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AME Case Reports 2024Non-small cell lung cancer (NSCLC) has a high incidence of lung cancer, with a 30% incidence of KRAS mutations and a low 5-year survival rate. Until the Food and Drug...
BACKGROUND
Non-small cell lung cancer (NSCLC) has a high incidence of lung cancer, with a 30% incidence of KRAS mutations and a low 5-year survival rate. Until the Food and Drug Administration (FDA) approved sotorasib in May 2021, no therapies targeted mutated in cancer. Sotorasib, a new inhibitor, is currently recognized as the newest clinically targeted agent with apparent clinical efficacy in NSCLC patients with mutations. FDA approval is required for patients with advanced or metastatic NSCLC undergoing at least one chemotherapy regimen.
CASE DESCRIPTION
In our study, we report a patient with advanced NSCLC combined with brain metastases, clinical stage IV (c.T3N0M1b), (+) detected by next-generation sequencing (NGS) technology, direct use of sotorasib, an inhibitor of , as first-line therapy. The patient was treated with 4 months of oral therapy, had significant partial remission (PR), and remained in stable disease (SD) for nearly 9 months of follow-up, with no other side effects. Further extension of the follow-up period is needed to assess the impact of sotorasib as first-line therapy on patient survival. A series of clinical trials in phase 3 is ongoing, covering the first-line usage widespread.
CONCLUSIONS
Based on the literature review, this is the first domestic report in China where sotorasib was used directly as first-line treatment in patients with advanced combined brain metastasis from NSCLC. It needs a longer follow-up to evaluate the efficacy of sotorasib further as a first-line.
PubMed: 38711902
DOI: 10.21037/acr-23-153 -
Kidney International Reports May 2024Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of...
INTRODUCTION
Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome.
METHODS
We retrospectively reviewed clinicopathologic features of NELL1 MN from 3 institutions and analyzed clinical and histologic associations with outcome.
RESULTS
Of 70 patients, 53% were male with a median age of 66 years; median proteinuria was 5.9 g/d. NELL1 MN was associated with lipoic acid (36%), heavy nonsteroidal antiinflammatory drug (NSAID) use (27%), autoimmune disease (23%), malignancy (10% recent, 23% any), mercury exposure (1%), and 11% had no known secondary association. At median follow-up of 11 months, 72% achieved complete or partial remission. Remission rate was 91% in patients with lipoic acid-associated NELL1 MN and ≥6 months of follow-up. On multivariable analyses, patients with primary NELL1 MN (adjusted odds ratio [OR]: 19.7, = 0.01) and increasing degree of tubular atrophy and interstitial fibrosis (IFTA) (adjusted OR 1.1, = 0.01) were less likely to achieve any remission, whereas complete remission (CR) was associated with lipoic acid use (adjusted OR: 10.9, = 0.04, 95% confidence interval [CI]: 1.2-100) and lesser degrees of IFTA (adjusted OR: 0.79, = 0.16, 95% CI: 0.66-0.96).
CONCLUSION
Our findings strengthen the association between lipoic acid and NELL1 MN. Furthermore, our findings suggest that discontinuation of lipoic acid without immunosuppression should be considered as the first-line treatment.
PubMed: 38707817
DOI: 10.1016/j.ekir.2024.02.1401 -
Leukemia Research Reports 2024Orbital plasmacytoma is rare and has only been reported in the context of the initial diagnosis of multiple myeloma. Moreover, isolated orbital plasmacytoma without any...
Orbital plasmacytoma is rare and has only been reported in the context of the initial diagnosis of multiple myeloma. Moreover, isolated orbital plasmacytoma without any signs of multiple myeloma is extremely rare. We report the case of a 59-year-old female patient diagnosed with IgA Kappa multiple myeloma. It was stage I ISS (International Staging System) and stage I R-ISS (Revised ISS). According to the Tunisian national protocol, the patient was included in the standard-risk group and was eligible for four cycles of CTD (Cyclophosphamide, Thalidomide, Dexamethasone) followed by autologous stem cell transplantation. Taking into account the partial response after the CTD cycles, the patient has benefited from two VTD cycles (Bortezomib, Thalidomide, Dexamethasone). Thus, complete remission was obtained. The patient refused autologous stem cell transplantation. Therefore, maintenance treatment based on Thalidomide only was started and received over a twelve-month period. Five months after the end of maintenance treatment, she reported frontal headaches that were resistant to symptomatic treatment, with ptosis in the right eye in physical examination. Brain MRI revealed the presence of a right cranio-orbital tissue mass with intra-orbital and extra-axial cerebral components. The mass measured 32/36 mm on axial sections and 47 mm in height. The patient underwent a complete resection of the cranio-orbital mass with cranioplasty. The histopathological examination of the mass with Immunohistochemistry staining confirmed the diagnosis of orbital plasmocytoma. An update of the multiple myeloma assessment did not reveal any biological, cytological or radiological signs in favor of multiple myeloma. Therefore the diagnosis of isolated orbital plasmacytoma without signs of multiple myeloma was made. Post-operative brain MRI showed complete disappearance of the right cranio-orbital tissue lesion. There was only a persistent meningeal enhancement of the dura mater at the surgical site, suggestive of post-operative changes. The patient was then referred for cranio-orbital radiotherapy.
PubMed: 38707773
DOI: 10.1016/j.lrr.2024.100460 -
JCEM Case Reports May 2024We report the first case of imatinib use in an adolescent with diabetes and suggest that it impacts the natural course of disease. A 14-year-old male patient presented...
