natural oxide surfaces interacting with phosphate.

Fulvic and humic acids have a large variability in binding to metal (hydr) oxide surfaces and interact differently with oxyanions, as examined here experimentally. Pyrogenic humic acid has been included in our study since it will be released to the environment in the case of large-scale application of biochar, potentially creating Darks Earths or Terra Preta soils. A surface complexation approach has been developed that aims to describe the competitive behavior of natural organic matter (NOM) in soil as well as model systems. Modeling points unexpectedly to a strong change of the molecular conformation of humic acid (HA) with a predominant adsorption in the Stern layer domain at low NOM loading. In soil, mineral oxide surfaces remain efficiently loaded by mineral-protected organic carbon (OC), equivalent with a layer thickness of ≥ ~0.5 nm that represents at least 0.1-1.0% OC, while surface-associated OC may be even three times higher. In natural systems, surface complexation modeling should account for this pervasive NOM coverage. With our charge distribution model for NOM (NOM-CD), the pH-dependent oxyanion competition of the organo-mineral oxide fraction can be described. For pyrogenic HA, a more than 10-fold increase in dissolved phosphate is predicted at long-term applications of biochar or black carbon.

2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.

Value of Positron Emission Tomography Coupled With Computed Tomography for the Diagnosis of Inflammatory Syndrome of Unknown Origin in an Internal Medicine Department.

Objective: To evaluate the usefulness of positron emission tomography (PET) coupled with computed tomography (CT) in the diagnostic workup for inflammatory syndrome of undetermined origin (IUO) and to determine the diagnostic delay in an internal medicine department. Patients and methods: We retrospectively studied a cohort of patients for whom a PET/CT scan had been prescribed in an indication of IUO in an internal medicine department (Amiens University Medical Center, Amiens, France) between October 2004 and April 2017. The patients were grouped according to the PET/CT findings: very useful (enabling an immediate diagnosis), useful, not useful, and misleading. Results: We analyzed 144 patients. The median (interquartile range) age was 67.7 years (55.8-75.8 years). The final diagnosis was an infectious disease in 19 patients (13.2%), cancer in 23 (16%), inflammatory disease in 48 (33%), and miscellaneous diseases in 12 (8.3%). No diagnosis was made in 29.2% of the cases; half of the remaining had a spontaneously favorable outcome. Fever was observed in 63 patients (43%). Positron emission tomography coupled with CT was determined to be very useful in 19 patients (13.2%), useful in 37 (25.7%), not useful in 63 (43.7%), and misleading in 25 (17.4%). The median diagnostic delay (ie, the time interval between the first admission and a confirmed diagnosis) was significantly shorter in the useful (71 days [38-170 days]) and very useful (55 days [13-79 days]) groups than that in the not useful group (175 days [51-390 days]; P<.001). The median time interval between the PET/CT scan and the diagnosis was twice as long in the not useful group than that in the pooled misleading, useful, or very useful groups (P=.03). In a univariate analysis, the poor overall condition (P=.007) and the absence of fever (P=.005) were predictive of usefulness of PET/CT. Conclusion: Positron emission tomography coupled with CT seems to be useful in the diagnosis of IUO and might shorten the diagnostic delay.

Inhaled corticosteroids and adverse outcomes among chronic obstructive pulmonary disease patients with community-acquired pneumonia: a population-based cohort study.

Introduction: While inhaled corticosteroids (ICS) may increase pneumonia risk in patients with chronic obstructive pulmonary disease (COPD), the impact of ICS on pneumonia outcomes is debated. We examined whether ICS use is associated with adverse outcomes among COPD patients with community-acquired pneumonia (CAP). Materials and methods: Population-based cohort study of all COPD patients with an incident hospitalization for CAP between 1997 and 2013 in Northern Denmark. Information on medications, COPD severity, comorbidities, complications, and death was obtained from medical databases. Adjusted risk ratios (aRRs) for pleuropulmonary complications, intensive care unit (ICU) admissions, and 30-day mortality in current and former ICS users were compared with those in non-users, using regression analyzes to handle confounding. Results: Of 11,368 COPD patients with CAP, 6,073 (53.4%) were current ICS users and 1,733 (15.2%) were former users. Current users had a non-significantly decreased risk of pleuropulmonary complications [2.6%; aRR = 0.82 (0.59-1.12)] compared to non-users (3.2%). This was also observed among former users [2.5%; aRR = 0.77 (0.53-1.12)]. Similarly, decreased risks of ICU admission were observed among current users [aRR = 0.77 (0.57-1.04)] and among former users [aRR = 0.81 (0.58-1.13)]. Current ICS users had significantly decreased 30-day mortality [9.1%; aRR = 0.72 (0.62-0.85)] compared to non-users (12.6%), with a stronger association observed among patients with frequent exacerbations [0.58 (0.39-0.86)]. No significant association was observed among former ICS users [0.89 (0.75-1.05)]. Conclusion: Our results suggest a decreased risk of death with ICS use among COPD patients admitted for CAP.

