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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.
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Background: Cancer is a leading cause of death for people worldwide, in addition to the rise in mortality rates attributed to the Covid epidemic. This allows scientists to do additional research. Here, we have selected Integerrimide A, cordy heptapeptide, and Oligotetrapeptide as the three cyclic proteins that will be further studied and investigated in this context.Methods: Docking research was carried out using the protein complexes 1FKB and 1YET, downloaded from the PDB database and used in the docking investigations. Cyclopeptides have been reported to bind molecularly to human HSP90 (Heat shock protein) and FK506. It was possible to locate HSP90 in Protein Data Banks 1YET and 1FKB. HSP90 was retrieved from Protein Data Bank 1YET and 1FKB. Based on these findings, it is possible that the anticancer effects of Int A, Cordy, and Oligo substances could be due to their ability to inhibit the mTOR rapamycin binding domain and the HSP90 Geldanamycin binding domain via the mTOR and mTOR chaperone pathways. During the calculation, there were three stages: system development, energy reduction, and molecular dynamics (also known as molecular dynamics). Each of the three compounds demonstrated a binding affinity for mTOR's Rapamycin binding site that ranged from -6.80 to -9.20 Kcal/mol (FKB12).Results: An inhibition constant Ki of 181.05 nM characterized Cordy A with the highest binding affinity (-9.20 Kcal/mol). Among the three tested compounds, Cordy A was selected for MD simulation. HCT116 and B16F10 cell lines were used to test each compound's anticancer efficacy. Doxorubicin was used as a standard drug. The cytotoxic activity of substances Int A, Cordy A, and Oligo on HCT116 cell lines was found to be 77.65 μM, 145.36 μM, and 175.54 μM when compared to Doxorubicin 48.63 μM, similarly utilizing B16F10 cell lines was found to be 68.63 μM, 127.63 μM, and 139.11 μM to Doxorubicin 45.25 μM.Conclusion: Compound Cordy A was more effective than any other cyclic peptides tested in this investigation.
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Introduction: IgA vasculitis is more commonly seen in the pediatric population than in adults. Rarely IgA vasculitis is associated with malignancy, most commonly solid tumor malignancies, although there are case reports of association with hematologic malignancies. We report a case of large B-cell lymphoma mimicking IgA vasculitis in a 33-year-old immunosuppressed male with a prior history of IgA vasculitis. Case Description/Methods: A 33-year-old Caucasian male post renal transplant from reflux nephropathy on chronic immunosuppression was hospitalized for postprandial epigastric abdominal pain, nausea, vomiting and diarrhea. Two years prior, he was admitted for the same symptoms, palpable purpura of the lower extremities and elevated serum IgA. Enteroscopy had shown duodenal and jejunal ulceration with biopsies staining positive for IgA, confirming IgA vasculitis. He had complete resolution with a steroid taper. His current presentation had resulted in multiple hospital admissions, but empiric trial of steroids failed to alleviate symptoms. Vitals were normal and exam was notable for epigastric tenderness. Labs were notable for WBC 19.00 x103/cmm with normal differential, hemoglobin 9.2 gm/dL (prior 11.0 gm/dL), CRP 20.7 mg/L, serum creatinine 2.7 mg/dL (prior 1.5 mg/dL), and urinalysis with proteinuria, sterile pyuria, and hematuria. CTA abdomen/pelvis revealed thickening of the duodenum with shotty mesenteric lymph nodes without ischemia. Enteroscopy revealed an erythematous duodenum and jejunum (figure A). Jejunal biopsy (figure B) revealed CD20 positive cells consistent with DLCBL (figure C). He was seen by oncology and treated with R-CHOP but later unfortunately expired due to COVID-19 complications. Discussion(s): Non small cell lung cancer and renal cell carcinoma are most commonly associated with IgA vasculitis. It may also be seen in both Hodgkin and Non-Hodgkin lymphomas in adult patients. If IgA vasculitis occurs after a malignancy is diagnosed, it may indicate that metastasis has occurred. Malignancy associated IgA vasculitis is more likely to have an incomplete response to steroids and requires treatment of the underlying malignancy to achieve remission. Our case illustrates posterior probability error and premature closure cognitive biases. We should consider alternative diagnoses rather than anchor on prior diagnoses even when presentations are similar. Our case also highlights the importance of considering occult malignancy in adults with diagnosis of IgA vasculitis.
