Clinical presentation and outcomes in patients with antiphospholipid syndrome-associated adrenal hemorrhage. A multicenter cohort study and systematic literature review.

BACKGROUND: Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR). METHODS: We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis. RESULTS: We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85). CONCLUSION: AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.

Clinical features, risk factors, and outcomes of diffuse alveolar hemorrhage in antiphospholipid syndrome: A mixed-method approach combining a multicenter cohort with a systematic literature review.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disease clinically associated with thrombotic and obstetric events. Additional manifestations have been associated with APS, like diffuse alveolar hemorrhage (DAH). We aimed to summarize all the evidence available to describe the presenting clinical features, their prognostic factors, and short- and long-term outcomes. METHODS: We performed a mixed-method approach combining a multicenter cohort with a systematic literature review (SLR) of patients with incident APS-associated DAH. We described their clinical features, treatments, prognostic factors, and outcomes (relapse, mortality, and requirement of mechanical ventilation [MV]). Kaplan-Meier methods were used to estimate relapse and mortality rates, and Cox and logistic regression models were used to assess the factors associated as appropriate. RESULTS: We included 219 patients with incident APS-associated DAH (61 from Mayo Clinic and 158 from SLR). The median age was 39.5 years, 51% were female, 29% had systemic lupus erythematosus, and 34% presented with catastrophic APS (CAPS). 74% of patients had a history of thrombotic events, and 26% of women had a history of pregnancy morbidity; half of the patients had a history of thrombocytopenia, and a third had valvulopathy. Before DAH, 55% of the patients were anticoagulated. At DAH onset, 65% of patients presented hemoptysis. The relapse rate was 47% at six months and 52% at one year. Triple positivity (HR 4.22, 95% CI 1.14-15.59) was associated with relapse at six months. The estimated mortality at one and five years was 30.3% and 45.8%. Factors associated with mortality were severe thrombocytopenia (< 50 K/µL) (HR 3.10, 95% CI 1.39-6.92), valve vegetations (HR 3.22, 95% CI 1.14-9.07), CAPS (HR 3.80, 95% CI 1.84-7.87), and requirement of MV (HR 2.22, 95% CI 1.03-4.80). Forty-two percent of patients required MV on the incident DAH episode. Patients presenting with severe thrombocytopenia (OR 6.42, 95% CI 1.77-23.30) or CAPS (OR 4.30, 95% CI 1.65-11.16) were more likely to require MV. CONCLUSION: APS-associated DAH is associated with high morbidity and mortality, particularly when presenting with triple positivity, thrombocytopenia, valvular involvement, and CAPS.

Multimorbidity in systemic lupus erythematosus in a population-based cohort: the lupus Midwest network.

OBJECTIVES: To assess the prevalence and incidence of multimorbidity and the association with the SLICC/ACR damage index (SDI) among patients with systemic lupus erythematosus (SLE). METHODS: Using prevalent and incident population-based cohorts of patients with SLE and their matched comparators, we assessed 57 chronic conditions. Chronic conditions were categorized as SDI-related or SDI-unrelated. Multimorbidity was defined as the presence of 2+ chronic conditions. Multimorbidity at prevalence and incidence/index was compared between cohorts using logistic regression. Cox models were used to examine development of multimorbidity after SLE incidence. RESULTS: The prevalent cohort included 449 patients with established SLE on January 1, 2015. They were three times more likely to have multimorbidity compared with non-SLE comparators (OR 2.98, 95% CI 2.18-4.11). The incident cohort included 270 patients with new-onset SLE. At SLE incidence, patients with SLE were more likely to have multimorbidity than comparators (OR 2.27, 95% CI 1.59-3.27). After incidence, the risk of developing multimorbidity was 2-fold higher among patients with SLE than comparators (hazard ratio (HR) 2.11, 95% CI 1.59-2.80). Development of multimorbidity was higher in patients with SLE based on SDI-related (HR 2.91, 95% CI 2.17-3.88) and SDI-unrelated conditions (HR 1.73, 95% CI, 1.32-2.26). CONCLUSION: Patients with SLE have a higher burden of multimorbidity, even before the onset of the disease. The risk disparity continues after SLE classification and is also seen in a prevalent SLE cohort. Multimorbidity is driven both by SDI-related and unrelated conditions.

Postoperative inguinal pain and disability after Lichtenstein versus ONSTEP hernia repair: analysis of responses to the inguinal pain questionnaire in Spanish.

