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Journal of Community Hospital Internal... 2023Methotrexate is a commonly prescribed immunosuppressant and chemotherapy agent, which is closely monitored by healthcare providers for its adverse effects. As a result,...
Methotrexate is a commonly prescribed immunosuppressant and chemotherapy agent, which is closely monitored by healthcare providers for its adverse effects. As a result, methotrexate toxicity occurs infrequently. We present a case of a 51-year-old woman with a past medical history of rheumatoid arthritis on methotrexate and prednisone. She presented to the emergency room with altered mental status, jaundice, and mucosal ulceration. She was subsequently admitted to the intensive care unit for septic shock in the setting of severe pancytopenia, acute renal failure and acute liver failure. This case demonstrates the importance of recognizing the signs and symptoms of methotrexate toxicity due to its infrequent presentation.
PubMed: 38596556
DOI: 10.55729/2000-9666.1255 -
Cureus Mar 2024Linezolid plays a clinically important role; however, it is responsible for severe pharmacological interactions and side effects, such as myelosuppression, serotonin...
Linezolid plays a clinically important role; however, it is responsible for severe pharmacological interactions and side effects, such as myelosuppression, serotonin syndrome, and lactic acidosis. We report a case of an 80-year-old man treated with venlafaxine for depression. He was admitted with a right femur fracture and submitted to surgical intervention, complicated by local infection. In collected pus was identified multiple microorganisms including resistant to vancomycin. The therapeutic was adjusted to linezolid. On the 36 day of treatment, he developed hypertension, poor peripheral perfusion, and generalized tremor. He was disoriented, with marbled skin, myoclonus, and sinus tachycardia; and apyretic, with no signs of respiratory distress or joint/surgical wound inflammatory signs. Blood tests showed hyperlacticemia and discrete elevation of C-reactive protein but in a decrescent trend, with no other relevant alterations. The diagnosis of lactic acidosis and probable serotonin syndrome secondary to linezolid was made, supported by improvement after the drug suspension.
PubMed: 38586704
DOI: 10.7759/cureus.55672 -
Oncology Letters May 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare and aggressive tumor with an unknown pathogenesis. Myelofibrosis (MF) is a type of...
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare and aggressive tumor with an unknown pathogenesis. Myelofibrosis (MF) is a type of myeloproliferative neoplasm. MF can be secondary to several hematological malignancies, including chronic myeloid leukemia, myelodysplastic syndrome and hairy cell leukemia. In the present report, a rare case of BPDCN secondary to MF is described. A 70-year-old male patient developed a large purplish-red rash with recurrent symptoms. BPDCN was confirmed by immunohistochemistry of a biopsy specimen and flow cytometry of bone marrow cells. Bone marrow histopathology revealed MF. Next-generation sequencing of peripheral blood revealed mutations in the Tet methylcytosine dioxygenase 2 and NRAS proto-oncogene GTPase genes. The patient underwent one cycle of chemoimmunotherapy, but the condition progressed, an infection developed and the patient eventually died. The present case suggests that BPDCN can occur in conjunction with MF and that the prognosis of such patients is poor. Pathological examination and genetic testing aided in the diagnosis and treatment. This case emphasizes the need to raise awareness of BPDCN among clinicians and to be alert to the potential for fatal infection in patients with BPDCN combined with MF following myelosuppression triggered during chemotherapy.
PubMed: 38586204
DOI: 10.3892/ol.2024.14354 -
Clinical and Experimental Medicine Apr 2024Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in... (Review)
Review
Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.
Topics: Humans; Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Lung; Off-Label Use; Quinazolines; Retrospective Studies; Transplant Recipients
PubMed: 38578337
DOI: 10.1007/s10238-024-01330-2 -
World Journal of Clinical Cases Mar 2024The prognosis for patients with advanced metastatic cervix cancer (MCC) is poor, and this disease continues to pose a considerable therapeutic challenge. Despite the...
BACKGROUND
The prognosis for patients with advanced metastatic cervix cancer (MCC) is poor, and this disease continues to pose a considerable therapeutic challenge. Despite the administration of first-line regimens consisting of cisplatin, paclitaxel, and bevacizumab, survival rates for patients with metastasis remain poor. The emergence of bispecific antibodies (BsAbs) offers a novel treatment option for patients diagnosed with MCC.
CASE SUMMARY
In this report, we present a patient with MCC who was treated with cadonilimab monotherapy at a dose of 6 mg/kg every two weeks after chemotherapy was proven to be intolerable. The patient exhibited a sustained complete response for a duration of 6 months, demonstrating an optimistic outlook.
CONCLUSION
This case illustrates the considerable efficacy of cadonilimab for treating advanced MCC. Therefore, BsAb therapy is a promising strategy for effectively treating patients with advanced MCC and should be considered as an option when patients are intolerant to standard chemotherapy.
PubMed: 38576806
DOI: 10.12998/wjcc.v12.i8.1510 -
Heliyon Mar 2024Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by...
Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic , exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma.
PubMed: 38545201
DOI: 10.1016/j.heliyon.2024.e28070 -
Life (Basel, Switzerland) Feb 2024Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects....
Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects. To overcome DOX limitations, two novel pyridoxine-derived doxorubicin derivatives were synthesized (DOX-1 and DOX-2). In the present study, their antitumor activity and mechanism of action were investigated. Of these two compounds, DOX-2, in which the pyridoxine fragment is attached to the doxorubicin molecule via a C3 linker, revealed higher selectivity against specific cancer cell types compared to doxorubicin and a promising safety profile for conditionally normal cells. However, the compound with a C1 linker (DOX-1) was not characterized by selectivity of antitumor action. It was revealed that DOX-2 obstructs cell cycle progression, induces apoptosis via the mitochondrial pathway without the development of necrosis, and showcases antioxidant capabilities, underlining its cell-regulatory roles. In contrast to doxorubicin's DNA-centric mechanism, DOX-2 does not interact with nuclear DNA. Given these findings, DOX-2 presents a new promising direction in cancer therapeutics, which is deserving of further in vivo exploration.
PubMed: 38541608
DOI: 10.3390/life14030282 -
Leukemia Research Reports 2024To investigate the short-term efficacy and safety of different chemotherapy regimens combined with thalidomide, in the treatment of low-income patients with newly... (Review)
Review
OBJECTIVE
To investigate the short-term efficacy and safety of different chemotherapy regimens combined with thalidomide, in the treatment of low-income patients with newly diagnosed HIV-associated diffuse large B-cell lymphoma.
METHODS
A retrospective analysis was performed on 42 patients with HIV-DLBCL who were admitted to the Infectious Diseases Department of Yunnan Provincial Infectious Diseases Hospital from January 2018 to December 2020. 14 cases (including 1 case in stage II and 13 cases in stage III/IV) were treated with R-CHOP, 24 cases (including 1 case in stage II and 23 cases in stage III/IV) were treated with R-DAEPOCH, and 4 cases (including 1 case in stage II and 3 cases in stage III/IV) were treated with EPOCH. All patients were treated with thalidomide. The ART regimen was adjusted. At least 1 and up to 6 intrathecal injections were given during chemotherapy, and cotrimoxazole was taken orally to prevent infection. The clinical efficacy was evaluated after 4 cycles of chemotherapy, and adverse events were evaluated at each cycle of chemotherapy.
RESULTS
All patients received 1-8 cycles of chemotherapy. CR (64.2 %) was achieved in 9 patients in R-CHOP group, and 5 patients died. In the R-DAEPOCH group, 17 patients achieved CR (70.8 %) and 7 died. In the EPOCH group, 2 patients reached CR (50 %) and 2 died. The main adverse reactions were grade II and above myelosuppression.
CONCLUSION
Combined treatment with thalidomide can improve the prognosis of low-income patients with newly diagnosed HIV-DLBCL.
PubMed: 38516379
DOI: 10.1016/j.lrr.2024.100450 -
Critical Care Explorations Feb 2024Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently...
Ruxolitinib, IV Immunoglobulin, and High-Dose Glucocorticoids for Critically Ill Adults With Secondary Hemophagocytic Lymphohistiocytosis: A Single-Center Observational Pilot Study.
OBJECTIVES
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a cytokine-driven inflammatory syndrome that is associated with substantial morbidity and mortality and frequently leads to ICU admission. Overall survival in adults with sHLH remains poor, especially in those requiring intensive care. Classical chemotherapeutic treatment exhibits myelosuppression and toxicity. Recently, inhibition of Janus kinase signaling by ruxolitinib has shown efficacy in pediatric HLH. We therefore aimed to determine the activity and safety of a ruxolitinib-based regimen, in critically ill adults with sHLH.
DESIGN
Observational pilot study.
SETTING
Single-center tertiary academic ICU.
PATIENTS
Nine adults (≥ 18 yr) who fulfilled at least five of the eight HLH-2004 criteria.
INTERVENTION
Triplet regimen combining: 1) ruxolitinib, 2) polyvalent human IV immunoglobulins (IVIG) at a dose of 1 g/kg bodyweight for 5 days, and 3) high-dose corticosteroids (CSs, dexamethasone 10 mg/m² body surface area, or methylprednisolone equivalent) with subsequent tapering according to the HLH-2004 protocol.
MEASUREMENT AND MAIN RESULTS
Nine patients (median age: 42 yr [25th-75th percentile: 32-54]; male: = 6 males, median H-score: 299 [255-304]) were treated with the triplet regimen. The median Sequential Organ Failure Assessment score at HLH diagnosis was 9 (median; 25th-75th percentile: 7-12), indicating multiple-organ dysfunction in all patients. Within 10 days a significant decrease of the inflammatory parameters soluble interleukin-2 receptor and ferritin as well as a stabilization of the blood count could be shown. All patients were alive at ICU discharge (100% ICU survival), 1 patient died after ICU discharge because of traumatic intracerebral hemorrhage that might be related to HLH or treatment, corresponding to an overall survival of 86% in a 6 months follow-up period.
CONCLUSION
In this small case series, a triplet regimen of ruxolitinib in combination with IVIG and CS was highly effective and save for treating critically ill adults with sHLH.
PubMed: 38511127
DOI: 10.1097/CCE.0000000000001046 -
Neuro-oncology Practice Apr 2024Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are...
BACKGROUND
Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).
METHODS
A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers.
RESULTS
A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease.
CONCLUSIONS
GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.
PubMed: 38496907
DOI: 10.1093/nop/npad067