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1.
Indian J Med Microbiol ; 49: 100605, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38734140

RESUMO

Cerebral phaeohyphomycosis (CP) stands as an exceedingly uncommon yet severe type of fungal infection affecting the central nervous system, attributable to dematiaceous fungi. Despite the patient's immune status, CP is associated with grave prognosis. In the present study, authors describe the first case of left thalamic fungal abscess due to Rhinocladiella mackenziei in an immunocompetent 39-year-old male patient in Jaipur, Rajasthan. Early diagnosis by direct microscopy of aspirated pus and extensive management with surgical excision and prolonged antifungal coverage showed favourable outcome. The present case is one of the few cases documented globally who has survived.

2.
J Clin Oncol ; : JCO2400541, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38754041

RESUMO

PURPOSE: To update the ASCO guideline on the management of cancer-related fatigue (CRF) in adult survivors of cancer. METHODS: A multidisciplinary panel of medical oncology, geriatric oncology, internal medicine, psychology, psychiatry, exercise oncology, integrative medicine, behavioral oncology, nursing, and advocacy experts was convened. Guideline development involved a systematic literature review of randomized controlled trials (RCTs) published in 2013-2023. RESULTS: The evidence base consisted of 113 RCTs. Exercise, cognitive behavioral therapy (CBT), and mindfulness-based programs led to improvements in CRF both during and after the completion of cancer treatment. Tai chi, qigong, and American ginseng showed benefits during treatment, whereas yoga, acupressure, and moxibustion helped to manage CRF after completion of treatment. Use of other dietary supplements did not improve CRF during or after cancer treatment. In patients at the end of life, CBT and corticosteroids showed benefits. Certainty and quality of evidence were low to moderate for CRF management interventions. RECOMMENDATIONS: Clinicians should recommend exercise, CBT, mindfulness-based programs, and tai chi or qigong to reduce the severity of fatigue during cancer treatment. Psychoeducation and American ginseng may be recommended in adults undergoing cancer treatment. For survivors after completion of treatment, clinicians should recommend exercise, CBT, and mindfulness-based programs; in particular, CBT and mindfulness-based programs have shown efficacy for managing moderate to severe fatigue after treatment. Yoga, acupressure, and moxibustion may also be recommended. Patients at the end of life may be offered CBT and corticosteroids. Clinicians should not recommend L-carnitine, antidepressants, wakefulness agents, or routinely recommend psychostimulants to manage symptoms of CRF. There is insufficient evidence to make recommendations for or against other psychosocial, integrative, or pharmacological interventions for the management of fatigue.Additional information is available at www.asco.org/survivorship-guidelines.

3.
J Clin Oncol ; 42(15): 1830-1850, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38502889

RESUMO

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Oral Biol Craniofac Res ; 14(1): 33-38, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481655

RESUMO

The permanence of deep subgingival restorations are questionable both functionally and biologically. Crown lengthening is one of the traditionally performing procedures to visualize and relocate the deep margins, but the limitations of the invasive surgical procedure are anatomical complications like exposure of root concavities or furcation, violation of biological width, post operative discomfort because of sutures or periodontal packs; and less patient compliance. Other than crown lengthening, researchers tried some other techniques like modified matrix adaptation technique, using retraction cord, making holes in matrix band and flowing resin modified glass ionomer cement (RMGIC) to the root or cervical caries, orthodontic extrusion. But most of these procedures are failed to give adequate clinical success. Deep margin elevation (DME) is one of the minimally invasive and successful procedure performing in deep subgingival caries. But the evidences and knowledge in this technique is limited among practitioners. This review is to evaluate the applicability of DME, the current clinical concepts, techniques and materials for DME; and a comparison with traditionally used various techniques for cervical margin relocation also concluding that currently available various clinical parameters with this technique.

