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Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.
Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.
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Anticorpos Monoclonais , Mieloma Múltiplo , Adolescente , Adulto , Humanos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Estudos Prospectivos , Resultado do TratamentoRESUMO
How to cite this article: Arunachala S, Kumar J. mNUTRIC Score in ICU Mortality Prediction: An Emerging Frontier or Yet Another Transient Trend? Indian J Crit Care Med 2024;28(5):422-423.
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Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. However, there is a lack of comprehensive data from low- and middle-income countries (LMICs) regarding factors influencing COPD outcomes, particularly in regions where biomass exposure is prevalent. Objective: The Factors Affecting Survival in Severe and Very Severe COPD Patients Admitted to Tertiary Centers of India (FAST) study aims to address this gap by evaluating factors impacting survival and exacerbation rates among COPD patients in LMICs like India, with a specific focus on biomass exposure, clinical phenotypes, and nutritional status in patients admitted to the Intensive Care Unit (ICU). Methods: The FAST study is an observational cohort study conducted in university teaching hospitals across India. The study aims to enroll 1000 COPD patients admitted to the ICU meeting specific inclusion criteria, with follow-up assessments conducted every 6 months over a 2-year period. Data collection includes demographic information, clinical manifestations, laboratory investigations, pulmonary function tests, medications, nutritional status, mental health, and health-related quality of life. Adjudication of exacerbations and mortality will also be undertaken. The FAST study seeks to provide crucial insights into COPD outcomes in LMICs, informing more precise management strategies and mitigating the burden of COPD in these settings. By evaluating factors such as biomass exposure, clinical phenotypes, and nutritional status, the study aims to address key knowledge gaps in COPD research. How to cite this article: Arunachala S, Devapal S, Swamy DSN, Greeshma MV, Ul Hussain I, Siddaiah JB, et al. Factors Affecting Survival in Severe and Very Severe COPD after Admission in ICUs of Tertiary Care Centers of India (FAST COPD): Study Protocol for a Multicentric Cohort Study. Indian J Crit Care Med 2024;28(6):552-560.
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BACKGROUND: Infections by multidrug-resistant organisms (MDRO) are a major hurdle in hematopoietic stem-cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in-turn leads to transmigration of gut bacteria and sepsis. Pre-transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre-transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. METHODS: A single-center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre-transplant stool/throat surveillance cultures, and their impact on overall 100-day and post-100-day to 6-month post-transplant survival were analyzed. RESULTS: Sixty-four patients were included in the study. Pre-transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase-producing genes (mainly New Delhi metallo-beta-lactamase-1 [NDM-1] and oxacillinase-48 [OXA-48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri-engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All-cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post-HSCT, respectively. The 100-day and post-100-day all-cause mortality rates were higher in patients with Gram-negative MDRO bloodstream infections (p < .012 and <.008, respectively). CONCLUSION: MDRO infections can adversely affect HSCT outcomes. Pre-transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes.
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Transplante de Células-Tronco Hematopoéticas , Neoplasias , Sepse , Humanos , Farmacorresistência Bacteriana Múltipla , Estudos Retrospectivos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sepse/tratamento farmacológicoRESUMO
To discover the best-in-class Bruton's Tyrosine Kinase (BTK) inhibitors, for th treatment of autoimmune disorders like cancer (B-Cell Lymphoma (BCL)) and rheumatoid arthritis (RA), in the present investigation, novel structural optimizations were carried out. Introduction of novel bicyclic amine linkers and aromatic backbone led to series of compounds 9a-h and 14a-u. Compound 14b was found to be potent, orally bioavailable, selective and irreversible BTK inhibitor. In vitro, 14b showed IC50 of 1.0 nM and 0.8 nM, in BTK and TMD8 assays, respectively. In vivo,14b displayed robust efficacy in collagen-induced arthritis (CIA) and TMD8 xenograft models, which could be correlated with its improved oral bioavailability. In the repeated dose acute toxicity study, 14b showed no adverse changes, indicating that the BTK inhibitor 14b could be viable therapeutic option for the treatment of autoimmune disorders.
