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Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
American Journal of Respiratory and... Jun 2024Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity....
Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors (MR) to promote inflammation. We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Using an established model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan) and MR (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis-generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Aldosterone was spontaneously produced by sarcoidosis PBMCs, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, PBMCs were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone or eplerenone, comparable to that of prednisone. The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses with important implications for clinical management.
PubMed: 38941161
DOI: 10.1164/rccm.202402-0265OC -
Acta Medica Philippina 2024Among pregnant women, 1-2% are anti-Ro positive and while half of them have symptoms of connective tissue disease, the rest are asymptomatic. The presence of anti-Ro is...
Among pregnant women, 1-2% are anti-Ro positive and while half of them have symptoms of connective tissue disease, the rest are asymptomatic. The presence of anti-Ro is of concern because of the risk of congenital heart block in the child. We report the case of an asymptomatic 27-year-old G2P1(1001) woman, who presented with persistent fetal bradycardia in her 21 week of gestation (AOG) and was found to have elevated titers for anti-Ro (>320 U/ml). Hydroxychloroquine 200 mg/day and prednisone 10 mg/day were given from the 33 week of gestation up until the delivery. At 37 weeks AOG, she delivered a live male neonate with a complete heart block. On the 6 day of life, the infant remained bradycardic, hence a pacemaker was inserted and heart rate maintained at 100-120 bpm. On subsequent follow-ups, the mother and child did not develop any systemic manifestations and the infant was thriving well. While a diseased condition may not be apparent in a pregnant anti-Ro positive woman, the risk of neonatal lupus (NL) is demonstrated in this patient's case. This report illustrates how prenatal care of an asymptomatic woman led to the discovery of a fetal abnormality and served to prepare the family and the medical team to ably handle the birth and subsequent care of a neonate with NL.
PubMed: 38939855
DOI: 10.47895/amp.vi0.6358 -
Cureus May 2024Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies...
Crohn's disease is a type of inflammatory bowel disease (IBD) that typically presents in the second or third decade of life. There are various pharmaceutical therapies that have been developed to treat the disease's symptoms. However, some patients still do not find relief with these medications and turn to other therapies such as diet modification. The underlying cause of Crohn's disease involves multiple factors such as uncontrolled inflammation and several genetic variants. While most current medication therapies control the symptoms that occur due to this uncontrolled level of inflammation, an anti-inflammatory diet (AID) may actually lower the level of inflammation in the gut and therefore reduce the amount of disease symptoms in Crohn's disease. Some such diets include the IBD-AID, Crohn's disease exclusion diet, and the Groningen AID (GrAID). This report describes a case of treatment-resistant Crohn's disease in a patient who was given all categories of pharmaceutical therapies including prednisone, budesonide, sulfasalazine, olsalazine, 6-mercaptopurine, methotrexate, mesalamine, and adalimumab. These only gave temporary relief of symptoms and eventually failed for various reasons including allergic reaction, insufficient symptom control, and antibody formation against the medication. This prompted the patient to independently research AIDs instead. In conclusion, for patients whose disease is refractory to different treatments, or who develop antibodies to the medication, AIDs may offer a solution to reduce disease symptoms and progression. Education of healthcare professionals and patients alike is vital in order for Crohn's patients to gain the benefits from dietary therapy.
PubMed: 38939280
DOI: 10.7759/cureus.61262 -
Case Reports in Neurological Medicine 2024Myasthenic crises (MC) are potentially life-threatening acute exacerbations of myasthenia gravis (MG) characterized by profound muscle weakness, bulbar symptoms, and...