5.
Nicotine Tob Res ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477033

RESUMO

INTRODUCTION: According to the Global Adult Tobacco Survey-2, India, 7.5% of pregnant women are tobacco users with a high prevalence of smokeless tobacco use in rural India. Although pregnant women may receive advice to quit tobacco, lack of knowledge on providing cessation support among healthcare workers results in missed opportunities. Community Health Workers (CHWs) play a significant role in maternal and child health (MCH) programs. Thus, task-shifting for providing cessation support by CHWs was planned and the perceptions and attitudes of concerned stakeholders were explored. METHOD: A pre-implementation qualitative study was conducted in four states of India within existing rural, community-based MCH program settings. Implementation research frameworks were used to develop data collection tools and for inductive and deductive thematic analysis. In-depth interviews were conducted with stakeholders (n=28) like coordinators, pregnant women and village functionaries of the government health system. Four focus groups were conducted with female CHWs (n=24). RESULTS: Stakeholders intended to adopt the intervention as objectives of the cessation intervention were aligned with the aims of the MCH program. CHWs related to their role in task-shifting and understood the context for implementing the intervention within the MCH program. Pregnant women expressed openness to receiving cessation support from CHWs acting as a facilitator for task-shifting. Barriers anticipated were the additional workload and time required for CHWs to implement the intervention. CONCLUSION: Task-shifting to female CHWs for screening tobacco users, providing brief advice and cessation support within the MCH program was perceived to be acceptable, adoptable and feasible. IMPLICATIONS: The study builds insight into the process of developing a grounded approach for the integration of tobacco cessation intervention into a rural, community-based antenatal care setting by task shifting to female community health workers for providing cessation support to pregnant women. The study fills gaps in the literature related to establishing tobacco cessation interventions for pregnant women. The delineated efforts in integration of the intervention and task shifting can be replicated in other developing countries, especially in rural communities within South Asian and Southeast Asian regions having cultural practices, community-based healthcare structures and tobacco consumption patterns that are comparable to India.

6.
ACS Chem Neurosci ; 15(5): 916-931, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38369717

RESUMO

Novel insights into the etiology of metabolic disorders have recently been uncovered through the study of metabolite amyloids. In particular, inborn errors of metabolism (IEMs), including gout, Lesch-Nyhan syndrome (LNS), xanthinuria, citrullinemia, and hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, are attributed to the dysfunction of the urea cycle and uric acid pathway. In this study, we endeavored to understand and mechanistically characterize the aggregative property exhibited by the principal metabolites of the urea cycle and uric acid pathway, specifically hypoxanthine, xanthine, citrulline, and ornithine. Employing scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM), we studied the aggregation profiles of the metabolites. Insights obtained through molecular dynamics (MD) simulation underscore the vital roles of π-π stacking and hydrogen bonding interactions in the self-assembly process, and thioflavin T (ThT) assays further corroborate the amyloid nature of these metabolites. The in vitro MTT assay revealed the cytotoxic trait of these assemblies, a finding that was substantiated by in vivo assays employing the Caenorhabditis elegans (C. elegans) model, which revealed that the toxic effects were more pronounced and dose-specific in the case of metabolites that had aged via longer preincubation. We hence report a compelling phenomenon wherein these metabolites not only aggregate but transform into a soft, ordered assembly over time, eventually crystallizing upon extended incubation, leading to pathological implications. Our study suggests that the amyloidogenic nature of the involved metabolites could be a common etiological link in IEMs, potentially providing a unified perspective to study their pathophysiology, thus offering exciting insights into the development of targeted interventions for these metabolic disorders.