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Artrite Experimental , Artrite Reumatoide , Animais , Humanos , Tirosina Quinase da Agamaglobulinemia , Inibidores de Proteínas Quinases/química , Aminas/farmacologia , Aminas/uso terapêutico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológicoRESUMO
Dysregulated JAK-STAT signaling has been proven to be involved in several immune-mediated diseases. Several janus kinase (JAK) inhibitors have been approved for the treatment of various inflammatory and autoimmune diseases such as rheumatoid arthritis (RA), plaque psoriasis, psoriatic arthritis, inflammatory bowel disease (IBD). Here, we report the design, optimisation, synthesis and biological evaluation of momelotinib analogues (a pyrimidine based JAK inhibitor), to get pan-JAK inhibitors. Systematic structure activity relationship studies led to the discovery of compound 32, which potently inhibited JAK1, JAK2 and JAK3. The in vivo investigation indicated that compound 32 possessed favourable pharmacokinetic properties and displayed superior anti-inflammatory efficacy than momelotinib 1. Accordingly, compound 32 was advanced into preclinical development.
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Doenças do Sistema Imunitário , Inibidores de Janus Quinases , Benzamidas , Humanos , Inibidores de Janus Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêuticoRESUMO
Background and Aims: Many patients with COVID-19 become critically ill and requireICU admission. Risk factors associated with mortality have been studied, but this study provides insight regarding disease progression and hence help to plan rescue strategies to improve patient outcome. Material and Methods: This retrospective, observational study included all patients with diagnosis of COVID-19 from March1 to June30,2021 who died in hospital. Results: During the study period, 1600 patients were admitted, with 1138 (71%) needing ICU care. There were 346 (21.6%) deaths, distributed as 15.8%(n = 55) within 48h of admission, 46.2%(n = 160) in next 10 days, and 37.8%(n = 131) thereafter. This trimodal mortality pattern of distribution was similar to polytrauma patients. Patients were divided into categories according to time duration from admission to death. In our cohort, 235 (14.7%) patients required mechanical ventilation, with a mortality of 85.4%(n = 201). Tachypnea was significantly (P < 0.001) associated with death at all times; however, hypotension was associated with early death and low oxygen saturation with poor outcome upto 10 days (P < 0.001). Refractory hypoxia was cause of death in all three groups, while other causes in group II were AKI (28%), sepsis (18%), and MODS (10%). Group III patients had different causes of mortality, including barotrauma (9%), pulmonary thromboembolism (8%), refractory hypercarbia (12%), MODS (13%), AKI (10%), sepsis (7%), and cardiac events (6%). Conclusion: While physiological dearrangements are associated with rapid progression and early death, complications related to hyper-coagulable state, lung injury, and organ failure lead to death later. Providing quality care to a high volume of patients is a challenge for all, but posthoc analysis such as air crash investigation can help find out potential areas of improvement and contribute to better outcomes and mortality reduction.
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BACKGROUND: Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. METHODS: This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. FINDINGS: Of 457 patients screened for eligibility, 402 were randomly allocated-195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group-and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2-19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4-19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11-10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53-0·93], p=0·0075). The most frequent grade 3-4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32-0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. INTERPRETATION: A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. FUNDING: Karyopharm Therapeutics.