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Introduction: Drug repurposing is an effective strategy for identifying the use of approved drugs for new therapeutic purposes. This strategy has received particular attention in the development of cancer chemotherapy. Considering that a growing body of evidence suggesting the cholesterol-lowering drug ezetimibe (EZ) may prevent the progression of prostate cancer, we investigated the effect of EZ alone and in combination with doxorubicin (DOX) on prostate cancer treatment. Methods: In this study, DOX and EZ were encapsulated within a PCL-based biodegradable nanoparticle. The physicochemical properties of drug containing nanoparticle based on PCL-PEG-PCL triblock copolymer (PCEC) have been exactly determined. The encapsulation efficiency and release behavior of DOX and EZ were also studied at two different pHs and temperatures. Results: The average size of nanoparticles (NPs) observed by field emission scanning electron microscopy (FE-SEM) was around 82±23.80 nm, 59.7±18.7 nm, and 67.6±23.8 nm for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively, which had a spherical morphology. In addition, DLS measurement showed a monomodal size distribution of around 319.9, 166.8, and 203 nm hydrodynamic diameters and negative zeta potential (-30.3, -6.14, and -43.8) mV for EZ@PCEC, DOX@PCEC, and DOX+EZ@PCEC NPs, respectively. The drugs were released from the NPs sustainably in a pH and temperature-dependent manner. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the PC3 cell line. Therefore, PCEC was a biocompatible and suitable nano-vehicle for this study. The cytotoxicity of the DOX-EZ-loaded NPs on the PC3 cell line was higher than that of NPs loaded with single drugs. All the data confirmed the synergistic effect of EZ in combination with DOX as an anticancer drug. Furthermore, fluorescent microscopy and DAPI staining were performed to show the cellular uptake, and morphological changes-induced apoptosis of treated cells. Conclusion: Overall, the data from the experiments represented the successful preparation of the nanocarriers with high encapsulation efficacy. The designed nanocarriers could serve as an ideal candidate for combination therapy of cancer. The results corroborated each other and presented successful EZ and DOX formulations containing PCEC NPs and their efficiency in treating prostate cancer.
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.
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The proceedings contain 63 papers. The topics discussed include: doxorubicin cardiotoxicity in human organotypic cardiac slices is modulated by P38 MAPK inhibition in a sex- and isoform-specific manner;validation of a modified response evaluation criteria in solid tumors after stereotactic ablative radiosurgery for lung cancer;safer use of aspirin in older adults, need for a consensus;efficacy of facemasks in prevention of COVID-19: a systematic review;practice patterns of rapid influenza diagnostic test;equity and inclusion in patient centered outcomes research: lessons from the adaptable study at Montefiore site;a solution to decrease potentially inappropriate medications (PIM) use during hospitalization;predictors of misperceptions, risk perceptions, and personal risk perceptions about COVID-19 by country, education and income;cognitive function and the consumption of probiotic foods in older adults: an NHANES study;and registered dietitian nutritionist care impacts nutrition-related outcomes for patients with cancer in the outpatient setting.
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Case report Background: Association of chronic spontaneous urticaria (CSU) with malignancies and worsening of urticaria during COVID-19 have been reported. The efficacy of treatment of CSU with omalizumab in the context of malignancies or COVID-19 is not well established. Method(s): Case report of a patient followed for 9 years with CSU. Data collected from Medical Records and interviews during consultations. Result(s): Female, 29 years-old, came to clinic in 2013 for investigation, diagnosed with CSU. She also presented mild asthma, allergic rhinitis and history of urticaria after taking amoxicillin. She had a positive autologous serum skin test, and positive skin tests to dust mite, cat, cockroach, peanut and milk. Her total IgE was 227IU/ mL. Anti-nuclear and anti-thyroid antibodies were negative;ERS 13mm, blood eosinophils 300/mm3, and stool exam negative for parasites. She showed no response to second generation antihistamines up to fourfold doses, with UCT < 6 and CU-QoL = 89. After 6 months, omalizumab was added at 300 mg subcutaneously, every 4 weeks. The patient showed immediate reactions after the two applications of omalizumab: first, diffuse pruritus and throat tightness;second, worsening of urticaria and pruritus, requiring iv medications. Treatment with omalizumab was stopped, she was kept on fourfold dose of bilastine with partial control of symptoms. In 2016, she presented worsening of urticaria (UCT = 1), weight loss of 6kg/2 months, daily fever and enlarged cervical lymph nodes, and was diagnosed with diffuse large B-cell non-Hodgkin's lymphoma. Following chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab, she presented complete resolution of urticaria. Two years after remission of the lymphoma, in 2019, she presented recurrence of urticaria, and treatment with fourfold dose of bilastine was reinitiated with control of symptoms (UCT = 16). Investigation ruled out recurrence of lymphoma. In May 2021, she was diagnosed with SARS-CoV- 2 infection. Symptoms of COVID-19 were runny nose and low grade fever, however urticaria got worse and no longer responsive to bilastine. Treatment with omalizumab was attempted, with no reactions and good efficacy after the first dose, with an UCT = 15, and urticaria remains controlled on treatment with omalizumab to present. Conclusion(s): In this report, we highlight the efficacy and safety of using omalizumab in a patient with refractory CSU associated with neoplasia and SARS-CoV- 2 infection.
