RESUMEN
PURPOSE: To develop and validate a multiplex conventional PCR assay to simultaneously detect Cryptosporidium spp., Entamoeba histolytica, and Giardia lamblia in diarrheal samples as a rapid, cost-effective, and sensitive diagnostic tool for prevalent co-infections for improved diagnostic accuracy and efficiency in resource-limited settings. METHODS: Stool samples collected from patients with gastrointestinal symptoms after taking written consent, processed via wet mount, iodine mount, and PCR assays. Cohen's kappa statistical analysis was done to test agreement. RESULT: Among 240 patients, 28.75% showed intestinal protozoa via Microscopy; Single-plex and multiplex PCR demonstrated 100% concordance, detecting 27.9%; confirmed by sequencing. Highest parasite positivity was observed in transplant and immunocompromised patients, with moderate to almost perfect agreement between microscopy and molecular methods. CONCLUSION: Multiplex-conventional PCR offers superior sensitivity and specificity over microscopy and 100% concordance with single-plex PCR, enabling rapid, cost-effective diagnosis of multiple parasites from single stool sample. Its adoption could revolutionize parasitic infection management in routine diagnostics.
Asunto(s)
Entamoeba histolytica , Heces , Giardia lamblia , Microscopía , Reacción en Cadena de la Polimerasa Multiplex , Sensibilidad y Especificidad , Humanos , Heces/parasitología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Microscopía/métodos , Giardia lamblia/genética , Giardia lamblia/aislamiento & purificación , Adulto , Entamoeba histolytica/genética , Entamoeba histolytica/aislamiento & purificación , Femenino , Masculino , Persona de Mediana Edad , Cryptosporidium/genética , Cryptosporidium/aislamiento & purificación , Niño , Adulto Joven , Preescolar , Parasitosis Intestinales/diagnóstico , Parasitosis Intestinales/parasitología , Adolescente , Benchmarking , Coinfección/parasitología , Coinfección/diagnóstico , Anciano , Diarrea/parasitología , Diarrea/diagnóstico , Giardiasis/diagnóstico , Giardiasis/parasitología , Técnicas de Diagnóstico Molecular/métodos , LactanteRESUMEN
Four novel KIR alleles KIR3DL1*0010120, KIR3DS1*01315, KIR3DL3*0020703 and KIR2DL4*0010310 identified using next-generation sequencing.
Asunto(s)
Alelos , Secuenciación de Nucleótidos de Alto Rendimiento , Receptores KIR , Donantes de Tejidos , Humanos , India , Receptores KIR/genética , Células Madre Hematopoyéticas/metabolismo , Trasplante de Células Madre Hematopoyéticas , Receptores KIR3DL1/genética , Exones , Prueba de Histocompatibilidad , Genotipo , Receptores KIR3DS1/genética , Receptores KIR2DL4/genéticaRESUMEN
This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009-2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p = .031) and brain leukostasis (p = .006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management.
RESUMEN
ABSTRACT: BCRâ·ABL1 translocation and JAK2V617F mutations are canonical variants of myeloproliferative neoplasms (MPNs). Traditionally considered mutually exclusive, they may rarely coexist. We report the clinicopathological profile and treatment outcomes of four MPN patients with coexistence of these disease-defining genetic variants. Both mutations were detected simultaneously in three patients who did not harbor tell-tale signs of CML and were evaluated for both BCRâ·ABL1 and JAK2V617F based on clues from hemogram, peripheral-blood and bone-marrow examination. All were treated with imatinib and hydroxyurea and attained major molecular response after 2-7 months. In another patient, JAK2V617F was detected 15 years after the diagnosis of CML at the time of evaluation of loss of hematological and molecular response. She was treated with dasatinib but no hematologic or molecular response was attained after 6 months despite good compliance. In conclusion, BCRâ·ABL1 and JAK2V617F may rarely coexist in MPN with variable temporal evolution, clinicopathological profile, and treatment response.
