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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 -
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 -
Life (Basel, Switzerland) Jun 2024Sarcoidosis, characterized by non-caseating epithelioid granulomas, presents diagnostic and therapeutic challenges.
BACKGROUND
Sarcoidosis, characterized by non-caseating epithelioid granulomas, presents diagnostic and therapeutic challenges.
METHOD
Here we present a 38-year-old woman who exhibited erythematous and infiltrated skin lesions on her facial region following fractional laser treatment.
RESULTS
Histological analysis confirmed cutaneous sarcoidosis. Initial interventions with topical clobetasol and oral chloroquine provided transient relief. Subsequent outpatient management comprised topical tacrolimus and clobetasol, as well as systemic methotrexate, later substituted with prednisone. Gradual tapering resulted in lesion reduction.
CONCLUSIONS
This case underscores the intricate nature of cutaneous sarcoidosis and the necessity for personalized therapeutic approaches. The association with cosmetic procedures highlights the importance of understanding potential triggers. The presented case highlights and reminds the medical community that lasers are not only used for therapeutic purposes but can also induce specific responses through laser therapy. Notably, while laser therapy is frequently employed in treating cutaneous sarcoidosis, its role in inducing sarcoidosis warrants further investigation.
PubMed: 38929755
DOI: 10.3390/life14060773 -
Frontiers in Neurology 2024To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).
PURPOSE
To describe the early experience of ravulizumab use in acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ve gMG).
METHODS
This multicenter retrospective study included AChR+ve gMG patients who were treated with ravulizumab and had both pre- and post-ravulizumab myasthenia gravis activities of daily living (MG-ADL) scores. Clinical information regarding MG history, concomitant treatment(s), MG-ADL, other MG-specific measures, and adverse events were recorded.
RESULTS
A total of 18 patients with mean age of 61.83 (±16.08, = 18) years were included in this cohort. In 10 complement inhibitor naive patients, a clinically meaningful reduction in mean Mg-ADL (baseline: 6.6 (±3.58) vs. 4.4 (±2.28), post ravulizumab) was seen. 6 out of 10 patients (60%) had clinically meaningful reduction post ravulizumab and two achieved minimum symptom expression (MSE). In 8 patients switched from eculizumab to ravulizumab, further reduction was noted in post ravulizumab mean MG-ADL (Baseline: 3.25 (±3.34) vs. 1.5 (±2.34) post ravulizumab). None of the patients who switched from eculizumab to ravulizumab experienced worsening symptoms. Eleven out of 14 (78.5%) patients on prednisone therapy were able to reduce their prednisone dose post-ravulizumab. None of the patients experienced any major side effects.
CONCLUSION
In our clinical practice, 60% of AChR+ve gMG complement inhibitor naive patients experienced a clinically meaningful improvement in MG-ADL scores with ravulizumab. Patients were safely switched from eculizumab to ravulizumab and had further improvement in their mean MG-ADL scores. Of those on prednisone therapy, the majority were able to reduce their prednisone dosage.
PubMed: 38919970
DOI: 10.3389/fneur.2024.1378080 -
Frontiers in Oncology 2024Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), also known as MALT lymphoma, is an extranodal multiorgan-invasive proliferative lymphoma...
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), also known as MALT lymphoma, is an extranodal multiorgan-invasive proliferative lymphoma composed of small B cells with variable morphology. It most commonly occurs in the digestive tract, with a high prevalence in the stomach, but EMZL originating in the small intestine is rare and lacks specificity in clinical manifestations, which makes it easy to be misdiagnosed. Herein, we report a rare case of small intestinal EMZL presentation as intussusception in a 32-year-old man. A colonoscopy performed at the local hospital revealed a pedicled polyp about 5 cm × 5 cm in size with a rough surface, and hyperemia was seen in the ileocecal region. He was admitted to our hospital for a polypectomy. A contrast-enhanced computed tomographic (CT) scan suggested ileocolic intussusception, which was subsequently confirmed by a colonoscopy in our hospital. Adult intussusception is relatively rare, with 90% of cases having a known causative mechanism and 40% of cases caused by primary or secondary malignancies. Therefore, we performed a laparoscopic-assisted right hemicolectomy for the patient. The resected specimen showed that the terminal ileum was intussuscepted into the ascending colon, and the intussusception was hyperemia and edema. A 2.5 cm × 2.5 cm × 1.5 cm mass was seen at the end of the intussusception. Postoperative pathology revealed that the mass was EMZL, partially transformed into a large B-cell lymphoma. The patient was transferred to the hematology department and completed a PET-CT showing postoperative manifestations of primary intestinal lymphoma, Lugano staging IE2. Although EMZL was an indolent lymphoma and the patient was in the early stages, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen was given in view of the histological transformation. The patient is in regular follow-up. This was a rare case of small intestinal mass due to EMZL presented as intussusception in adults, which highlighted laparoscopic-assisted enterectomy as a potential therapeutic approach in the multidisciplinary collaborative therapy of small intestine EMZL.