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Since Coronavirus Disease 2019 (COVID-19) was declared pandemic in March 2020, there have been 545.226.550 cases up to 4 July 2022 (1). Several studies concluded that patients (pts) with cancer are at increased risk of COVID-19 infection, morbidity and mortality. Those undergoing neoadyuvant treatment are at particularly risk of disease progression if chemotherapy or surgery are delayed. Also, is known that a higher NLR (neutrophil to limphocyte ratio) is related to worse outcomes (3). Our hospital is located at the Northwest of Spain and in the last months we noticed a never seen number of infections in cancer population. The aim of this study is to evaluate the severity of COVID19 and its impact on chemotherapy and surgery delay in pts undergoing neoadjuvant chemotherapy breast cancer. METHOD(S): We conducted a ambispective, unicenter, observational study of breast cancer pts, treated with neoadjuvant chemotherapy, between March 2020 and May 2022 at University Hospital A Coruna (Spain). We analyzed type of infection, need of hospitalization, chemotherapy and surgical delay, and its association with tumor type;BRCA germline mutation;clinical stage;treatment;vaccination status;and neutrophils, lymphocytes, and NLR before COVID-19 disease. RESULT(S): During the study period, from 1 March 2020 to 31 May 2022, 183 pts underwent neoadjuvant chemotherapy. A total of 23 (12.5%) pts experienced COVID-19 infection, of which 21 were diagnosed between January and May 2022. The median age was 47,91 years [range 33 - 69 years]. Luminal B HER 2 negative comprised the most common molecular subtype (40.9%), followed by Triple Negative (36.4%), Luminal B HER 2 positive (13.6%), and HER 2 enriched (9.1%). Germline mutations in BRCA account for 13.6% pts. At diagnosis, 4.5%, 72.7%, and 22.7% had stages I, II, and III respectively. Chemotherapy treatments included: paclitaxel followed by AdryamicineCyclophosphamide (AC) (45.4%);carboplatin - paclitaxel - trastuzumab - pertuzumab (18,2%);carboplatin - paclitaxel followed by AC (18,2%);KEYNOTE-756: pembrolizumab/placebo - paclitaxel followed by AC (13.7%);and paclitaxel - trastuzumab - pertuzumab followed by myocet - cyclophosphamide - trastuzumab - pertuzumab (4.5%). The association of G-CSF ocurred in 9 pts (40.9%). 22 pts were fully vaccinated, 8 pts (36.4%) with two doses and 13 pts (59.1%) with three doses. 77.3% pts experienced mild respiratory symptoms with 9.1% hospitalizations. The median duration of delays was 15 days for chemotherapy and 29,58 days for surgery. NLR percentil 25 was associated with COVID-19 type of infection. For those pts with a lower rate, infection was asymptomatic and for those with a higher rate symptoms were moderate (X2= 5,119, p = 0,024). CONCLUSION(S): COVID-19 disease become a high prevalent infection in pts undergoing neoadjuvant breast cancer chemotherapy. Most pts are fully vaccinated and experienced an indolent infection. NLR is an easily measurable and cost-effective parameter that could be useful as a prognostic marker of severity in COVID-19. We will continue to follow-up these pts to see the impact of chemotherapy or surgery delay in pathological complete response and disease-free survival until the congress in December 2022.
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We present a patient who was previously diagnosed with HIV and had multiple violaceous skin lesions at the time of his diagnosis. Following the initiation of antiretroviral therapy (ART), the number of lesions increased significantly and he developed shortness of breath, which prompted hospital admission for further workup. Biopsy of the skin lesions confirmed the diagnosis of Kaposi sarcoma (KS). Bronchoscopy with biopsy revealed KS lesions in his respiratory system. Imaging and biopsy confirmed KS invasion of lymph nodes. Due to widespread KS, he was diagnosed with immune reconstitution inflammatory syndrome (IRIS). Because of the lack of improvement on ART alone, he was started on chemotherapy, which decreased the size of existing skin lesions, stalled the development of new skin lesions, and led to symptom improvement. As a result of this case, we recommend that treatment teams have close follow-ups of patients started on ART and that they remain mindful of the possibility of IRIS. Disseminated KS may warrant a prompt response with chemotherapy to improve outcomes.