RESUMEN
BACKGROUND: Extramedullary blast proliferations (EBPs) are known to occur in around 15% of chronic myeloid leukemia (CML) patients in the blast phase. Immunophenotypically, the EBPs are commonly myeloid as compared to the lymphoid. Amongst the lymphoid EBPs, T-lymphoblastic type is considerably rare. Furthermore, the occurrence of EBPs at the initial clinical presentation is extremely rare and such presentations almost always portend the occurrence of an imminent hematological blast crisis shortly. CASE: A 25-year-old male presented with abdominal fullness for 1 month. There was no history of abdominal pain, vomiting, jaundice, weight loss, or night sweats. On clinical examination, the patient was found to have pallor and was febrile. There was hepatosplenomegaly and a single, firm, mobile, left posterior cervical lymph node measuring 1.5 × 1 cm was palpable. Routine blood counts revealed anemia, leukocytosis, and thrombocytopenia. A fine-needle aspiration (FNA) from the cervical revealed T-lymphoid EBP, confirmed by flow cytometry. Subsequently, his bone marrow examination revealed a diagnosis of CML with BCR::ABL1 fusion. Thus, a final diagnosis of CML with extramedullary T-lymphoid blast crisis localized to the cervical lymph node was rendered. CONCLUSIONS: The present report, besides highlighting the utility of FNA cytology in rendering such challenging diagnoses, also reiterates the significance of ancillary techniques, such as flow cytometry, which play a key role in early diagnosis and exact characterization of such rare and aggressive hematolymphoid neoplasms.
RESUMEN
BACKGROUND: Immune dysregulation is crucial in the pathogenesis of acquired aplastic anaemia (aAA). There is paucity of data regarding correlation of baseline cytokine profile with treatment response in aAA. OBJECTIVE: Present prospective case-control study aimed to correlate the baseline cytokines in patients with aAA with the treatment response. METHODS: Fifty-one patients with newly-diagnosed aAA > 13 years of either sex were enrolled over 1.5 years. Twenty age-and sex-matched healthy controls (HC) were also included. The cytokine profile (IL-2, 4, 6, 8, 10, 17, IFN-γ and TNF-α) in the peripheral blood plasma of aAA patients was performed at the baseline using cytometric bead analysis. The cytokine levels were compared with HC and correlated with response to immunosuppressive therapy (IST) at 3-months. RESULTS: The median age of cases was 29 years (range,13-74). The cases had higher mean levels of IL2 (p = 0.326), IL4 (p = 0.038), IL6 (p = 0.000), IL10 (p = 0.002), TNF-α (p = 0.302), IFN-γ (p = 0.569) and IL-17 (p = 0.284) than the HC. The baseline levels of all the cytokines were higher (statistically non-significant) among responders (n = 13) than the non-responders (n = 14) to IST. CONCLUSIONS: Baseline cytokine profile in patients with aAA might predict response to the IST. Larger studies are needed to validate our results.
Asunto(s)
Anemia Aplásica , Citocinas , Humanos , Anemia Aplásica/sangre , Anemia Aplásica/diagnóstico , Anemia Aplásica/tratamiento farmacológico , Anemia Aplásica/terapia , Masculino , Femenino , Adulto , Citocinas/sangre , Persona de Mediana Edad , Adolescente , Estudios de Casos y Controles , Adulto Joven , Anciano , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
Standard therapy for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL) involves salvage chemotherapy followed by autologous hematopoietic stem cell transplant. However, information regarding the number of patients receiving salvage therapy and associated factors is not available from low/middle income countries (LMICs). All patients treated at our center with RR DLBCL from 2016 to 2021 were included in the study. Univariate and multivariate analyses was performed to find factors associated with the lack of receipt of salvage chemotherapy. Eighty-five patients were included in the study. Most patients had primary refractory disease (69.4%). Only 26 patients received standard salvage therapy, while the others (N = 59) received metronomic/palliative oral therapy. On univariate analysis, patients with an annual income below India's Gross National Income per capita (p = 0.014), an education level below Class XII (p = 0.025), Stage III/IV disease at relapse (p = 0.018) and CNS relapse (p = 0.027) were more likely to receive palliative therapy. Conversely, patients with a late relapse were more likely to receive salvage therapy (p = 0.001). On multivariate analysis, patients with Stage III/IV relapse (p = 0.030) and an education level less than Class XII (p = 0.012) were more likely to receive palliative therapy, while patients with a late relapse (p = 0.001) were more likely to receive salvage therapy. Patients who received salvage therapy had a longer Median OS than those who received palliative therapy (p < 0.001). Timing of relapse, stage at relapse and educational status of the patient are significant factors affecting access to effective therapy for patients with RR DLBCL in LMICs.