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Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Hidrazinas/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Triazóis/administração & dosagem , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Hidrazinas/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Triazóis/efeitos adversosRESUMO
The ever-growing prevalence of Type-2 diabetes in the world has an urgent need for multiple orally effective agents that can regulate glucose homeostasis. G-Protein coupled receptor 119 (GPR 119) agonists have demonstrated the glucose-dependent insulin secretion and showed beneficial effects on glycemic control in humans and/or relevant animal models. Herein, we describe our efforts towards identification of a potent and oral GPR 119 agonist 13c (ZY-G19), which showed in vitro potency in the cell-based assay and in vivo efficacy without exerting any significant signs of toxicity in relevant animal models.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Receptores Acoplados a Proteínas G/agonistas , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-AtividadeRESUMO
Selective inhibition of janus kinase (JAK) has been identified as an important strategy for the treatment of autoimmune disorders. Optimization at the C2 and C4-positions of pyrimidine ring of Cerdulatinib led to the discovery of a potent and orally bioavailable 2,4-diaminopyrimidine-5-carboxamide based JAK3 selective inhibitor (11i). A cellular selectivity study further confirmed that 11i preferentially inhibits JAK3 over JAK1, in JAK/STAT signaling pathway. Compound 11i showed good anti-arthritic activity, which could be correlated with its improved oral bioavailability. In the repeat dose acute toxicity study, 11i showed no adverse changes related to gross pathology and clinical signs, indicating that the new class JAK3 selective inhibitor could be viable therapeutic option for the treatment of rheumatoid arthritis.
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Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Descoberta de Drogas , Janus Quinase 3/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Animais , Antirreumáticos/síntese química , Antirreumáticos/química , Artrite Experimental/sangue , Linhagem Celular , Relação Dose-Resposta a Droga , Humanos , Janus Quinase 3/sangue , Janus Quinase 3/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Relação Estrutura-AtividadeRESUMO
As in many other countries, the field of genetic counseling is in its initial stages of development in India, where there are efforts to streamline the profession and to implement graduate-level training programs. We implemented an elective course on genetic counseling at the undergraduate level in a private university in India to assess students' interest, to provide early exposure for students interested in pursuing the career, and to aid recruitment. To assess satisfaction with the course and recruitment outcomes, we sent a course evaluation survey to 332 students and received 134 responses. Familiarity with genetic counseling topics increased significantly after completing the course. Of the 42 respondents who reported they were planning to pursue formal genetic counseling training, 21% (n = 9/42) became interested in the profession as a result of taking this course. Survey respondents who were prospective applicants to genetic counseling training programs referred mostly to the websites of the National Society of Genetic Counselors and the American Board of Genetic Counseling for information on genetic counseling and training. Barriers to entry into the field included lack of shadowing opportunities, inadequate coursework, and limited opportunities to interact with practicing genetic counselors. Respondents stated that additional case studies as well as observation of patient interactions would elucidate the role of a genetic counselor and help define the scope of the practice in India and other countries. Overall, genetic counseling education at the undergraduate level is a scalable way to improve understanding of genetic counseling topics, increase professional interest in the field, and support workforce development.
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Conselheiros/psicologia , Aconselhamento Genético/psicologia , Estudantes/psicologia , Recursos Humanos , Educação de Pós-Graduação , Humanos , Estudos Prospectivos , Desenvolvimento de Pessoal , Inquéritos e Questionários , UniversidadesRESUMO
PI3Kδ is implicated in various inflammatory and autoimmune diseases. For the effective treatment of chronic immunological disorders such as rheumatoid arthritis, it is essential to develop isoform selective PI3Kδ inhibitors. Structure guided optimization of an imidazo-quinolinones based pan-PI3K/m-TOR inhibitor (Dactolisib) led to the discovery of a potent and orally bioavailable PI3Kδ isoform selective inhibitor (10h), with an improved efficacy in the animal models.