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Heart failure (HF) is a clinical syndrome with a wide spectrum of presentations and an even wider array of etiologies. Anthracyclines such as Doxorubicin, Daunorubicin, Idarubicin, and Epirubicin have demonstrated increased risk of HF with significant morbidity and mortality. We present an interesting case report of a patient with a history of breast cancer treated with Doxorubicin who presented with symptoms of HF who had a comprehensive evaluation that excluded the most common etiologies, narrowing our diagnosis to late onset doxorubicin induced HF with on-going recovery after initiation of guideline-directed medical therapy.
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET- CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.
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Introducao: A Purpura Trombocitopenica Imune (PTI), condicao caracterizada por contagem de plaquetas inferior a 100.000 muL e ausencia de anemia e neutropenia, afeta, principalmente, mulheres entre 15 e 50 anos. Corresponde a destruicao de plaquetas por auto anticorpos, podendo ser de origem idiopatica ou secundaria a infeccoes virais (como HIV / HBV / CMV);doencas linfoproliferativas (linfomas e leucemia linfocitica cronica);doencas reumaticas (como lupus eritematoso sistemico);e ate mesmo apos aplicacao de vacinas (como a da hepatite B;varicela;HPV;e da COVID-19). Os pacientes acometidos, geralmente, apresentam sintomas insidiosos e tipicos de doencas hemostaticas primarias como epistaxe, sangramento gengival, menorragia nas mulheres, purpuras e equimoses;a ocorrencia de hemorragia intracraniana e rara, porem quando presente, denota alta gravidade. O diagnostico e firmado apos todas as causas possiveis de plaquetopenia terem sido excluidas. O tratamento e preconizado para individuos sintomaticos ou com uma contagem plaquetaria inferior a 20.000 mm3, sendo a prednisona, 0,5 a 2 mg/kg/dia, farmaco de primeira escolha;como alternativas terapeuticas ha a imunoglobulina humana, esplenectomia, rituximabe e agonistas de trombopoetina. Objetivo: Relatar caso de PTI em paciente com Linfoma Nao Hodgkin (LNH) difuso de grandes celulas apos a vacinacao contra a COVID-19, com a ChAdOx1 nCov-19 (AstraZeneca). Descricao do caso: M.M.F., 35 anos, masculino, diagnosticado em dezembro de 2012 com LNH difuso de grandes celulas B, apos apresentar clinica de linfonodomegalia, dor lombar, paraparesia, perda ponderal e sudorese noturna;sendo o quadro confirmado atraves de biopsia de linfonodo cervical a esquerda, a qual indicou um linfoma de celulas B rico em celulas T e histiocitos com KI 67 de 90%. A biopsia de medula ossea mostrou hipercelularidade as custas de celulas de aspecto linfoide. O PETCT demonstrou linfonodos supraclaviculares a esquerda com SUV de 28,1;baco com SUV de 13,8;e multiplas lesoes osseas em coluna toracica, sacral e osso iliaco;as lesoes a nivel toracico comprimiam canal medular de T10 e T11. Em janeiro de 2013, iniciou tratamento com R-CHOP, sendo estabelecido, para este caso, 8 ciclos, em virtude da extensao da doenca. Em abril do mesmo ano, evoluiu com TVP femoropoplitea e infiltracao testicular, sendo tratado com warfarina e Radioterapia, respectivamente. Ultimo ciclo de RCHOP em julho de 2013, estando em remissao completa ate o presente momento. Em agosto de 2021, apresentou sangramento gengival, epistaxe, petequias e equimoses, dois meses apos ter se vacinado com a ChAdOx1 nCov-19. Exames iniciais: Hb 15,4 g/dL, leucocitos: 7.300 muL com diferencial normal e plaquetas: 2.000 muL. Internado para realizacao de pulsoterapia com prednisona 1 mg/kg/dia em associacao com azatioprina. Apresentou, apos 2 meses, plaquetas de 130.000 muL, e PET sem sinais de recidiva do LNH. Em novembro, apos a segunda dose da vacina, progrediu com mesma sintomatologia e com plaquetas de 27.000 muL;foi submetido a mesma terapeutica anterior, evoluindo com melhora. Conclusao: O presente relato alerta para a possibilidade de PTI secundaria a vacinacao contra a COVID-19 e a necessaria investigacao de uma possivel recidiva do LNH como causa da PTI (proliferacao linfoide b), ou seja, diferenciar uma recidiva da doenca de um efeito colateral da vacina. Copyright © 2022
