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Biomedical subjects

Ritu Gupta

Publications and source records attributed to Ritu Gupta.

16 recordsLinked to original sources

Genomic Alterations in Multiple Myeloma: A Comprehensive Landscape.

UNLABELLED: Multiple myeloma (MM) is a biologically heterogeneous plasma cell malignancy in which cytogenetic abnormalities play a key role in disease prognosis. This study evaluates the spectrum of genomic aberrations in newly diagnosed multiple myeloma (NDMM) patients, with a focus on high-risk cytogenetic profiles, including double-hit (DHMM), and triple-hit multiple myeloma (THMM). This is a retrospective analysis of NDMM patients, reviewing clinical and laboratory data for baseline characteristics, cytogenetics, therapy, and outcomes. Patients were categorized based on the cytogenetic abnormalities. Double-hit MM was defined by the coexistence of two high-risk abnormalities and triple-hit MM was defined by coexistence of three or more high-risk abnormalities. Survival outcomes were assessed using Kaplan-Meier analysis and Cox regression models using SigmaPlot (version 15). A total of 314 NDMM cases (205 Male: 109 Female; median age 58 years) enrolled between 2014 and 2021 were evaluated. Using the Revised International Staging System (R2-ISS), most patients were in stage 2 (41.1%) and stage 3 (38.2%). Cytogenetic analysis revealed one or more high-risk abnormalities in 43% of cases. Among the high-risk group, one, two and three or more high-risk abnormalities were observed in 89 (28%), 35 (11%), and 11 (4%) patients, respectively. THMM cases exhibited the poorest outcomes [median overall survival (OS):7 months], in comparison to DHMM (OS: 33 months), SHMM (OS: 40 months), and patients without high-risk features (OS: 60 months). Cox regression analysis confirmed that THMM patients had a 3.6-fold increased risk of death (HR: 3.677; 95% CI: 2.219-7.915; p&#x2009;<&#x2009;0.001) and 4-fold increased risk of progression (HR: 4.191; 95% CI: 1.897-7.126; p&#x2009;<&#x2009;0.001) compared to patients without any high-risk abnormalities. Among 67 patients undergoing autologous stem cell transplant (ASCT), high risk abnormalities were significantly associated with shorter OS (HR: 2.409; 95% CI: 1.094-5.291; p&#x2009;=&#x2009;0.029, 111 months for ASCT without high-risk vs. 78 months for ASCT with high- risk abnormalities) and shortened PFS (HR: 2.379; 95% CI: 1.285-4.403; p&#x2009;=&#x2009;0.006, 85 months for ASCT without high-risk vs. 34 months with high-risk abnormalities). Double and triple-hit MM constitute 14.6% of NDMM cases, indicating poor survival and early disease progression. Comprehensive cytogenetic profiling at diagnosis and post-ASCT has the potential to improve risk stratification and guide individualized treatment strategies for high-risk MM patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02284-5.

Cytogenetic↗

Phylogeny and evolution of SARS-CoV-2 during Delta and Omicron variant waves in India.

SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India. Delta variant was reported in patients without comorbidity (97%), while Omicron BA.2 was reported in patients with comorbidity (77%). Tissue adaptation studies brought forth higher propensity of Omicron variants to bronchial tissue than lung, contrary to observation in Delta variants from Delhi. Study of codon usage pattern distinguished the prevalent variants, clustering them separately, Omicron BA.2 isolated in February grouped away from December strains, and all BA.2 after December acquired a new mutation S959P in ORF1b (44.3% of BA.2 in the study) indicating ongoing evolution. Loss of critical spike mutations in Omicron BA.2 and gain of immune evasion mutations including G142D, reported in Delta but absent in BA.1, and S371F instead of S371L in BA.1 could explain very brief period of BA.1 in December 2021, followed by complete replacement by BA.2. Higher propensity of Omicron variants to bronchial tissue, probably ensured increased transmission while Omicron BA.2 became the prevalent variant possibly due to evolutionary trade-off. Virus evolution continues to shape the epidemic and its culmination.Communicated by Ramaswamy H. Sarma.