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Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Descoberta de Drogas , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Quinolonas/farmacologia , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Inibidores de Fosfoinositídeo-3 Quinase/síntese química , Inibidores de Fosfoinositídeo-3 Quinase/química , Quinolonas/síntese química , Quinolonas/química , Relação Estrutura-AtividadeRESUMO
TGR5 is a member of G protein-coupled receptor (GPCR) superfamily, a promising molecular target for metabolic diseases. Activation of TGR5 promotes secretion of glucagon-like peptide-1 (GLP-1), which activates insulin secretion. A series of 2-thio-imidazole derivatives have been identified as novel, potent and orally efficacious TGR5 agonists. Compound 4d, a novel TGR5 agonist, in combination with Sitagliptin, a DPP-4 inhibitor, has demonstrated an adequate GLP-1 secretion and glucose lowering effect in animal models, suggesting a potential clinical option in treatment of type-2 diabetes.
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Hipoglicemiantes/química , Imidazóis/química , Receptores Acoplados a Proteínas G/agonistas , Animais , Sítios de Ligação , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/veterinária , Quimioterapia Combinada , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Meia-Vida , Humanos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Imidazóis/farmacocinética , Imidazóis/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Receptores Acoplados a Proteínas G/metabolismo , Fosfato de Sitagliptina/uso terapêutico , Relação Estrutura-AtividadeRESUMO
BACKGROUND: A previous retrospective analysis of our cardiac surgery patients showed shortened ventilation time and hospital stay among patients receiving rigid sternal fixation compared to sternal wire fixation. We performed a prospective randomized study to further investigate these outcomes and determine if rigid closure can provide reduced pain after cardiac surgery. METHODS: Patients undergoing cardiac surgery between July 2011 and May 2014 were prospectively randomized into wire closure (Group C) or rigid fixation using sternal plates (Group R) groups. Age above 80, emergency surgery, redo sternotomy, and immunosuppression were among major exclusion criteria precluding randomization. Intubation time was recorded for all patients. Pain scores were determined daily from postoperative day 1 until day 5 at 6 a.m. using a numeric rating scale. Narcotic pain medication requirements from day 1 to 5 were collected and converted into intravenous morphine equivalents. RESULTS: Of 80 patients, 39 patients were in Group R (average age 65 ± 8; 31 male and 8 female) and 41 patients were in Group C (average age 66 ± 9; 34 male and 7 female). Group R patients had a higher body mass index than patients in Group C (Group R: 31 ± 5; Group C: 29 ± 5; P = .04). No significant differences in the end points of intubation time and postoperative pain were observed. Conclusion: This randomized study of cardiac surgery patients showed no significant benefits of rigid fixation over conventional sternal wire closure with regard to intubation time, postoperative pain, or length of hospital stay.
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Placas Ósseas , Fios Ortopédicos , Cardiopatias/cirurgia , Esternotomia/métodos , Esterno/cirurgia , Deiscência da Ferida Operatória/prevenção & controle , Idoso , Procedimentos Cirúrgicos Cardíacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND & OBJECTIVES: Subtelomeres are prone to deleterious rearrangements owing to their proximity to unique sequences on the one end and telomeric repetitive sequences, which increase their tendency to recombine, on the other end. These subtelomeric rearrangements resulting in segmental aneusomy are reported to contribute to the aetiology of idiopathic intellectual disability/developmental delay (ID/DD). We undertook this study to estimate the frequency of subtelomeric rearrangements in children with ID/DD. METHODS: One hundred and twenty seven children with idiopathic ID/DD were tested for subtelomeric rearrangements using karyotyping and FISH. Blood samples were cultured, harvested, fixed and GTG-banded using the standard protocols. RESULTS: Rearrangements involving the subtelomeres were observed in 7.8 per cent of the tested samples. Detection of rearrangements visible at the resolution of the karyotype constituted 2.3 per cent, while those rearrangements detected only with FISH constituted 5.5 per cent. Five deletions and five unbalanced translocations were detected. Analysis of parental samples wherever possible was informative regarding the inheritance of the rearrangement. INTERPRETATION & CONCLUSIONS: The frequency of subtelomeric rearrangements observed in this study was within the reported range of 0-35 per cent. All abnormal genotypes were clinically correlated. Further analysis with array technologies presents a future prospect. Our results suggest the need to test individuals with ID/DD for subtelomeric rearrangements using sensitive methods such as FISH.