Assuntos
Hiperamonemia , Ornitina/deficiência , Distúrbios Congênitos do Ciclo da Ureia , Ácido Úrico , Animais , Caenorhabditis elegans , Distúrbios Congênitos do Ciclo da Ureia/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/patologia , Amiloide/metabolismo , Ornitina/metabolismo , Ureia
7.
Curr Oncol Rep ; 26(1): 34-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38224426

RESUMO

PURPOSE OF REVIEW: Male breast cancer is a relatively uncommon and rare disease that is often managed based on evidence adopted from trials pertaining to female breast cancer due to low accrual rates or exclusion of males. This is despite the known differences in the biology and epidemiology of this condition. This review provides an update regarding the management and surveillance of male breast cancer. RECENT FINDINGS: Men with breast cancer tend to undergo more extensive surgery in the breast and axilla. The outcomes of male breast cancer compared to a similar subtype of female breast cancer appear worse when matched for stage. Systemic therapies remain predominantly based on recommendations for female breast cancer, although tamoxifen is the more optimal endocrine therapy for men than women. Surveillance with mammograms is recommended for patients harboring a breast cancer susceptibility gene but is otherwise not advised for men who have undergone a mastectomy. Notably, the role of other imaging modalities, including ultrasound and magnetic resonance imaging, is minimal. Although the focus on survivorship care among men is low, it is abundantly clear that this is a stigmatizing diagnosis for men, and they suffer from long-term physical and psychological sequelae following a diagnosis and treatment of breast cancer. In summary, providing more gender-inclusive care and advocating for increased representation of men in prospective breast cancer studies and clinical trials may help improve outcomes and provide enhanced support for this population.


Assuntos
Neoplasias da Mama Masculina , Neoplasias da Mama , Feminino , Humanos , Masculino , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/terapia , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Mastectomia , Sobrevivência , Estudos Prospectivos , Mamografia
8.
Transl Oncol ; 40: 101827, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38042138

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are the most devastating diseases in India and southeast Asia. It is a preventable and curable disease if detected early. Tobacco and alcohol consumption are the two major risk-factors but infection of high-risk HPVs are also associated with development of predominantly oral and oropharyngeal carcinomas. Interestingly, unlike cervical cancer, HPV-induced HNSCCs show good prognosis and better survival in contrast, majority of tobacco-associated HPV-ve HNSCCs are highly aggressive with poor clinical outcome. Biomarker analysis in circulatory body-fluids for early cancer diagnosis, prognosis and treatment monitoring are becoming important in clinical practice. Early diagnosis using non-invasive saliva for oral or other diseases plays an important role in successful treatment and better prognosis. Saliva mirrors the body's state of health as it comes into direct contact with oral lesions and needs no trained manpower to collect, making it a suitable bio-fluid of choice for screening. Saliva can be used to detect not only virus, bacteria and other biomarkers but variety of molecular and genetic markers for an early detection, treatment and monitoring cancer and other diseases. The performance of saliva-based diagnostics are reported to be highly (≥95 %) sensitive and specific indicating the test's ability to correctly identify true positive or negative cases. This review focuses on the potentials of saliva in the early detection of not only HPV or other pathogens but also identification of highly reliable gene mutations, oral-microbiomes, metabolites, salivary cytokines, non-coding RNAs and exosomal miRNAs. It also discusses the importance of saliva as a reliable, cost-effective and an easy alternative to invasive procedures.

10.
Appl Opt ; 62(21): 5786-5793, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37707197

RESUMO

We demonstrate a cost-effective and high-throughput fabrication technique to deposit colloidal nanoparticles on a patterned polymer substrate using a capillary-assisted self-assembly method over a large area. In particular, we fabricate optical gratings using gold nanoparticles and a polymer substrate. We show the versatility of the technique over different nanoparticle diameters and grating periodicities. Through both experiments and simulations, we show enhanced transmission in the first-order diffraction of the gold-polymer grating as compared to the air-polymer grating. Our fabrication technique also enables the transfer of the nanoparticle pattern from the polymer substrate to any desired surface. Here we demonstrate the transfer of the nanoparticle grating structure to the tip of optical fibers.