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Introducao: O linfoma da celula do manto (LCM) e uma doenca rara e agressiva com poucas alternativas terapeuticas. Mas com a introducao de inibidores de tirosina kinase de Bruton tem mudado a sobrevida a longo prazo. Objetivo: descricao de um caso clinico em portadora da doenca com insuficiencia renal cronica. Material e metodos: Descricao do caso clinico: Paciente feminina, 65 anos de idade, queixa de cansaco, dor abdominal, hepatoesplenomegalia, presenca de linfonodomegalias, emagrecimento de 5 kg em 6 meses, sudorese noturna, Hb = 8.8 g/dL, plaquetopenia de 118.000/mm3, albumina = 2.5 g/dL. Antecedente de HAS e DPOC. Diagnostico de Linfoma de celulas do manto em maio de 2021 por biopsia de adenomegalia inguinal. Tratamento instituido foi R-CHOP e RDHAP em meses alternados, porem apos o segundo ciclo evoluiu com edema agudo de pulmao volumoso, insuficiencia renal com necessidade dialitica diaria (IRA- KDIGO III multifatorial), intubacao orotraqueal e tratamento em unidade intensiva por quadro de choque septico (KPC). Realizou terceiro ciclo de QT com RCHOP, mas com a piora clinica foi aventada hipotese de cuidados paliativos. Mas com a melhora recebeu mais 3 tratamentos com rituximabe mensal, persistiu com falencia renal e necessidade de hemodialise. Recebeu alta hospitalar e introduzido ibrutinibe 560 mg ao dia em 09/11/2021 sem muitos efeitos adversos. Resultados: PETScan do diagnostico 26/05/2021 mostra linfonodos axilares, volumosa esplenomegalia, linfonodos mediastinais, retroperitoneais e inguinais, area focal de intensa concentracao na transicao retossigmoide e na pelve (SUVmax:12.5), moderado derrame pleural bilateral. PETScan antes da introducao do ibrutinibe 10/11/202: reducao do metabolismo dos linfonodos axilares bilaterais, das dimensoes do baco, mas persistencia da area focal na transicao do retossigmoide (SUVmax:10.15). 6 meses apos o tratamento: 23/06/2022, nao se observam areas focais de atividade metabolica glicolitica anomala (Score 1 de Deauville), persiste com esplenomeagalia homogenea. A paciente segue em tratamento, no momento com ibrutinibe e em hemodialise de segunda a sexta. Apresentou infeccao pelo coronavirus em janeiro de 2022 sem sequelas. Atualmente clinicamente assintomatica, ECOG=0 e exames laboratoriais normais exceto pelo aumento de ureia e creatinina. Discussao: A causa da insuficiencia renal desenvolvida durante a internacao pode ser explicada por varios fatores como a sindrome de lise tumoral, uso da medicamento cisplatina, historia de HAS previa e ao quadro septico. A paciente evoluiu com regressao do quadro de esplenomegalia, adenomegalias e da massa em retrossigmoide ao longo dos 6 primeiros meses e atualmente se encontra sem evidencia de doenca em uso de ibrutinibe ha 10 meses. A dose da medicacao nao foi ajustada em vigencia de realizacao de hemodialise se acreditando que a droga apresenta depuracao renal minima. Ha poucos casos descritos na literatura do uso de ibrutinibe em pacientes com insuficiencia renal grave com clearance < 30 mL/minuto avaliando a seguranca e eficacia de tratamento. Conclusao: Tratamento em paciente portador de Linfoma de celulas do manto com insuficiencia renal grave pode ser tratado com ibrutinibe. Em nosso caso houve sucesso terapeutico, mas e imprescindivel acompanhar a resposta pois o tratamento e continuo ate a progressao da doenca ou eventos adversos graves. Copyright © 2022
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Introducao: Linfoma de celulas do manto (MCL) e uma doenca rara, mais frequente em homens, com idade media ao diagnostico de 68 anos. A terapia para MCL nao e curativa e praticamente todos os pacientes terao doenca refrataria ou recorrente. Quimioimunoterapia e a principal modalidade de tratamento de 1 linha, combinada a consolidacao com transplante autologo de medula ossea nos pacientes elegiveis. Mais recentemente, com a incorporacao de novas drogas na pratica clinica, ha mais opcoes de tratamento a partir da 2 linha, como os inibidores de tirosina quinase de Bruton (iBTK) e inibidor de bcl-2. Objetivos: Relatar um caso de paciente com MCL R/R, com historico de transplante renal e uso de imunossupressores, tratado com acalabrutinib com necessidade de ajuste de dose. Relato de caso: RCM, masculino, 70 anos, coronariopata, transplantado