SARS-CoV-2↗

Photoprotection by 1,25 dihydroxyvitamin D3 is associated with an increase in p53 and a decrease in nitric oxide products.

Vitamin D is produced in skin by UVB radiation (290-320 nm) acting on 7-dehydrocholesterol. The hypotheses that the active vitamin D hormone, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), would increase the survival of skin cells after UV irradiation and that surviving cells after 1,25(OH)2D3 treatment would have no increase in DNA damage were tested. The survival of keratinocytes post-UVR was significantly greater after treatment with 1,25(OH)2D3 compared to vehicle (P<0.01). Significant reductions in thymine dimers (TDs) in surviving keratinocytes after UVR were noted in the presence of 1,25(OH)2D3 (P<0.001). Nuclear p53 protein expression increased after UVR and was significantly higher in keratinocytes treated with 1,25(OH)2D3 (P<0.01), whereas NO products were significantly reduced (P<0.05). Both the increase in nuclear accumulation of p53 protein and reduced formation of nitric oxide products may contribute to the reduction in TDs seen with 1,25(OH)2D3 after UVR. Reductions in numbers of sunburn cells (P<0.01) and in TDs (P<0.05) were observed 24 hours after UVR in skin sections from Skh:hr1 mice treated with 1,25(OH)2D3. These results are consistent with the proposal that the vitamin D system in skin may be part of an intrinsic protective mechanism against UV damage.

Animals↗

Application of flow cytometry in detection of red-cell-bound IgG in Coombs-negative AIHA.

Coombs negative autoimmune hemolytic anemia (AIHA) is characterized by laboratory evidence of in vivo hemolysis along with a negative direct antiglobulin test (DAT) performed by conventional tube technique (CTT) in clinically suspected AIHA patients. The sensitive gel test (GT) and flow cytometry (FC) can effectively diagnose such patients where CTT does not detect low level of red cell autoantibodies. We investigated the use of FC in the serological evaluation of CTT DAT negative AIHA and its comparison with GT DAT. Of the 50 patients with suspected AIHA, CTT DAT was negative in 5 patients (Coombs negative AIHA). GT DAT could detect red cell autoantibodies in 4 of these 5 patients. Monospecific GT DAT showed IgG and/or C3d as the responsible autoantibody. FC was considered as reactive when MFI was >3.6 (mean of 20 healthy negative volunteers +2SD). FC was reactive in all five Coombs negative AIHA patients. The mean MFI in five known CTT DAT positive samples taken for comparison was significantly higher compared to 5 DAT negative AIHA (18.3 +/- 7.78 vs. 7.88 +/- 1.35, p < 0.05). There was poor correlation between strength of GT DAT and MFI by FC. We conclude that FC is more sensitive test than the CTT and helps in the serological diagnosis of Coombs negative AIHA. However, in resource poor settings, GT DAT can be a good alternative to FC.

Adolescent↗

Chronic urticaria due to Blastocystis hominis.

A 24-year-old woman had a 9-week history of second to third daily urticaria that began after an episode of contact urticaria to topical bufexamac. She was found to have an underlying gastrointestinal infection with Blastocystis hominis. This was thought to be clinically relevant as she had a history of mild chronic diarrhoea. After treatment of the Blastocystis hominis, her urticaria ceased. This could indicate the importance of performing stool microscopy and culture on all patients with chronic urticaria of unknown aetiology. The relationship of urticaria to intestinal parasites and the possibility that non-steroidal anti-inflammatory medications could act as cofactors that help precipitate an urticarial reaction is discussed.

Administration, Cutaneous↗

Primary Hodgkin's disease of spleen--a case report.

Primary malignant lymphoma of spleen is rare with primary Hodgkin's disease (HD) of spleen being rarer. The diagnosis of primary splenic HD is usually made on the histopathological examination of the splenectomy specimen. We report an interesting case of primary HD of spleen in a child emphasizing its rarity and the role of fine needle aspirate cytology in early diagnosis and non-surgical management of this entity.

Biopsy, Fine-Needle↗

A comparison between povidone-ethylcellulose and povidone-eudragit transdermal dexamethasone matrix patches based on in vitro skin permeation.