11.
J Med Signals Sens ; 13(3): 233-238, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622043

RESUMO

Complete edentulism is one of the most common problems encountered by geriatric individuals. With advanced aging, despite attempts made to retain natural dentition, loss of entire teeth is yet observed. For precise denture fabrication, a digital sensor device was used during the making procedure. The use of sensor device aided in better appreciation and more retentiveness of denture.

12.
Am J Cancer Res ; 13(6): 2564-2571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424818

RESUMO

Neoadjuvant chemotherapy (NAC) with Anti-Human Epidermal Growth Factor Receptor 2 (Anti-HER2) agents increase rates of pathologic complete response (pCR) in stage II-III, HER2+ breast cancer (BC). Several retrospective studies show HER2 amplification discordance from biopsy to post-NAC residual disease (RD). This phenomenon has unclear prognostic significance. This data was obtained from patients with HER2+ BC treated with NAC between 2018-2021 at our institution. Patients with biopsy and surgical specimens at our institution were analyzed. PCR was defined as ypT0/is N0, and HER2 status on RD was evaluated. 2018 HER2 ASCO/CAP definitions were used. In total, 71 patients were identified. 34/71 patients had pCR and were not included in further analysis. 37/71 patients had RD and HER2 was analyzed. 17/37 had HER2 loss and 20/37 remained HER2 positive. Mean follow-up time for HER2 loss was 43 months and 27 months for patients remaining HER2 positive, but neither group met 5-year Overall Survival as follow-up is ongoing. Recurrence Free Survival (RFS) was 35 months for HER2+ and 43 months for HER2 loss (P = 0.007). However, short follow-up time since diagnosis likely contributed to the underrepresentation of the true RFS of both groups. Therefore, at our institution, retained HER2 positivity on RD after NAC was associated with a statistically worse RFS. Although limited by sample size and follow-up time, further prospective investigation into the significance of HER2 discordance on RD assessed by 2018 definitions could clarify true RFS and if next-generation tumor profiling on RD will yield changes in tailored management.

13.
Med J Armed Forces India ; 79(4): 378-385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37441291

RESUMO

Background: Dental radiology represents the best model for evaluating the effects of low-dose ionizing radiation. Therefore, this study evaluated the awareness on radiation hygiene among dental ancillary personnel through a questionnaire and their absorbed doses by physical and biologic dosimetry. Methods: The multicentric study included two groups. Group I (N = 30) consisted of dental staff involved in dental radiology. An equal number of personnel who were not related to radiology formed the control group. Knowledge (K), attitude (A), and practice (P) of participants were assessed using a KAP questionnaire. Radiation exposure was evaluated by physical dosimetry at 3 time periods: at the beginning of the study (T1), after 10 months (T2), and at the end after 20 months (T3). Similarly, biologic dosimetry was also carried out at 3 time points by dicentric chromosome aberration assay. The data were compared using percentage analysis, analysis of variance (one-way analysis of variance), and Student's t- test. Results: The KAP survey demonstrated enhanced understanding of radiation protection measures and its sound practice by the participants. Physical dosimetry showed a significant increase in absorbed dose at 3 time points: T1, T2, and T3. However, no chromosomal aberrations were observed in blood lymphocytes for any of the participants in the optimized 4-day biodosimetry protocol. Conclusion: Good radiation protection protocols-safe distance from the radiation source and wear of lead aprons and thyroid collars-ensured low absorbed doses. The 4-day protocol is an important step toward developing biodosimetry laboratories in the Armed Forces Medical Services for clinical and national radiation countermeasure strategies.

14.
Opt Lett ; 48(14): 3753-3756, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37450742

RESUMO

The transfer function is the characteristic function of the dispersive element of a reconstructive spectrometer. It maps the transmitted spatial intensity profile to the incident spectral intensity profile of an input. Typically, a widely tunable and narrowband source is required to determine the transfer function across the entire operating wavelength range, which increases the developmental cost of these reconstructive spectrometers. In this Letter, we utilize the parabolic dispersion relation of a planar one-dimensional photonic crystal cavity, which acts as the dispersive element, to determine the entire transfer function of the spectrometer using measurements made at only two wavelengths. Using this approach, we demonstrate reliable reconstruction of input spectra in simulations, even in the presence of noise. The experimentally reconstructed spectra also follow the spectra measured using a commercial spectrometer.