RESUMEN
A single guanosine deletion/insertion (4G/5G) polymorphism in the promoter region of plasminogen activator inhibitor-1 (PAI-1) gene encoding PAI-1 protein has been investigated in deep vein thrombosis (DVT) patients. The association between PAI-1 4G/5G polymorphism and increased risk of DVT has been reported in some studies, while others have reported a lack of association. The present study aimed to investigate if the PAI-1 4G/5G polymorphism is associated with an increased risk of DVT in the Indian population and to assess its association with thrombophilic risk factors. Fifty-two adult patients with a history of chronic or recurrent DVT and 52 healthy adult controls were genotyped for PAI-1 4G/5G polymorphism. Plasma levels of PAI-1 and other thrombophilic risk factors were also measured. PAI-1 4G/5G polymorphism was not significantly associated with an increased risk of DVT. Protein C deficiency was significantly associated with the 4G/4G genotype. Patients with the 4G/4G genotype had significantly reduced PAI-1 levels as compared to the controls. PAI-1 4G/5G polymorphism did not significantly contribute to an increased risk of DVT in the Indian population. However, in the presence of thrombophilic risk factor abnormalities, the risk of DVT is increased in individuals with the 4G/4G genotype in the Indian cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01660-3.
RESUMEN
BACKGROUND: Mycobacterium w (Mw), an immunomodulator, resulted in better clinical status in severe coronavirus infectious disease 19 (COVID-19) but no survival benefit in a previous study. Herein, we investigate whether Mw could improve clinical outcomes and survival in COVID-19. MATERIALS AND METHODS: In a multicentric, randomized, double-blind, parallel-group, placebo-controlled trial, we randomized hospitalized subjects with severe COVID-19 to receive either 0.3 mL/day of Mw intradermally or a matching placebo for three consecutive days. The primary outcome was 28-day mortality. The co-primary outcome was the distribution of clinical status assessed on a seven-point ordinal scale ranging from discharged (category 1) to death (category 7) on study days 14, 21, and 28. The key secondary outcomes were the change in sequential organ failure assessment (SOFA) score on days 7 and 14 compared to the baseline, treatment-emergent adverse events, and others. RESULTS: We included 273 subjects (136 Mw, 137 placebo). The use of Mw did not improve 28-day survival (Mw vs. placebo, 18 [13.2%] vs. 12 [8.8%], P = 0.259) or the clinical status on days 14 (odds ratio [OR], 1.33; 95% confidence intervals [CI], 0.79-2.3), 21 (OR, 1.49; 95% CI, 0.83-2.7) or 28 (OR, 1.49; 95% CI, 0.79-2.8) between the two study arms. There was no difference in the delta SOFA score or other secondary outcomes between the two groups. We observed higher injection site reactions with Mw. CONCLUSION: Mw did not reduce 28-day mortality or improve clinical status on days 14, 21 and 28 compared to placebo in patients with severe COVID-19. [Trial identifier: CTRI/2020/04/024846].
RESUMEN
Extramedullary relapse in patients with multiple myeloma (MM) is often associated with loss of biochemical response and the appearance of measurable residual disease in the bone marrow. Fever is an unusual presenting manifestation of MM. Treatment of extramedullary relapse in patients progressing on proteasome inhibitors, anti-CD38 monoclonal antibodies and immunomodulatory drugs is challenging, as access to chimeric antigen receptor T-cells and bispecific antibodies is limited. We report a case of relapsed MM who presented with fever and hepatic space-occupying lesion mimicking hepatocellular carcinoma. In this case report, we also present our experience of using a novel combination regimen comprising Dara-Pom-Benda-Dexa (daratumumab, pomalidomide, dexamethasone and bendamustine) for relapsed MM.
Asunto(s)
Mieloma Múltiple , Talidomida/análogos & derivados , Humanos , Mieloma Múltiple/patología , Clorhidrato de Bendamustina/uso terapéutico , Dexametasona/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Hígado/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was â¹1,26,830 in the PGT arm compared to â¹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was â¹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of â¹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.