The present study was designed to develop a suitable matrix type transdermal drug delivery system (TDDS) of dexamethasone using blends of two different polymeric combinations, povidone (PVP) and ethylcellulose (EC) and Eudragit with PVP. Physical studies including moisture content, moisture uptake, flatness to study the stability of the formulations and in vitro dissolution of the experimental formulations were performed to determine the amount of dexamethasone present in the patches were performed and scanning electron microscopy (SEM) photographs of the prepared TDDS were taken to see the drug distribution pattern. Drug-excipient interaction studies were carried out using Fourier transform infrared (FTIR) spectroscopic technique. In vitro skin permeation study was conducted in a modified Franz's diffusion cell. All the formulations were found to be suitable for formulating in terms of physicochemical characteristics and there was no significant interaction noticed between the drug and polymers used. In vitro dissolution studies showed that the drug distribution in the matrix was homogeneous and the SEM photographs further demonstrated this. The formulations of PVP:EC provided slower and more sustained release of drug than the PVP:Eudragit formulations during skin permeation studies and the formulation PVP:EC (1:5) was found to provide the slowest release of drug. Based on the above observations, it can be reasonably concluded that PVP-EC polymers are better suited than PVP-Eudragit polymers for the development of TDDS of dexamethasone.

Administration, Cutaneous↗

Interleukin-6 protects hepatocytes from CCl4-mediated necrosis and apoptosis in mice by reducing MMP-2 expression.

BACKGROUND/AIMS: Interleukin-6 stimulates liver regeneration and promotes hepatoprotection following experimental liver injury, but underlying mechanisms have not been fully characterized. Because studies suggest matrix metalloproteinase-2 (MMP-2) may promote liver injury, we examined whether IL-6 exerted its protective effects via regulation of MMP-2. METHODS: MMP-2 was analyzed in livers of IL-6-/- and IL-6+/+ mice following CCl(4) administration. IL-6-/- mice were pretreated with IL-6 and liver histology and MMP-2 expression were examined after liver injury. IL-6-/- mice were treated with an MMP-2 inhibitor and assessment of injury (histology and serum ALT levels), apoptosis by TUNEL assay, and hepatocyte proliferation by BRDU-labeling was performed. These studies were complemented by analysis of cultured stellate cells. RESULTS: MMP-2 mRNA, protein, and activity was increased in IL-6-/- livers. Restoration of IL-6 signaling in IL-6-/- mice rescued injury and restored MMP-2 expression to wild-type levels. Furthermore, pharmacologic inhibition of MMP-2 decreased hepatocellular injury and apoptosis in IL-6-/- mice. In cultured stellate cells, recombinant IL-6 suppressed endogenous MMP-2 mRNA and protein expression. CONCLUSIONS: IL-6 may be hepatoprotective in acute injury through down-regulation of MMP-2. These findings suggest a role for MMP-2 in amplifying liver injury in vivo.

Acute Disease↗

The legacy of a community mobilisation project to reduce alcohol related harm.

The Community Mobilisation for the Prevention of Alcohol Related Injury (COMPARI) project was established to investigate how alcohol related harm could be reduced within the Geraldton community through community action. Twenty-two major component activities were carried out over three years. On completion of the demonstration phase the project was taken over by the community and evolved into the region's main alcohol and drug service provider. This research seeks to identify the legacy of COMPARI from interviews with 23 key informants and from serial measures of alcohol consumption and harm. Key informants indicated that the original community prevention focus of the project has been diluted and there is more emphasis on individual prevention through education and training. A culture of intersectoral collaboration on alcohol issues has endured and this contributes to better use of resources and higher levels of treatment referral. There was also strong acknowledgement that the local committee was crucial in sustaining the project. Since the inception of COMPARI, local alcohol consumption has decreased and a proxy measure of alcohol harm, weekend, night, hospital accident and emergency occasions of service, also indicates better outcomes in Geraldton. The original project initiated cultural and structural change in the way alcohol problems are dealt with in Geraldton and this has produced on-going benefit for the community.

Alcohol Drinking↗

Acute basophilic leukemia: case report.