15.
Molecules ; 28(10)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37241960

RESUMO

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a-d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2-22.2 µM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a-d against normal HEK-293 cells were in the range of 102.4-293.2 µM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 µM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a-d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis.


Assuntos
Antineoplásicos , Resistência a Múltiplos Medicamentos , Humanos , Células HEK293 , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Benzopiranos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga
16.
Indian J Otolaryngol Head Neck Surg ; 75(Suppl 1): 305-312, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37206818

RESUMO

The functional aspect of preservation of every healthy anatomical structure, particularly the ossicles, non-diseased mastoid cortex and middle ear mucosa, and to achieve this by transacanal endoscopic dual hand approach to middle ear, aditus and mastoid antrum with minimal posterior atticotomy and proximal aditotomy. The prospective study has been conducted over a period of 12 years from 2009 to 2021 in the Jorhat Medical College, Assam Medical College and Niramoy Hospital, Jorhat, Assam. Follow up was for a minimum of 4 years. The current study was a prospective hospital based study, carried out from May 1st, 2009 to April 30th, 2021 involving 157 subjects from 18 to 65 years with mean age of 38 + 2.5. Graft uptake rate of 93.6%. Minimal atticotomy with proximal aditotomy offers a clear view of the antrum with angled scopes of 30 degree and 45 degree and if any disease is located it can be removed through the transcanal approach with angled instruments and aditus patency can be confirmed by visual inspection. Hence, decreasing the need of unnecessary bone drilling as done with cortical mastoidectomy to create a parallel view.The endoscopic ear surgeries done with "dual hand endo-holder" were uneventful and much more comfortable as compared to the single hand technique. Functional approach by minimizing bone drilling, reestablishment of ventilation pathways and preservation of ossicles with disease clearance give better postoperative results in long term follow-up.

17.
J Clin Oncol ; 41(16): 3063-3071, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37075273

RESUMO

PURPOSE: To conduct an update of the ASCO venous thromboembolism (VTE) guideline. METHODS: After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022. RESULTS: Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding. RECOMMENDATIONS: Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.


Assuntos
Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Rivaroxabana/efeitos adversos , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia
18.
Nat Commun ; 14(1): 1680, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973261

RESUMO

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation of pre-metastatic cells, driven by actionable pathways including AXL and AURK. Blocking these two proteins blunts tumor invasion in patient-derived cultures. Furthermore, scRNAseq analyses of tumor-infiltrating CD8 + T-lymphocytes show two distinct trajectories to T-cell dysfunction, corroborated by their clonal architecture based on single-cell T-cell receptor sequencing. By determining key modulators of these trajectories, followed by validation using external datasets and functional experiments, we uncover a role for SOX4 in mediating T-cell exhaustion. Finally, interactome analyses between pre-metastatic tumor cells and CD8 + T-lymphocytes uncover a putative role for the Midkine pathway in immune-modulation and this is confirmed by scRNAseq of tumors from humanized mice. Aside from specific findings, this study demonstrates the importance of tumor heterogeneity analyses in identifying key vulnerabilities during early metastasis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Camundongos , Animais , Carcinoma de Células Escamosas/patologia , Evasão da Resposta Imune , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Linfócitos T CD8-Positivos , Linfócitos do Interstício Tumoral
19.
J Cardiovasc Electrophysiol ; 34(3): 738-747, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36640427