renal de doador cadaver em janeiro de 2018 devido a doenca renal cronica dialitica por sindrome hemolitico-uremica atipica em 2014, em uso de tacrolimus, micofenolato de mofetila e prednisona. Poucos meses apos o transplante apresentou linfocitose (14.900) e esplenomegalia, sem sintomas B. Biopsia de medula ossea mostrou infiltracao por MCL, positivo para CD20, BCL-2 e ciclina-D1. Na ocasiao, o paciente encontrava-se assintomatico e a doenca foi caracterizada como MCL leucemizado e indolente, foi optado por acompanhamento ambulatorial. Apos dois anos, apresenta linfocitose progressiva, aumento da esplenomegalia e trombocitopenia. Realizou tratamento com 6 ciclos de R-CHOP (ate 29/10/2020), atingindo resposta parcial. Apresentava 2,73% de linfocitos B monoclonais ao final do tratamento. Devido ao uso concomitante de imunossupressores para profilaxia de rejeicao do enxerto renal, durante a pandemia de COVID-19, optou-se por nao realizar manutencao com rituximabe. Apresentou recaida precoce, novamente com linfocitose progressiva e esplenomegalia 6 meses apos o termino do tratamento de 1 linha. Em junho de 2021 iniciou tratamento de 2 linha com iBTK de 2geracao - acalabrutinibe 200 mg/dia. Atingiu resposta hematologica com rapida normalizacao da linfocitose e resolucao da esplenomegalia, porem evoluiu com diarreia cronica, perda de peso e desnutricao, com prejuizo a qualidade de vida. Diante dos possiveis diagnosticos diferenciais - infeccao oportunista em paciente severamente imunossuprimido, infiltracao colonica por linfoma ou toxicidade medicamentosa, foi submetido a colonoscopia, com resultado normal, tornando toxicidade medicamentosa a principal hipotese. A dose do acalabrutinibe foi reduzida para 100 mg/dia em 20/04/22. Desde entao houve melhora da diarreia, o paciente voltou a ganhar peso e mantem resposta hematologica completa. Discussao e conclusao: Nao ha descricao de interacao entre acalabrutinib e inibidores de calcineurina, sirolimus e micofenolatomofetil. A posologia recomendada de acalabrutinibe e 100 mg de 12/12h, de forma universal. Pacientes transplantados em uso de imunossupressores nao foram incluidos nos estudos clinicos que levaram a aprovacao da droga para uso na pratica clinica. Esse caso ilustra que em cenarios especificos pode ser necessario realizar ajuste de dose para reduzir o risco de efeitos colaterais, sem prejuizo na eficacia do tratamento. Copyright © 2022
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BACKGROUND: Various anticancer drugs are effective therapeutic agents for cancer treatment; however, they cause severe toxicity in body organs. Cardiotoxicity is one of the most critical side effects of these drugs. Based on various findings, turmeric extract has positive effects on cardiac cells. OBJECTIVE: This study aims to evaluate how curcumin, as the main component of turmeric, may affect chemotherapy- induced cardiotoxicity. METHODS: A database search was performed up to April 2021 using "curcumin OR turmeric OR Curcuma longa" and "chemotherapy-induced cardiac disease", including their equivalents and similar terms. After screening the total articles obtained from the electronic databases, 25 relevant articles were included in this systematic review. RESULTS: The studies demonstrate lower body weight and increased mortality rates due to doxorubicin administration. Besides, cancer therapeutic agents induced various morphological and biochemical abnormalities compared to the non-treated groups. Based on most of the obtained results, curcumin at nontoxic doses can protect the cardiac cells mainly through modulating antioxidant capacity, regulation of cell death, and antiinflammatory effects. Nevertheless, according to a minority of findings, curcumin increases the susceptibility of the rat cardiomyoblast cell line (H9C2) to apoptosis triggered by doxorubicin. CONCLUSION: According to most nonclinical studies, curcumin could potentially have cardioprotective effects against chemotherapy-induced cardiotoxicity. However, based on limited, contradictory findings demonstrating the function of curcumin in potentiating doxorubicin-induced cardiotoxicity, well-designed studies are needed to evaluate the safety and effectiveness of treatment with new formulations of this compound during cancer therapy.