The term "basophilic leukemia" has been in use for 75 years. However, consistent diagnostic criteria are lacking. This is due to the rarity of the disease and to the routine unavailability of special tests that are often required to confirm a diagnosis. We report an unusual case of acute basophilic leukemia in a child who was referred to our Center, arriving with partially treated acute lymphoblastic leukemia. Basophilic differentiation on light microscopy was evident from the coarse basophilic granules in blasts, a progressive maturation of blasts toward basophils, and toluidine positivity on cytochemistry. Blasts showed a myeloid immunophenotype (CD13+, CD33+, CD117+) with a characteristic dual positivity for CD34 and CD25, highly suggestive of basophilic nature of the blasts. Conventional cytogenetic studies revealed translocation t(8;21)(q22;q22). A diagnosis of acute basophilic leukemia with t(8;21) was made. Review of pre-therapy slides showed features consistent with AML-M2 with basophilia. There were no basophilic blasts. With these features, a diagnosis of acute basophilic leukemia secondary to AML-M2 was made. In our patient, basophilic leukemia appears to have evolved from selective clonal proliferation of "basophil-committed blasts" during the course of the disease in a case of AML-M2 with basophilia.

Antigens, CD↗

Flow cytometric analysis of CD5+ B cells: a frame of reference for minimal residual disease analysis in chronic lymphocytic leukemia.

Recent reports suggest that CD5+ B cells constitute up to 47% of the total B cells in normal peripheral blood (PB), a finding that would restrict the sensitivity of the CD5/CD19 flow cytometric assay for minimal residual disease (MRD) analysis in chronic lymphocytic leukemia (CLL). We studied 40 normal samples (PB, 20; bone marrow [BM], 20) using CD5-fluorescein isothiocyanate (FITC)/CD19-phycoerythrin (PE) immunostaining to evaluate the reference range of CD5+ B cells. The mean percentage of CD5+ B cells per total number of B cells was 12.2% (range, 3.6%-23.9%) in PB and 11.7% (range, 4.4%-19.5%) in BM. On serial dilution, this assay could detect 1 CLL cell in 1,000 leukocytes (sensitivity, 0. 1%). A distinct "bright" CD5+ B-cell subpopulation, consistent with a CLL-like-phenotype, was observed in 3 samples. Our results suggest that the CD5-FITC/CD19-PE assay has a clinically useful sensitivity for MRD analysis in CLL. The usefulness of this assay as a screening tool to identify the earliest stage of indolent CLL needs further study.

Adult↗

Touch imprint cytology of axillary lymph nodes after neoadjuvant chemotherapy in patients with breast carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NC) reportedly downstages axilla in approximately one-third of patients with locally advanced breast carcinoma (LABC). Postchemotherapy axillary lymph node status is an important prognostic factor. In the current study, the authors evaluated the reliability of touch imprint cytology (TIC) in detecting axillary lymph node metastasis after NC and identified chemotherapy-induced changes that may influence this assessment. METHODS: Thirty-three patients with LABC were studied. Seventeen patients had received chemotherapy before surgery (NC group) and 16 patients had not (non-NC group). Touch imprints were made from either the largest axillary lymph node (in 13 patients from the NC group and 16 patients from the non-NC) or the sentinel lymph node (in 4 patients from the NC group). Imprints from the NC group were evaluated for metastasis and were correlated with histopathology. Touch imprints from both groups were compared for cellularity, tumor load, necrosis/degeneration, and histiocytes. RESULTS: Cytologic evaluation for metastasis was 100% concordant with histopathology in all 17 patients from the NC group (9 positive results [53%] and 8 negative results [47%]). The presence of few tumor cells in sparsely cellular imprints that exhibited necrosis (two patients) and the presence of only degenerating/necrotic tumor cells (two patients) were two cytologic patterns unique to post-NC imprints that may have influenced their accurate assessment. CONCLUSIONS: TIC was found to be reliable for the intraoperative evaluation of axillary lymph node metastasis after NC. However, a careful examination is warranted in sparsely cellular imprints, because there is the possibility of overlooking a small group of tumor cells. To the authors' knowledge, the significance of finding extensive necrosis in axillary lymph nodes after NC is not known and may be investigated.