Myasthenic crises (MC) are potentially life-threatening acute exacerbations of myasthenia gravis (MG) characterized by profound muscle weakness, bulbar symptoms, and potential for respiratory failure. Intravenous immunoglobulins (IVIG) and plasma exchange (PLEX) are conventional treatments for myasthenic exacerbations. Recently, new therapeutic options for generalized acetylcholine-receptor antibody positive (AchR+) MG were approved as an add-on therapy. They mainly consist of complement C5 inhibitors such as eculizumab and ravulizumab and neonatal Fc receptor antagonists such as efgartigimod with the approval of more options pending, e.g., zilucoplan and rozanolixizumab. More therapeutic options are in the pipeline. Although the data show a quick and reliable treatment response, these medications have not been studied for the therapy of myasthenic crisis. We present the case of a 57-year-old male with his first episode of generalized myasthenia gravis (MG) and positive acetylcholine-receptor antibodies (AchR+) who was transferred to our neurological intensive care unit with worsening generalized weakness, dysphagia, and respiratory distress. The crisis was triggered by pneumonia due to dysphagia. He was diagnosed with myasthenic crisis and treated with intravenous pyridostigmine, plasmapheresis (PLEX), and continued prednisone. Initial improvement was followed by deterioration, requiring readmission and additional PLEX. After a further decline, efgartigimod was administered, leading to significant improvement within 48 hours, as evidenced by reduced MG-ADL and QMG scores. The patient continued to improve and was stable enough for transfer to a rehabilitation facility. This case illustrates the potential of efgartigimod as a novel treatment for refractory myasthenic crises.
PubMed: 38939234
DOI: 10.1155/2024/9455237 -
CHEST Critical Care Jun 2024A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue,...
A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue, word-finding difficulties, and night sweats. The patient had a history of end-stage renal disease; he had undergone a kidney transplantation 7 years prior with good graft function with immunosuppression with tacrolimus, everolimus, and low-dose prednisone. At an outside hospital, he recently had been treated with empiric antibiotics for meningitis, but these were discontinued given the low suspicion for a bacterial cause. After discharge, he continued to have headaches, limited oral intake, persistent nausea, urinary frequency, and falls, prompting him to seek treatment at the ED. Physical examination findings were benign aside from disorientation. Laboratory workup was significant for hyponatremia of 122 mM, creatinine of 1.4 mg/dL (baseline, 1.4-1.5 mg/dL), WBC count of 7.2 10/L, hemoglobin of 13 g/dL, and platelet count of 349 10/L. Neither tacrolimus nor everolimus levels were supratherapeutic.
PubMed: 38938509
DOI: 10.1016/j.chstcc.2024.100064 -
BMC Nephrology Jun 2024Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with...
BACKGROUND
Sarcoidosis is a multisystemic inflammatory disease, characterized by the presence of non-caseating, epithelioid granulomas. Glomerular disease in patients with sarcoidosis is rare and membranous nephropathy (MN) is cited as the most common. The association between the two diseases remained unclear. This article reported a case of co-occurrence of sarcoidosis and anti-PLA2R-associated MN, to provide a possible relationship between these two entities.
CASE PRESENTATION
A 61-year-old Chinese Han woman with a history of sarcoidosis was admitted to our hospital for nephrotic syndrome. Her sarcoidosis was diagnosed according to the adenopathy observed on the computed tomography scan and the biopsy of lymph nodes. The MN presented with nephrotic syndrome with a PLA2R antibody titer of 357RU/ml, and the final diagnosis was based on a renal biopsy. The patient's sarcoidosis was remitted after treatment with prednisone. One year later MN was diagnosed, and she was treated with prednisone combined with calcineurin inhibitors, based on a full dose of renin-angiotensin system (RAS) inhibitor. The patient's sarcoidosis had been in remission while the MN was recurrent, and her renal function deteriorated to end-stage renal disease 6 years later due to discontinuation of immunosuppression. A genetic test led to the identification of the HLA-DRB1*0301 and HLA-DRB1*150 genes associated with both sarcoidosis and MN, which provides a new possible explanation of the co-occurrence of these two diseases.
CONCLUSION
This case suggested for the first time a potential genetic connection between idiopathic MN and sarcoidosis which needs further studies in the future.