We report the first case of imatinib use in an adolescent with diabetes and suggest that it impacts the natural course of disease. A 14-year-old male patient presented in diabetic ketoacidosis (DKA) and was diagnosed with presumed autoantibody-negative type 1 diabetes (T1D) as well as myeloid neoplasm with platelet-derived growth factor receptor beta (PDGFRB) rearrangement. After starting exogenous insulin and imatinib, he experienced a 1.7-point reduction in glycated hemoglobin (HbA1c) and a 71% reduction in insulin requirement with sustained partial diabetes remission. Our case suggests imatinib as a potential therapeutic agent for pediatric T1D.
PubMed: 38707652
DOI: 10.1210/jcemcr/luae065 -
Journal of Medical Case Reports May 2024Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment...
BACKGROUND
Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment varies according to its underlying cause but often faces medication resistance or adverse drug effects.
CASE PRESENTATION
A Japanese woman in her 80s presented with nephrotic syndrome after a 3 year latent period of urinary protein and occult blood. She did not have any secondary causes of nephrotic syndrome. Renal biopsy revealed thin glomerular basement membrane, partial foot process fusion on electron microscopy with minor glomerular change on light microscopy, and slight coarse immunoglobulin M deposition in the mesangium on immunofluorescence microscopy, which was inconsistent with any other glomerular diseases. Without steroid treatment, she dramatically remitted from proteinuria after the administration of the renal protective agents enalapril, ezetimibe, rosuvastatin, and dapagliflozin. Recurrence after 8 months of follow-up subsided with the administration of additional doses of the agents.
CONCLUSIONS
This case illustrated the novel outcomes of combining medical treatment without steroid use for nephrotic syndrome with thin glomerular basement membrane disease. At the time of writing this report, the patient's renal function was stable and she was free of edema, although moderate proteinuria and occult hematuria persisted. The final diagnosis was uncertain because of the lack of genetic investigation; however, the response to the aforementioned medical treatment suggests the effectiveness of the supportive therapy.
Topics: Humans; Nephrotic Syndrome; Female; Aged, 80 and over; Proteinuria; Glomerular Basement Membrane; Remission Induction; Treatment Outcome
PubMed: 38702831
DOI: 10.1186/s13256-024-04564-6 -
BMC Pediatrics Apr 2024X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are...
BACKGROUND
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA.
CASE PRESENTATION
In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria.
CONCLUSIONS
In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.
Topics: Humans; Agammaglobulinemia; Male; Glomerulonephritis, IGA; Genetic Diseases, X-Linked; Child; Immunoglobulins, Intravenous; Glucocorticoids; Mycophenolic Acid; Immunosuppressive Agents
PubMed: 38689221
DOI: 10.1186/s12887-024-04746-7 -
Cancer Medicine May 2024To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens.
Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.
OBJECTIVE
To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens.
METHODS
This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity.
RESULTS
The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia.
CONCLUSION
In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.
Topics: Humans; Boron Compounds; Male; Glycine; Multiple Myeloma; Middle Aged; Female; Aged; Retrospective Studies; Proteasome Inhibitors; Bortezomib; Adult; Antineoplastic Combined Chemotherapy Protocols; Administration, Oral; China; Aged, 80 and over
PubMed: 38686615
DOI: 10.1002/cam4.7177 -
Journal of Clinical Medicine Apr 2024: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially...
: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel therapeutic approaches. We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR). The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L, = 0.037). The present study could benefit from a larger sample size. We did not assess dietary habits. The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.
PubMed: 38673634
DOI: 10.3390/jcm13082361 -
Biomedicines Mar 2024The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This... (Review)
Review
INTRODUCTION
The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This systematic review aims to elucidate the effects of iMN recurrence on graft survival.
MATERIALS AND METHODS
A literature search was performed by systematically searching Medline, Scopus, Web of Science, and Google Scholar from inception. Cohort studies examining iMN recurrence after kidney transplantation were deemed eligible. Meta-analysis was performed by fitting random-effects models.
RESULTS
Twelve (12) articles published from 1995 to 2016 reporting on 139 transplant patients with recurrent iMN were included. The median time of the diagnosis of recurrent iMN was 18 months during follow-up from 35 to 120 months. Risk factors for iMN recurrence in the renal allograft are a positive serum test for anti-PLA2R antibodies pretransplant, female sex, younger age, high proteinuria pretransplant, the longest interval from initial disease to end-stage chronic kidney disease, and the combination of alleles HLA DQA1 05:01 and HLA DQB1 02:01. In the pretransplant period, 37 (26.61%) patients had a positive serum test and 18 (12.94%) patients had a positive biopsy stain for anti-PLA2R antibodies. The sensitivity of the pretransplant positive serum test for these antibodies ranges from 57% to 85.30% and the specificity is 85.10-100%. A total of 81.80% of patients who received rituximab as treatment for iMN recurrence achieved complete and partial remission, while 18.20% had no response to treatment. iMN recurrence was not associated with significantly different rates of graft loss (odds ratio = 1.03, 95% CI: 0.52-2.04, = 0.524, I = 0.00%). Recurrence of iMN was not associated with increased risk of graft loss independently of whether patients were treated with rituximab (OR: 0.98, 95% CI: 0.39-2.50, I: 0%) or not (OR: 1.22, 95% CI: 0.58-2.59, I: 3.8%). Patients with iMN recurrence who achieved remission had significantly reduced risk of graft loss (OR: 0.14, 95% CI: 0.03 to 0.73).
CONCLUSION
The main outcome from this systematic review is that there is no statistically significant difference in graft survival in patients with iMN recurrence compared to those without recurrence in long-term follow-up. The achievement of remission is associated with significantly reduced risk of graft loss.
PubMed: 38672095
DOI: 10.3390/biomedicines12040739 -
Hepatic Medicine : Evidence and Research 2024This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient,...
This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII-VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII-VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient's survival time was 16 months.
PubMed: 38660476
DOI: 10.2147/HMER.S449206