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Deficiências do Desenvolvimento/genética , Rearranjo Gênico/genética , Deficiência Intelectual/genética , Telômero/genética , Adolescente , Criança , Pré-Escolar , Aberrações Cromossômicas , Deficiências do Desenvolvimento/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Lactente , Deficiência Intelectual/patologia , Cariótipo , MasculinoRESUMO
Melphalan-induced encephalopathy is a rare complication observed in patients undergoing autologous stem cell transplantation (ASCT) and is characterized by symptoms ranging from drowsiness to seizures. Previous reports have described similar cases, including a review of a large cohort of patients in whom melphalan-associated encephalopathy was identified in 2% of the patients undergoing ASCT. We describe the case of a 63-year-old male with Multiple Myeloma and underlying chronic kidney disease (CKD) who underwent ASCT with a reduced dose of melphalan due to renal dysfunction in complete remission following induction therapy and subsequent neurological deterioration, which necessitated an extensive evaluation of several neurological and infective etiologies. In this report, we highlight that melphalan-associated encephalopathy is a distinct entity complicating ASCT in patients with myeloma, especially in those with preexisting renal insufficiency, and consider its management.
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ABSTRACT: Using one's own immune system for curing cancer has been an active field of research in cancer biology and therapeutics. One such opportunity in cellular immunotherapy is adoptive cell transfers. With the recent approval of CAR-T therapy as a cancer treatment, a whole new paradigm of cancer treatment has opened-up, with a ray of hope for relapsed/refractory cancer patients. Despite promising clinical outcomes, the therapy is in its early phase and remains out of reach for most patients due to its high cost and logistic challenges. In India, these therapies are unavailable and further confounded by the economic challenges and a large population. In this review, we discuss various aspects of T-cell immunotherapies with a special focus on CAR-T in the Indian scenario. We touch upon the basic scientific aspects, mechanism of action, manufacturing, clinical aspects and commercial aspects of the CAR-Tcell therapies and its future worldwide and in India.
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INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study cohort was International Scoring System (ISS)-III (55%), and IgG-kappa (44%) was the commonest subtype of multiple myeloma (MM). Light chain myeloma was found in 23.5% of patients. Pretransplant, 42%, 48%, and 10% patients were in more than very good partial response (>VGPR), very good partial response (VGPR), and partial response (PR), respectively. The median duration of follow-up was 57.2 months (range: 12.1-120.2 months). The entire cohort's 5-year overall survival (OS) and progression-free survival (PFS) were 89.1% and 41.8%, respectively. CONCLUSION: Bortezomib based triplet induction regimens were effective and well tolerated in this retrospective analysis of Indian patients. We observed that AHCT effectively achieves deep and durable remission in MM.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Bortezomib/uso terapêutico , Quimioterapia de Indução , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos RetrospectivosRESUMO
Cyclospora cayetanensis, a recently described coccidian parasite causes severe gastroenteric disease worldwide. Limited studies are found on the incidence of C. cayetanensis infection from India; hence remains largely unknown. To date, no case of cyclosporiasis from eastern India has been reported. In this study, we described an incidental case of C. cayetanensis in a 30 years old Bengali female patient with no travel history from eastern India. In June 2022, the patient presented with a history of diarrhoea persisting for more than two months with continuous passage foul smelling stools for which she took multiple antibiotics that were ineffective. There were no Salmonella, Shigella, or Vibrio-like organisms in the patient's faecal sample, and Toxin A/B of Clostridium difficile was also not detected by ELISA. The patient was HIV-negative. Finally, UV autofluorescence and DNA-based diagnosis confirmed the presence of C. cayetanensis, and the treatment with a combination of appropriate antibiotics was successful. This case report could raise awareness about C. cayetanensis associated diarrhoeal cases in India.