RESUMO

INTRODUCTION: Cardiac Implantable Electronic Devices (CIEDs) are widely used for the management of advanced heart failure and ventricular arrhythmias. CIED-Infection (CIED-I) has very high mortality, especially in the subsets of patients with limited health-care access and delayed presentation. The purpose of this study is to identify the risk-predictors mortality in subjects with CIED-I. METHODS: We performed a retrospective cohort study of a regional database in patients presenting with CIED infections to tertiary care medical centers across Western New York, USA from 2012 to 2020. The clinical outcomes included recurrent device infection (any admission for CIED-I after the first hospitalization for device infection), septic complications (pulmonary embolism, respiratory failure, septic shock, decompensated HF, acute kidney injury) and mortality outcomes (death during hospitalization, within 30 days from CIED-I, and within 1 year from CIED-I). We studied associations between categorical variables and hard outcomes using χ2 tests and used one-way analysis of variance to measure between-groups differences. RESULTS: We identified 296 patients with CIED-I, among which 218 (74%) were male, 237 (80%) were white and the mean age at the time of infection was 69.2 ± 13.7 years. One-third of the patients were referred from the regional facilities. Staphylococcus aureus was responsible for most infections, followed by Enterococcus fecalis. On multivariate analysis, the covariates associated with significantly increased mortality risk included referral from regional facility (OR: 2.0;1.0-4.0), hypertension (Odds ratio, OR: 3.2;1.3-8.8), right ventricular dysfunction (OR: 2.6;1.2-5.1), end-stage renal disease (OR: 2.6;1.1-6.2), immunosuppression (OR: 11.4;2.5-53.3), and septic shock as a complication of CIED-I (OR: 3.9;1.3-10.8). CONCLUSION: Hypertension, right ventricular dysfunction, immunosuppression, and end-stage renal disease are associated with higher mortality after CIED-I. Disproportionately higher mortality was also noted in subjects referred from the regional facilities. This underscores the importance of early clinical risk-assessment, and the need for a robust referral infrastructure to improve patient outcomes.


Assuntos
Desfibriladores Implantáveis , Cardiopatias , Falência Renal Crônica , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Choque Séptico , Disfunção Ventricular Direita , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Marca-Passo Artificial/efeitos adversos , Desfibriladores Implantáveis/efeitos adversos , Estudos Retrospectivos , Choque Séptico/complicações , Cardiopatias/etiologia , Fatores de Risco , Falência Renal Crônica/complicações , Infecções Relacionadas à Prótese/etiologia
20.
Indian J Community Med ; 48(6): 894-901, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38249711

RESUMO

Background: "CoviSainik Program" was implemented in collaboration with the Ambuja Cement Foundation and Community Medicine Department in rural districts of eight states of India from May to December 2021 to create a cadre of volunteers. The aim of the present paper is to describe the program and evaluate it so that the findings can be the guiding tool for policymakers to replicate a similar program. Material and Method: A cross-sectional, mixed-method - concurrent study design was adopted to evaluate the program for its short-term outcomes such as gain in the basic knowledge of COVID-19 amongst master trainers and their feedback and program output viz - the proportion of volunteers trained and their profile by census sampling. Motivational factors, experiences of volunteers, and outcomes of COVID-19 work in their villages were explored by purposive with maximum diversity sampling with 62 online in-depth interviews and 8 online focus group discussions (FGDs). Results: There was a statistically significant difference in the pre-test (12.8 ± 5.6) and post-test (25.9 ± 9.3) scores of the Master Training Program evaluation test. Out of 6534 trained volunteers, 5901 worked as volunteers, and amongst those, 47.1%, 35.1%, and 17.8% worked for ≤3 months, 3 to 6 months, and ≥6 months, respectively, in their villages. The major themes generated for motivational factors to join the program were altruism, savior nature, generating awareness, and concern for others. The major outcomes generated by trained volunteers COVID-19 vaccination were in raising awareness on COVID-19 appropriate behavior and early identification of COVID-19 cases in their villages. Conclusion: The "CoviSainik Program" was successful in creating cadres of trained volunteers.

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