Deep Learning on Bone Scintigraphy to Detect Abnormal Cardiac Uptake at Risk of Cardiac Amyloidosis.

BACKGROUND: Cardiac uptake on technetium-99m whole-body scintigraphy (WBS) is almost pathognomonic of transthyretin cardiac amyloidosis. The rare false positives are often related to light-chain cardiac amyloidosis. However, this scintigraphic feature remains largely unknown, leading to misdiagnosis despite characteristic images. A retrospective review of all WBSs in a hospital database to detect those with cardiac uptake may allow the identification of undiagnosed patients. OBJECTIVES: The authors sought to develop and validate a deep learning-based model that automatically detects significant cardiac uptake (Perugini grade ≥2) on WBS from large hospital databases in order to retrieve patients at risk of cardiac amyloidosis. METHODS: The model is based on a convolutional neural network with image-level labels. The performance evaluation was performed with C-statistics using a 5-fold cross-validation scheme stratified so that the proportion of positive and negative WBSs remained constant across folds and using an external validation data set. RESULTS: The training data set consisted of 3,048 images: 281 positives (Perugini grade ≥2) and 2,767 negatives. The external validation data set consisted of 1,633 images: 102 positives and 1,531 negatives. The performance of the 5-fold cross-validation and external validation was as follows: 98.9% (± 1.0) and 96.1% for sensitivity, 99.5% (± 0.4) and 99.5% for specificity, and 0.999 (SD = 0.000) and 0.999 for the area under the curve of the receiver-operating characteristic curves. Sex, age <90 years, body mass index, injection-acquisition delay, radionuclides, and the indication of WBS only slightly affected performances. CONCLUSIONS: The authors' detection model is effective at identifying patients with cardiac uptake Perugini grade ≥2 on WBS and may help in the diagnosis of patients with cardiac amyloidosis.

2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.

The systemic capillary leak syndrome: a case series of 28 patients from a European registry.

BACKGROUND: The systemic capillary leak syndrome (SCLS) is a rare disease characterized by life-threatening attacks of capillary hyperpermeability. OBJECTIVE: To describe the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. DESIGN: Case series. SETTING: Patients referred to a European multicenter SCLS registry between January 1997 and July 2010. PATIENTS: 28 patients with SCLS. MEASUREMENTS: Frequency, severity of attacks, and vital status were assessed every 6 months, from diagnosis to the end of the study. RESULTS: 13 men and 15 women referred to the registry who were not previously reported in the literature had 252 attacks. Median age at disease onset was 49.1 years (range, 5.4 to 77.7 years), and median annual frequency of attacks was 1.23 (range, 0.13 to 21.18) per patient. Monoclonal IgG gammopathy was observed in 25 patients (89%). Preventive treatment included intravenous immunoglobulin (n = 18), terbutaline (n = 9), and aminophylline (n = 10). Eight patients died (29%); 1-year survival was 89%, and 5-year survival was 73%. Death was directly related to SCLS attacks in 6 of 8 cases (75%). In 10 patients with a prediagnosis period greater than 6 months who received preventive treatment, the annual frequency of attacks after diagnosis decreased by a median of 1.55 (range, 0.14 to 8.84) per patient. Five years after diagnosis, survival was 85% in 23 patients who had received prophylactic treatment and 20% in 5 patients who had not. LIMITATION: The benefits of preventive treatment could not be precisely ascertained because of the small sample size and because most patients received several treatments. CONCLUSION: Clinical experience with these 28 patients with SCLS suggests that prophylactic treatment with ß(2)-agonists or intravenous immunoglobulin may reduce the frequency and severity of attacks and may improve survival. PRIMARY FUNDING SOURCE: Université Pierre et Marie Curie, Paris, France.

Prognostic factors of Pasteurella infections: a single-center retrospective cohort study over a 14-year period (2005-2018).