Adult↗

Development and in vitro evaluation of diltiazem hydrochloride transdermal patches based on povidone-ethylcellulose matrices.

To select a suitable formulation for the development of transdermal drug-delivery system of diltiazem hydrochloride. Transdermal patches of the drug, employing different ratios of polymers, ethylcellulose (EC), and povidone (PVP) were developed and evaluated for the potential drug delivery using depilated freshly excised abdominal mouse skin. The influence of different film compositions on in vitro drug permeation into receptor fluid were studied using a modified Franz diffusion cell. The cumulative amount of drug was found to be proportional to the square root of time, i.e., Higuchi kinetics. From this study, it was concluded that the films composed of povidone:ethylcellulose (1:2) should be selected for the development of transdermal drug-delivery system of diltiazem hydrochloride, using a suitable adhesive layer and backing membrane, for potential therapeutic use.

Administration, Cutaneous↗

A study from Nepal showing no correlation between lichen planus and hepatitis B and C viruses.

A total number of 86 cases of Lichen planus (LP) were seen over a period of one and a half years. This constituted 0.58% of 14,833 new dermatological patients seen. Hepatitis B and C viral (HBV & HCV) serology was carried out in 64 patients and 43 age and sex matched controls. In the examined patients, 35 (54.27%) had the skin lesions only. Oral lesions were present in 15 (23.4%) of the patients in addition to skin lesions, while 14 (21.9%) had only oral involvement. Serology for HBsAg and HCV was negative in all types of LP patients and the controls. In Nepal, HBV and HCV seem to be not important in the pathogenesis of LP.

Adult↗

Metastatic anaplastic oligodendroglioma simulating acute leukemia. A case report.

BACKGROUND: Anaplastic oligodendroglioma (OG) is an uncommon tumor that rarely metastasizes outside the central nervous system. Spread to the bone marrow (BM) is so rare that when it occurs in the course of follow-up of a case of OG, a disseminated second primary tumor may be a more likely possibility unless BM examination provides evidence to the contrary. Potentially misleading cytologic features of metastatic anaplastic OG can be seen in a BM touch preparation. CASE: A 50-year-old man had undergone left frontal lobectomy in September 1999 for anaplastic OG and presented seven months later with evidence, on BM scan, of focal abnormal uptake at multiple sites. Bone marrow biopsy confirmed OG secondaries, which, on the touch preparation, appeared not only in clusters but also as single cells, simulating acute leukemia. CONCLUSION: The morphology of anaplastic OG metastatic to BM simulates acute leukemia, as seen on the BM touch preparation. This is relevant particularly in the context of anaplastic OG on follow-up. This diagnostic pitfall can be heightened if a BM aspirate rather than biopsy is performed. Metastatic OG can be added to the list of tumors that metastasize to BM as single cells.

Acute Disease↗

Superior sagittal sinus thrombosis and Budd-Chiari syndrome due to paroxysmal nocturnal hemoglobinuria managed with transjugular intrahepatic portosystemic shunt: a case report.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), caused by somatic mutation of hematopoietic cells, is associated with complement-mediated hemolysis and a hypercoagulable state. Thrombotic complications in this disease are associated with reduced survival. We report a patient with PNH complicated by intracranial venous thrombosis and Budd-Chiari syndrome, who was managed with transjugular intrahepatic portosystemic shunt. CASE PRESENTATION: A 26-year-old man presented with thrombosis of the superior sagittal and right sigmoid sinuses. Initial investigations did not reveal any underlying cause. Nine months later, he developed hepatic venous thrombosis. At this time, Ham test was positive. Flow cytometry confirmed the diagnosis of PNH. The patient was treated with transjugular intrahepatic portosystemic shunt; one episode of stent blockage one month later was managed successfully with balloon dilatation and restenting. CONCLUSION: PNH should be considered in patients with unexplained venous thrombosis. Thrombosis in these patients needs to be managed with prolonged anticoagulation. For Budd-Chiari syndrome in patients with underlying PNH, transjugular intrahepatic portosystemic shunt may be a good option but caution is needed to prevent stent occlusion.

Adult↗