Asunto(s)
Anticoagulantes , Citocromo P-450 CYP2C9 , Economía Farmacéutica , Relación Normalizada Internacional , Vitamina K Epóxido Reductasas , Warfarina , Humanos , Warfarina/economía , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Citocromo P-450 CYP2C9/genética , Anciano , Vitamina K Epóxido Reductasas/genética , Anticoagulantes/administración & dosificación , Anticoagulantes/economía , Anticoagulantes/uso terapéutico , Pruebas de Farmacogenómica/economía , Adulto , Farmacogenética/economía , Análisis Costo-BeneficioRESUMEN
PURPOSE: Denosumab is clinically superior to zoledronic acid (ZA) for preventing and delaying time to first and subsequent skeletal-related events (SREs) among patients with breast cancer (BC) with bone metastases. We evaluated the cost and health benefits of denosumab and ZA (once every 4 weeks and once every 12 weeks) among four different molecular subtypes of BC with bone metastases in India. MATERIALS AND METHODS: A Markov model was developed in Microsoft Excel to estimate lifetime health consequences and resulting costs among cohort of 1,000 patients with BC with bone metastasis, for three intervention scenarios, namely denosumab (once every 4 weeks), ZA (once every 4 weeks), and ZA (once every 12 weeks). The health outcomes were measured in terms of SREs averted and quality-adjusted life-years (QALYs) gained. The cost of each intervention scenario was measured using both the health system and the patient's perspectives. Indirect costs because of lost productivity were not included. The future costs and outcomes were discounted at the standard rate of 3%. RESULTS: Over a lifetime, the incremental number of SREs averted with use of denosumab once every 4 weeks (compared with ZA once every 4 weeks and once every 12 weeks) among patients with luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple negative breast cancer were estimated as 0.39, 0.26, 0.25, and 0.19, respectively. The number of QALYs lived were slightly higher in the denosumab arm (1.45-2.80) compared with ZA once every 4 weeks and once every 12 weeks arms (1.44-2.78). However, denosumab once every 4 weeks was not found to be a cost-effective alternative for either of the four molecular subtypes of breast cancer. ZA once every 12 weeks was found to be a cost-effective option with an average cost-effectiveness ratio ranging between â¹68,254 and â¹73,636. CONCLUSION: ZA once every 12 weeks is the cost-effective treatment option for BC with bone metastases in India. The present study findings hold significance for standard treatment guidelines under India's government-funded health insurance program.
Asunto(s)
Conservadores de la Densidad Ósea , Neoplasias Óseas , Neoplasias de la Mama , Humanos , Femenino , Denosumab/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Análisis de Costo-Efectividad , Imidazoles/uso terapéutico , Análisis Costo-Beneficio , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Ácido Zoledrónico/uso terapéuticoRESUMEN
BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.
Asunto(s)
Mieloma Múltiple , Neoplasias Testiculares , Masculino , Femenino , Humanos , Calidad de Vida , Encuestas y Cuestionarios , EscolaridadRESUMEN
BACKGROUND: The standard dose (SD) of horse anti-thymocyte globulin (hATG) ATGAM (Pfizer, USA) or its biosimilar thymogam (Bharat Serum, India) for the treatment of Aplastic Anemia (AA) is 40 mg/kg/day for 4 days in combination with cyclosporine. Data on the impact of hATG dose on long-term outcomes are limited. Here, we describe our comparative experience using 25 mg/kg/day (low-dose [LD]) hATG for 4 days with SD for the treatment of AA. METHODS: We retrospectively studied patients with AA (age > 12 years) who received two doses of hATG combined with cyclosporine. Among 93 AA patients who received hATG, 62 (66.7%) and 31 (33.3%) patients received LD and SD hATG with cyclosporine, respectively. Among these,seventeen(18.2%) patients also received eltrombopag with hATG and cyclosporine. Overall response rates [complete response (CR) and partial response (PR)] of LD and SD hATG groups at 3 months (50% vs. 48.4%; p = 0.88), 6 months (63.8% vs. 71.4%; p = 0.67), and 12 months (69.6% vs. 79.2%; p = 0.167) were comparable. The mean (Standard Deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival was 82.1 (4.6)% and 70.9 (5.5)% for the study population. The mean (standard deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received LD hATG versus SD hATG dose was 82.9 (5·3)% versus 74.8 (10·3)% (P = 0·439), and 75.2 (6.2)% versus 61.4(11.2)% (P = 0·441). CONCLUSION: Our study revealed that the response rates of patients with AA and LD were similar to those of patients with SD to hATG combined with cyclosporine in a real-world setting.