BACKGROUND: Pasteurella spp. can lead to fatal infections in humans. OBJECTIVE: To assess prognostic factors of invasive pasteurellosis. METHODS: We conducted a single retrospective cohort study of local versus invasive Pasteurella infections from January 1, 2005, to December 31, 2018, in the Amiens-Picardie University Hospital, France. RESULTS: Forty-five (20.9%) invasive pasteurellosis and 22 (10.2%) complicated local infections were reported among a total of 215 Pasteurella infections. The mortality rate among invasive infections was 22.2% (10/ 45) whereas no death was recorded in local infections group. Non-drug-induced prothrombin time test <70% of standard and platelet counts <100,000/mm3 were more frequent in non-survivors than in survivors (p=0.005 and p=0.019) in univariate analyses. A history of neoplasia (adjusted OR=13.62, p=0.020), an evidence of bacteremia (adjusted OR=20.68, p=0.025), and hemoglobin level <10 g/dL (adjusted OR=17.80, p=0.028) were identified as poor prognostic factors in multivariate analyses. CONCLUSION: Invasive pasteurellosis appears as a serious disease in vulnerable patients, particularly if bacteremia and/or coagulopathies occur.

COVID-19 in DMARD-treated patients with inflammatory rheumatic diseases: Insights from an analysis of the World Health Organization pharmacovigilance database.

BACKGROUND: To determine whether the use of disease-modifying antirheumatic drugs (DMARDs) is linked to the risk of COVID-19 among patients with inflammatory rheumatic diseases (IRDs). METHODS: We performed a disproportionality analysis of the World Health Organization pharmacovigilance database between January 1, 2020, and June 10, 2020. The frequency of COVID-19 reports for all DMARD classes identified was compared with that for all other reports for all other drugs and quoted as the reporting odds ratio (ROR) (95% confidence interval [CI]). RESULTS: Among 980,446 individual case-safety reports voluntarily recorded in the database, 398 identified COVID-19 in DMARD-treated patients with IRDs. There were 177 (44.5%) patients with rheumatoid arthritis (RA), 120 (30.1%) with ankylosing spondylitis (AS), 93 (23.4%) with psoriatic arthritis (PsA), and 8 (2.0%) with juvenile idiopathic arthritis. Most of the cases of COVID-19 occurred in patients taking anti-TNF agents (84.2%), resulting in a significant disproportionality signal (ROR [95% CI]: 8.31 [7.48-9.23]) - particularly in patients with RA, AS or PsA. A significant inverse disproportionality was found for the anti-IL-6 agent tocilizumab (ROR [95% CI]: 0.12 [0.02-0.88]) and JAK inhibitors (ROR [95% CI]: 0.33 [0.19-0.58]) in patients with RA - suggesting that these two drug classes are safer in the context of RA. CONCLUSION: Our results are in line with the literature on a potentially better safety profile for anti-IL-6 agents and JAK inhibitors. The WHO pharmacovigilance data suggest that COVID-19 is significantly more frequent in patients with IRDs treated with TNF inhibitors.

Cutaneous involvement in relapsed multiple myeloma.

Cutaneous involvement in multiple myeloma with extramedullary disease is rare. We report the case of a refractory multiple myeloma patient who developed a cutaneous lesion. Histopathology revealed dermal immature plasma cell infiltrate with a lack of CD138 expression. This cutaneous location was associated with an aggressive clinical course and short survival.

Nontuberculous pulmonary mycobacteriosis in Denmark: incidence and prognostic factors.

RATIONALE: Few population-based data are available regarding nontuberculous mycobacteria (NTM) pulmonary disease epidemiology and prognosis. OBJECTIVES: To examine NTM pulmonary colonization incidence, disease incidence, and prognostic factors. METHODS: All adults in Denmark with at least one NTM-positive pulmonary specimen during 1997 to 2008 were identified using national medical databases and were categorized as having possible or definite NTM disease or colonization. MEASUREMENTS AND MAIN RESULTS: We calculated annual age-standardized NTM incidence rates and adjusted hazard ratios (HR) of death associated with patient age, sex, comorbidity, NTM species, and NTM disease status. Of 1,282 adults with 2,666 NTM-positive pulmonary specimens, 335 (26%) had definite NTM disease, 238 (19%) possible disease, and 709 (55%) colonization only. NTM incidence rates decreased until 2002, followed by an increase from 2003 to 2008 (mean annual rate per 100,000 person-years: NTM colonization, 1.36; NTM disease, 1.08). Five-year mortality after definite NTM disease was 40.1%. After controlling for potential confounders, 5-year mortality for definite NTM disease was slightly higher than for NTM colonization (adjusted hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.90-1.51). Mycobacterium xenopi was associated with worse prognosis (adjusted HR, 1.51; 95% CI, 0.99-2.33) than the reference Mycobacterium avium complex. High comorbidity level (HR, 2.97), age greater than or equal to 65 years (HR, 9.17), and male sex (female sex HR, 0.73) were predictors of death. CONCLUSIONS: NTM disease incidence has remained unchanged in Denmark over the past 12 years. Patients with NTM colonization and disease have similarly poor prognosis. Negative prognostic factors include high levels of comorbidity, advanced age, male sex, and M. xenopi.