PubMed: 38919535
DOI: 10.3389/fonc.2024.1395144 -
Rheumatology Advances in Practice 2024Translating the highly technical medical jargon of SLE into understandable concepts for patients, their families and individuals without expertise in SLE is a serious...
OBJECTIVE
Translating the highly technical medical jargon of SLE into understandable concepts for patients, their families and individuals without expertise in SLE is a serious challenge. To facilitate communication and enable self-management in SLE, we aimed to create an innovative visual tool, the Purple Butterfly.
METHODS
We selected clinically representative criteria for SLE and transposed them as graphical features in an attractive and meaningful visual. We developed a script in R programming language that automatically transposes clinical data into this visualization. We asked SLE patients from a local cohort about the relevance, usefulness and acceptability of this visual tool in an online pilot survey.
RESULTS
The innovative Purple Butterfly features 11 key clinical criteria: age; sex; organ damage; disease activity; comorbidities; use of antimalarials, prednisone, immunosuppressants and biologics; and patient-reported physical and mental health-related quality of life. Each Purple Butterfly provides the health portrait of one SLE patient at one medical visit, and the automatic compilation of the butterflies can illustrate a patient's clinical journey over time. All survey participants agreed that they would like to use the Purple Butterfly to visualize the course of their SLE over time, and 9 of 10 agreed it should be used during their medical consultations.
CONCLUSION
The Purple Butterfly nurtures effective doctor-patient communication by providing concise visual summaries of lupus patients' health conditions. We believe the Purple Butterfly has the potential to empower patients to take charge of their condition, enhance healthcare coordination and raise awareness about SLE.
PubMed: 38915844
DOI: 10.1093/rap/rkae075 -
JAMIA Open Jul 2024Electronic health record textual sources such as medication signeturs (sigs) contain valuable information that is not always available in structured form. Commonly...
IMPORTANCE
Electronic health record textual sources such as medication signeturs (sigs) contain valuable information that is not always available in structured form. Commonly processed through manual annotation, this repetitive and time-consuming task could be fully automated using large language models (LLMs). While most sigs include simple instructions, some include complex patterns.
OBJECTIVES
We aimed to compare the performance of GPT-3.5 and GPT-4 with smaller fine-tuned models (ClinicalBERT, BlueBERT) in extracting the average daily dose of 2 immunomodulating medications with frequent complex sigs: hydroxychloroquine, and prednisone.
METHODS
Using manually annotated sigs as the gold standard, we compared the performance of these models in 702 hydroxychloroquine and 22 104 prednisone prescriptions.
RESULTS
GPT-4 vastly outperformed all other models for this task at any level of in-context learning. With 100 in-context examples, the model correctly annotates 94% of hydroxychloroquine and 95% of prednisone sigs to within 1 significant digit. Error analysis conducted by 2 additional manual annotators on annotator-model disagreements suggests that the vast majority of disagreements are model errors. Many model errors relate to ambiguous sigs on which there was also frequent annotator disagreement.
DISCUSSION
Paired with minimal manual annotation, GPT-4 achieved excellent performance for language regression of complex medication sigs and vastly outperforms GPT-3.5, ClinicalBERT, and BlueBERT. However, the number of in-context examples needed to reach maximum performance was similar to GPT-3.5.