Topics: Humans; Glomerulonephritis, Membranous; Female; Middle Aged; Receptors, Phospholipase A2; Sarcoidosis; Genetic Predisposition to Disease; Autoantibodies
PubMed: 38937663
DOI: 10.1186/s12882-024-03649-0 -
Infection Jun 2024Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for...
Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated.We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities.942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3-2.5]) and consecutive death (HR 1.9[1.8-2.1]). Organ and stem cell transplantation (HR 3.2[2.6-4.0] and 2.8[2.1-3.7], respectively), HIV (HR 3.2[1.9-5.4]) and systemic steroids (> 20 mg prednisone daily dose equivalent (HR 2.7[2.4-3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0-24.5]), especially HIV (HR 34.1[7.6-153]) and systemic steroids (HR 8.2[4.6-14.8]).Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.
PubMed: 38935248
DOI: 10.1007/s15010-024-02314-w -
BioDrugs : Clinical Immunotherapeutics,... Jun 2024Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the first line treatments for diffuse large B-cell lymphoma (DLBCL)....
BACKGROUND
Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the first line treatments for diffuse large B-cell lymphoma (DLBCL). Rituximab comprises most of the treatment cost for this regimen; therefore, biosimilars, such as rituximab-abbs are crucial to provide affordable care. Although rituximab-abbs was studied primarily in follicular lymphoma, the Food and Drug Administration (FDA) approved this drug for all indications of the reference product on the basis of extrapolation. Effectiveness and safety data surrounding the use of rituximab-abbs in DLBCL is lacking.
OBJECTIVE
To evaluate the effectiveness and safety of rituximab-abbs and reference product rituximab as R-CHOP treatment for patients with DLBCL.
PATIENTS AND METHODS
This noninferiority (NI) study compared the 2-year overall survival (OS), overall response rate (ORR), and incidence of adverse events (AEs) between rituximab-abbs and its reference product (RP) in R-CHOP among adult patients with newly diagnosed DLBCL. The study inclusion period was from 1 January 2019 to 31 December 2020. Analyses were performed on the basis of a noninferiority lower limit of 10% for OS and ORR, and an upper limit of 10% for serious AEs.
RESULTS
There were 240 patients who received RP rituximab, while 295 patients received rituximab-abbs. The cohort had a mean age of 63.7±12.2 years and 43% were female. The 2-year OS was 81.0% and 79.6% (NI p < 0.01) while the ORR was 80.0% and 69.6% (NI p < 0.01), among the rituximab-abbs and rituximab groups, respectively. The incidence of infusion reaction AEs (NI p < 0.01) and noninfusion reaction AEs (NI p < 0.01) also met noninferiority.
CONCLUSIONS
We demonstrated that rituximab-abbs was noninferior to rituximab in both effectiveness and safety among patients receiving R-CHOP for DLBCL in this study. Long-term follow-up would be needed to confirm these results.
PubMed: 38935234
DOI: 10.1007/s40259-024-00666-1 -
Endocrine Connections Jun 2024Prednisolone and prednisone are recommended treatment options for adults with Congenital Adrenal Hyperplasia (CAH); however, there is no randomised comparison of...
BACKGROUND
Prednisolone and prednisone are recommended treatment options for adults with Congenital Adrenal Hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone.
OBJECTIVE
To assess 17-hydroxyprogesterone (17OHP) levels and glucocorticoid dose in CAH comparing prednis(ol)one versus modified-release hydrocortisone (MRHC).
DESIGN
Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study.
METHODS
Hydrocortisone dose equivalent and 09:00h 17OHP from 48 patients taking prednis(ol)one at baseline.
RESULTS
At baseline, the median hydrocortisone dose equivalent was 30 mg /day and 17OHP was <36nmol/l (3X upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to MRHC at the same hydrocortisone equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP <36nmol/l. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg /day and 82% had 17OHP <36nmol/l. The percent of patients with 17OHP <36nmol/l on a hydrocortisone dose equivalent ≤25mg /day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P=0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years).
CONCLUSIONS
MRHC reduces 17OHP at 09:00h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.
PubMed: 38934378
DOI: 10.1530/EC-24-0150