RESUMEN
BACKGROUND: Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. METHODS: A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of â¹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. RESULTS: Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone) alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of â¹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [â¹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of â¹1,46,890 (US$1,927.7). CONCLUSION: At the current WTP threshold of one-time per capita GDP (â¹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of â¹40,671 (US$34) and â¹97,639 (US$1,281) per QALY gained, respectively.
Asunto(s)
Bortezomib , Análisis Costo-Beneficio , Trasplante de Células Madre Hematopoyéticas , Cadenas de Markov , Mieloma Múltiple , Años de Vida Ajustados por Calidad de Vida , Mieloma Múltiple/tratamiento farmacológico , Humanos , India , Trasplante de Células Madre Hematopoyéticas/economía , Bortezomib/uso terapéutico , Bortezomib/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Dexametasona/uso terapéutico , Dexametasona/economía , Dexametasona/administración & dosificación , Masculino , Femenino , Lenalidomida/uso terapéutico , Persona de Mediana Edad , Ciclofosfamida/uso terapéutico , Ciclofosfamida/economía , Talidomida/economía , Talidomida/uso terapéutico , Talidomida/análogos & derivados , Antineoplásicos/economía , Antineoplásicos/uso terapéutico , Anticuerpos MonoclonalesRESUMEN
Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.
RESUMEN
Inherited iron metabolism defects are possibly missed or underdiagnosed in iron-deficient endemic settings because of a lack of awareness or a methodical screening approach. Hence, we systematically evaluated anemia cases (2019 to 2021) based on clinical phenotype, normal screening tests (high-performance liquid chromatography, α gene sequencing, erythrocyte sedimentation rate, C-reactive protein, and tissue transglutaminase), and abnormal iron profile by targeted next-generation sequencing (26-gene panel) supplemented with whole-exome sequencing, multiplex ligation probe amplification/mitochondrial DNA sequencing, and chromosomal microarray. Novel variants in ALAS2, STEAP3, and HSPA9 genes were functionally validated. A total of 290 anemia cases were screened, and 41 (14%) enrolled for genomic testing as per inclusion criteria. Comprehensive genomic testing revealed pathogenic variants in 23 of 41 cases (56%). Congenital sideroblastic anemia was the most common diagnosis (14/23; 61%), with pathogenic variations in ALAS2 (n = 6), SLC25A38 (n = 3), HSPA9 (n = 2) and HSCB, SLC19A2, and mitochondrial DNA deletion (n = 1 each). Nonsideroblastic iron defects included STEAP3-related microcytic anemia (2/23; 8.7%) and hypotransferrenemia (1/23; 4.3%). A total of 6 of 22 cases (27%) revealed a non-iron metabolism gene defect on whole-exome sequencing. Eleven novel variants (including variants of uncertain significance) were noted in 13 cases. Genotype-phenotype correlation revealed a significant association of frameshift/nonsense/splice variants with lower presentation age (0.8 months versus 9 years; P < 0.01) compared with missense variants. The systematic evaluation helped uncover an inherited iron defect in 41% (17/41) of cases, suggesting the need for active screening and awareness for these rare diseases in an iron-deficient endemic population.
Asunto(s)
Anemia Sideroblástica , Hierro , Humanos , Lactante , Hierro/metabolismo , Mutación , Anemia Sideroblástica/epidemiología , Anemia Sideroblástica/genética , Anemia Sideroblástica/diagnóstico , Genómica , ADN Mitocondrial , Proteínas de Transporte de Membrana/genética , 5-Aminolevulinato Sintetasa/genética , 5-Aminolevulinato Sintetasa/metabolismoRESUMEN
Permanent stains such as trichrome have better sensitivity but are time-consuming and the fixative includes toxic mercuric chloride. Thus, a newer modification was tested and found to be a superior, faster and safer staining technique for intestinal parasitic detection. Our study lasted 9 months and a single stool sample was collected from each enrolled patient. We evaluated classical trichrome (T1 - using Schaudinn fixative) with newer modifications, which involved different fixatives with mordant combinations (T2 - acetic acid + hydrated aluminium sulphate, T3 - citric acid + copper sulphate hydrate). Conventional PCR targeting Entamoeba histolytica, Giardia lamblia and Cryptosporidium spp. was taken as the reference. Out of 175 stool samples, 25.1% protozoa were identified by wet mount, 24% by each T1 and T2, 25.7% by T3. Statistically, T3 and T2 had higher sensitivity as compared to T1 and wet mount when PCR was used as reference.