PURPOSE: To validate the Inguinal Pain Questionnaire (IPQ) in the Spanish Language and test its use in a randomized controlled trial (RCT) of hernia repair using the Lichtenstein technique vs. the ONSTEP technique. We simplified the IPQ using a principal component analysis (PCA) approach as a secondary objective. METHODS: The IPQ was translated into Spanish and validated in a cohort of 21 patients. Thereafter, 40 patients were randomized to undergo hernia repair by the Lichtenstein technique or the ONSTEP technique. IPQ and pain visual analogue (VAS) score trends over time were compared using a repeated-measures mixed-effects model. RESULTS: The Spanish version of the IPQ showed an internal consistency similar to that of the original score. No significant differences were found in the IPQ responses, pain VAS, or the rate of self-reported pain between patients who underwent the Lichtenstein technique and those who underwent the ONSTEP technique. Following PCA analysis, the number of items on the IPQ was reduced from 18 to 10. CONCLUSIONS: The Spanish version of the IPQ measures postoperative inguinal pain adequately. Based on our findings, the ONSTEP technique was not superior to the Lichtenstein technique. The simplified version of the IPQ is not significantly different from the full version and it is easier to complete. CLINICAL TRIAL REGISTRATION: NCT04138329, registered on October 24, 2019.

Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials.

OBJECTIVE: Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN). METHODS: We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes. RESULTS: Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria. CONCLUSION: A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.

New-onset microscopic polyangiitis temporally associated with severe COVID-19 infection: A case report.

The coronavirus disease 2019 has been demonstrated to be a trigger for multiple immune-mediated diseases, such as antineutrophil cytoplasmic antibody-associated vasculitis. Associated vasculitis consists of rare autoimmune disorders that predominantly affect small vessels, leading to endothelial injury and tissue damage. We present a case of a newly diagnosed microscopic polyangiitis temporally associated with coronavirus disease 2019 infection in a previously healthy woman and a literature review. A 66-year-old female presented to the Emergency Room with fever, edema on her legs, productive cough, dyspnea, and hemoptysis. A chest computerized tomography scan revealed bilateral diffuse alveolar opacities with the appearance of diffuse alveolar hemorrhage. Blood analysis revealed a moderate normocytic, normochromic anemia with a hemoglobin of 6.6 g/dL, platelet count of 347 k/dL, leucocytes of 12,000/dL, a creatinine of 3.91 mg/dL (basal Cr: 0.9 mg/dL), and a Blood Urine Nnitrogen of 78 mg/dL. A urine sediment demonstrated glomerular hematuria, with mixed shapes of red blood cells. She was admitted to the intensive care unit and a bedside bronchoscopy revealed progressive bleeding with a bronchioalveolar lavage positive for diffuse alveolar hemorrhage. Given the critical involvement of the lungs and kidney function, the diagnostic approach revealed a positive p-anti-neutrophil cytoplasmic antibody on immunofluorescence and an anti-MPO (myeloperoxidase) level of 124.6 IU/mL. A renal biopsy demonstrated pauciimmune focal and segmental glomerulosclerosis. A diagnosis of microscopic polyangiitis triggered by severe acute respiratory syndrome coronavirus 2 infection was made, and immediate treatment with pulse-dose steroids and cyclophosphamide was initiated. The patient needed renal replacement therapy and was discharged for follow-up with nephrology and rheumatology services. The diagnostic approach of associated vasculitis can be more challenging in the coronavirus disease era. Atypical features in the pulmonary imaging and a rapid deterioration of the renal function should arise the clinical suspicion of the presence of an added condition to the coronavirus disease infection. Autoimmune conditions such as associated vasculitis should be evaluated even in the absence of previous autoimmune history. Prompt diagnosis and treatments must be prioritized to avoid end-organ definite damage. Further, larger and more collaborative studies are needed to confirm the potential role of coronavirus disease 2019 as a trigger of associated vasculitis.

Aiming for zero fluid accumulation: First, do no harm.

Critically ill patients are often presumed to be in a state of "constant dehydration" or in need of fluid, thereby justifying a continuous infusion with some form of intravenous (IV) fluid, despite their clinical data suggesting otherwise. Overzealous fluid administration and subsequent fluid accumulation and overload are associated with poorer outcomes. Fluids are drugs, and their use should be tailored to meet the patient's individualized needs; fluids should never be given as routine maintenance unless indicated. Before prescribing any fluids, the physician should consider the patient's characteristics and the nature of the illness, and assess the risks and benefits of fluid therapy. Decisions regarding fluid therapy present a daily challenge in many hospital departments: emergency rooms, regular wards, operating rooms, and intensive care units. Traditional fluid prescription is full of paradigms and unnecessary routines as well as malpractice in the form of choosing the wrong solutions for maintenance or not meeting daily requirements. Prescribing maintenance fluids for patients on oral intake will lead to fluid creep and fluid overload. Fluid overload, defined as a 10% increase in cumulative fluid balance from baseline weight, is an independent predictor for morbidity and mortality, and thus hospital cost. In the last decade, increasing evidence has emerged supporting a restrictive fluid approach. In this manuscript, we aim to provide a pragmatic description of novel concepts related to the use of IV fluids in critically ill patients, with emphasis on the different indications and common clinical scenarios. We also discuss active deresuscitation, or the timely cessation of fluid administration, with the intention of achieving a zero cumulative fluid balance.