Subject(s)
Antineoplastic Agents , Curcumin , Animals , Apoptosis , Cardiotoxicity , Curcuma , Doxorubicin , RatsABSTRACT
Middle East respiratory syndrome coronavirus (MERS-CoV), belonging to the betacoronavirus genus can cause severe respiratory illnesses, accompanied by pneumonia, multiorgan failure, and ultimately death. CoVs have the ability to transgress species barriers and spread swiftly into new host species, with human-to-human transmission causing epidemic diseases. Despite the severe public health threat of MERS-CoV, there are currently no vaccines or drugs available for its treatment. MERS-CoV papain-like protease (PLpro) is a key enzyme that plays an important role in its replication. In the present study, we evaluated the inhibitory activities of doxorubicin (DOX) against the recombinant MERS-CoV PLpro by employing protease inhibition assays. Hydrolysis of fluorogenic peptide from the Z-RLRGG-AMC-peptide bond in the presence of DOX showed an IC50 value of 1.67 µM at 30 min. Subsequently, we confirmed the interaction between DOX and MERS-CoV PLpro by thermal shift assay (TSA), and DOX increased ΔTm by ~20 °C, clearly indicating a coherent interaction between the MERS-CoV PL protease and DOX. The binding site of DOX on MERS-CoV PLpro was assessed using docking techniques and molecular dynamic (MD) simulations. DOX bound to the thumb region of the catalytic domain of the MERS-CoV PLpro. MD simulation results showed flexible BL2 loops, as well as other potential residues, such as R231, R233, and G276 of MERS-CoV PLpro. Development of drug repurposing is a remarkable opportunity to quickly examine the efficacy of different aspects of treating various diseases. Protease inhibitors have been found to be effective against MERS-CoV to date, and numerous candidates are currently undergoing clinical trials to prove this. Our effort follows a in similar direction.
Subject(s)
Middle East Respiratory Syndrome Coronavirus , Humans , Middle East Respiratory Syndrome Coronavirus/metabolism , Papain/chemistry , Peptide Hydrolases/metabolism , Drug Repositioning , Doxorubicin/pharmacology , Doxorubicin/metabolismABSTRACT
SESSION TITLE: Pulmonary Issues in Transplantation Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after transplantation. While there is evidence that hematologic malignancy is associated with increased severity in COVID-19 infection, there is little description of PTLD and COVID-19. CASE PRESENTATION: A 68-year-old man and a 68-year-old female, both of whom had prior renal transplantation, were admitted to the hospital with COVID-19 pneumonia. Both patients were vaccinated against COVID-19, though were negative for spike protein antibodies. The man was treated with remdesivir and the woman was treated with remdesivir and dexamethasone. Both patients improved and were discharged. Within a month, both had recurrent symptoms of dyspnea and fever requiring re-admission. They were hypoxic, the man requiring high flow nasal cannula and the woman requiring nasal cannula to maintain SpO2>90%. They had positive COVID-19 PCR tests, with cycle threshold lower than in their initial admissions, as well as chest imaging with bilateral infiltrates. The man had a pleural effusion with cytology consistent with PTLD and perinephric mass and retroperitoneal lymphadenopathy with biopsy confirming PTLD. The woman had a renal sinus mass with biopsy confirming PTLD. Both patients were treated with another 5 days of remdesivir and started on dexamethasone. The medical team discussed monoclonal antibody treatment, but the patients did not meet EUA criteria and compassionate use request was denied. To treat PTLD, both were initiated on Rituximab, Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP). Since then, both patients have had complicated and prolonged hospital courses. The woman developed renal failure and severe C.diff colitis complicated by toxic megacolon requiring total colectomy. The man developed renal failure, CMV viremia, and pseudomonas UTI. The patients were able to be weaned to room air, though ultimately the woman had to be intubated due to poor mental status and remains on low oxygen settings. Both patients continue to be persistently positive for COVID-19 by PCR. DISCUSSION: This case illustrates diagnosis and treatment of PTLD in two patients with COVID-19 infection. Of particular interest was the use of Rituximab, an anti-CD-20 antibody which impairs humoral immunity, in the treatment of PTLD, as the drug has been associated with increased risk of severe COVID-19 infection. Rituximab was particularly concerning as both patients had persistent COVID-19 without development of immunity despite prior vaccination, and both continue to be positive despite two months of active infection. The patients had improvement of their respiratory status, though have had poor and complicated clinical courses with renal and infectious complications. CONCLUSIONS: Treatment of PTLD in patient's with active COVID-19 may impair ability to clear virus, though impact on outcomes is unclear. Reference #1: Simpson-Yap, S., de Brouwer, E., Kalincik, T., Rijke, N., Hillert, J. A., Walton, C., Edan, G., Moreau, Y., Spelman, T., Geys, L., Parciak, T., Gautrais, C., Lazovski, N., Pirmani, A., Ardeshirdavanai, A., Forsberg, L., Glaser, A., McBurney, R., Schmidt, H., … Peeters, L. (2021). Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis. Neurology, 97(19). https://doi.org/10.1212/WNL.0000000000012753 Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A… Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1). https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Passamonti, F., Cattaneo, C., Arcaini, L. Bruna, R., Cavo, M., Merli, F., Angelucci, E., Krampera, M., Cairoli, R., della Porta, M. G., Fracchiolla, N., Ladetto, M., Gambacorti Passerini, C., Salvini, M., Marchetti, M., Lemoli, R., Molteni, A., Busca, A., Cuneo, A., … Corradini, P. (2020). Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. The Lancet Haematology, 7(10). https://doi.org/10.1016/S2352-3026(20)30251-9 DISCLOSURES: No relevant relationships by Ian Mahoney No relevant relationships by Caroline Motschwiller
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SESSION TITLE: Variety in Risk Factors and Treatment of VTE SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Pulmonary embolism is a very common clinical entity that health care providers face routinely. Recurrent pulmonary embolism while on anti-coagulation therapy happens in about 2 to 4% of patients, but failure of multiple modalities of anti-coagulation is unusual and should prompt a closer evaluation. In this case we present an unusual cause of anti-coagulation failure. CASE PRESENTATION: A 65-year-old male patient diagnosed in 2016 with colon cancer status post hemi-colectomy and followed with CT surveillance. In 2016 he was also diagnosed with pulmonary embolism which was deemed secondary to his malignancy;this was treated with anti-coagulation for a finite duration. On surveillance CT scan in 2019 a new pulmonary embolism was diagnosed, and he was started on Apixaban therapy. In December of 2020 he was diagnosed with COVID19 which was mild to moderate in severity. A CT chest that was done at the time showed progression of the pulmonary embolism, so he was switched to low molecular weight heparin (LMWH). He presented in March of 2021 with hemoptysis and chest pain and another CT scan showed the same left pulmonary artery filling defect despite being on therapeutic LMWH. At this point we suspected an endovascular pathology, and a PET/CT scan was preformed which demonstrated an FGD positive left pulmonary artery endovascular lesion concerning for malignancy. Bronchoscopy and EBUS was done by interventional pulmonary team and biopsies from the left PA artery were taken. Pathology came back highly suspicious for angiosarcoma. The patient received chemotherapy (AIM;Adriamycin, Ifosfamide with MESNA) with an excellent response. DISCUSSION: Pulmonary artery sarcoma is a rare tumor that usually originates from the intimal layer of the pulmonary artery. It can mimic pulmonary embolism in clinical presentation and on imaging studies. In an observational analysis study published in Journal of Thoracic Disease;nearly half of 391 confirmed cases were originally misdiagnosed as pulmonary embolism. The treatment of pulmonary artery sarcoma is typically surgical intervention, although some patients may benefit from the use of chemotherapy. CONCLUSIONS: Pulmonary embolism is by far the most common cause of pulmonary artery filling defect on CT scan, typically treated with anti-coagulation with good outcomes. In the setting of therapy failure other etiologies must be considered. Although difficult to distinguish from PE, knowing the distinguishing clinical and radiologic will aid an accurate diagnosis. Reference #1: Symptoms, Diagnosis, and Therapy of Primary Sarcomas of the Pulmonary Artery. By I. Kruger, A. Borowski, M. Horst, E.R. de Vivie, W. Gross-Fengels. Thorac Cardiovasc Surg. 1990 Apr;38(2):91-5. doi: 10.1055/s-2007-1014001 Reference #2: Primary pulmonary artery sarcoma: a close associate of pulmonary embolism, 20-year observational analysis. Debabrata Bandyopadhyay, 1 Tanmay S. Panchabhai,2 Navkaranbir S. Bajaj,3 Pradnya D. Patil,4 and Matthew C. Bunte5 J Thorac Dis, v.8(9);2016 Sep, PMC5059338 doi: 10.21037/jtd.2016.08.89 Reference #3: Al-Mehisen, Rabah et al. "Primary pulmonary artery sarcoma: A rare and overlooked differential diagnosis of pulmonary embolism. Clues to diagnosis." International journal of surgery case reports vol. 65 (2019): 15-19. doi:10.1016/j.ijscr.2019.10.014 DISCLOSURES: No relevant relationships by Ahmad Allaham No relevant relationships by Mark Peicher