CONCLUSION
LLMs show great potential to rapidly extract structured data from sigs in no-code fashion for clinical and research applications.
PubMed: 38915730
DOI: 10.1093/jamiaopen/ooae051 -
PloS One 2024Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua...
BACKGROUND
Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification.
METHODS
The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments.
RESULTS
A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1β, STAT3, MMP-9, and TGF-β1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-β1/Smad2/3.
CONCLUSIONS
QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-β1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.
Topics: Pulmonary Fibrosis; Drugs, Chinese Herbal; Animals; Rats; Male; Network Pharmacology; Protein Interaction Maps; Bleomycin; Transforming Growth Factor beta1; Rats, Sprague-Dawley; Signal Transduction; Humans; COVID-19; Epithelial-Mesenchymal Transition; Medicine, Chinese Traditional; COVID-19 Drug Treatment
PubMed: 38913698
DOI: 10.1371/journal.pone.0305903 -
Open Life Sciences 2024Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL)...
Richter transformation (RT) represents the development of intrusive lymphoma in individuals previously or concurrently diagnosed with chronic lymphocytic leukemia (CLL) and is characterized by lymph node enlargement. However, cases involving extra-nodal organ involvement as the first symptom are rare. There are no reports of RT with breast lesions as the first symptom. Nonspecific and atypical clinical manifestations represent key challenges in the accurate diagnosis and appropriate treatment of RT. This case report describes an elderly female patient who presented with breast lesions as the first RT symptom. The patient was admitted with a painless mass in the left breast. Examination revealed multiple lymphadenopathies and abnormally high white blood cell levels. The patient was diagnosed with CLL after hematological tests, assessments of bone marrow morphology, and tissue biopsy. Mammography and B-ultrasonography showed solid space-occupying lesions (BI-RADS category 5) in the left breast. Initially, the patient declined a breast biopsy and was therefore prescribed ibrupotinib treatment, which showed limited efficacy. A needle biopsy of the affected breast indicated the presence of diffuse large B-cell lymphoma. Based on auxiliary and pathological examinations and medical history, the final diagnosis was RT with breast involvement. Zanubrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment provided initial control; however, the treatment strategy required adjustment because of the patient's fluctuating condition. The current status of the patient is marked as stable, showing an overall achievement of partial alleviation. The patient is in the process of receiving follow-up treatment. We also performed a comprehensive literature review on RT, with particular emphasis on its biological paradigm, prognosis implications, existing therapeutic approaches, and emerging directions in treatment modalities.
PubMed: 38911930
DOI: 10.1515/biol-2022-0889 -
Pediatric Investigation Jun 2024It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A...
IMPORTANCE
It remained unclear that the efficacy comparison between low-dose immune tolerance induction (LD-ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor-titer ≥200 Bethesda Units (BU)/mL (LD-ITI-IS regimen) and LD-ITI combining with IS when SHA patients had inhibitor-titer ≥40 BU/mL (LD-ITI-IS regimen).
OBJECTIVE
To compare the efficacy of the LD-ITI-IS regimen with that of the LD-ITI-IS regimen for SHA patients with high-titer inhibitors.
METHODS
A prospective cohort study on patients receiving LD-ITI-IS compared to those receiving LD-ITI-IS from January 2021 to December 2023. Both received LD-ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD-ITI-IS regimen and ≥40 BU/mL in the LD-ITI-IS regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected.
RESULTS
We enrolled 30 patients on LD-ITI-IS and 64 patients on LD-ITI-IS, with similar baseline clinical characteristics. A lower IS-use rate was discovered in the LD-ITI-IS regimen compared to the LD-ITI-IS regimen (30.0% vs. 62.5%). The two regimens (LD-ITI-IS vs. LD-ITI-IS) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD-ITI-IS than for LD-ITI-IS (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor-titer 40-199 BU/mL, 10 non-IS-using (on LD-ITI-IS regimen) and 28 IS-using (on LD-ITI-IS regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months).
INTERPRETATION
In LD-ITI, IS are not necessary for inhibitor titer <200 BU/mL.
PubMed: 38910855
DOI: 10.1002/ped4.12429