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Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal neurodegenerative disorder caused by prion proteins. In about 85% of patients, CJD occurs as a sporadic disease with no recognizable pattern of transmission. Sporadic CJD (sCJD) can present with rapid cognitive and functional decline, memory deficits, myoclonus, pyramidal and extrapyramidal signs, and visual deficits. The large spectrum of phenotypic variability has made the recognition of prion diseases difficult, and given the rare incidence, it is not uncommon for it to be missed as a potential diagnosis. We present a highly unusual case of a 76-year-old woman with rapidly progressive sCJD who died within five weeks of presentation. Our case demonstrates a typical sequence of symptoms, with rapidly progressive dementia and cerebellar signs at disease onset and myoclonus later in the disease course.
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Pembrolizumab is a programmed cell death receptor-1 (PD-1) blocking immune checkpoint inhibitor (ICI) that is a mainstay of cancer treatment. Pembrolizumab has a lower incidence of colitis and diarrhea compared to other ICIs. The current study presents the case of a 30-year-old female patient on pembrolizumab with stage IV colon cancer who presented with diarrhea (50 times a day) and symptoms of colitis. A computed tomography scan of the abdomen and pelvis suggested proctitis. Stool studies were negative for enteric pathogens, but stool white blood cell (WBC) was positive, and calprotectin was >10,000 ug/g. A colonoscopy showed pancolitis with small internal hemorrhoids. Histopathology showed cryptitis and crypt abscesses with mild focal architectural distortion, mucosal erosion/ulcer, and focal crypt atrophy from the cecum to the rectum. All ICIs were discontinued, and the patient was initially managed with IV fluids. The patient was subsequently started on methylprednisolone and loperamide after colonoscopy. The number of bowel movements decreased to six per day after the above management. The patient was then switched to oral prednisone and discharged with outpatient follow-up. This case reveals the importance of assessing immune-related adverse effects (irAEs) even though incidence rates associated with a specific ICI might be low.
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Left ventricular pseudoaneurysm is a ventricular free wall rupture contained within the adjacent adherent pericardium or scar tissue. Myocardial infarction (MI), cardiac surgery, and chest trauma are the common causes. The most common presenting symptoms of pseudoaneurysms are congestive heart failure, chest pain, and dyspnea, but a small percentage of patients may be asymptomatic. Early diagnosis and treatment are of prime importance because of the tendency of pseudoaneurysms to expand and rupture, with a high mortality rate, especially if left untreated. We present a case of a 65-year-old man who was found to have left ventricular pseudoaneurysm on a follow-up echocardiography within three weeks of an MI. He subsequently underwent patch repair and was discharged after medical optimization. Our case highlights the importance of maintaining a high clinical suspicion of pseudoaneurysm in a patient post-MI, as delayed diagnosis and treatment can be fatal.
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CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158-66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αß signatures. Suboptimal TCRαß signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections.
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Linfocitos T CD8-positivos , Longevidad , Recién Nacido , Humanos , Anciano , Epítopos de Linfocito T/genética , Linfocitos T Citotóxicos , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T/genéticaRESUMEN
BACKGROUND: Residual/reconverted red bone marrow (RBM) in adult knees is occasionally observed on routine knee magnetic resonance imaging (MRI). We aimed to identify its prevalence, distribution, and associations with lifestyle factors, knee structural abnormalities, and knee symptoms in young adults. METHODS: Participants (n = 327; aged = 31-41 years) were selected from the Childhood Determinants of Adult Health (CDAH) knee study. They underwent T1-weighted and proton-density-weighted fat-suppressed MRI scans of knees. Residual/reconverted RBM in distal femur and proximal tibia were graded semi-quantitatively (grades: 0-3) based on the percentage area occupied. Knee structural abnormalities were graded semi-quantitatively using previously published MRI scoring systems. Knee symptoms (pain, stiffness, and dysfunction) were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale during CDAH knee study (year: 2008-2010) and at 6-9-year follow-up during the CDAH-3 study (year: 2014-2019). Associations between definite RBM (grade ≥ 2) and lifestyle factors, knee symptoms, and structural abnormalities were described using log-binomial regressions. RESULTS: Definite RBM was seen in females only, in 29 out of 154 cases (18.8%), with femoral involvement preceding tibial involvement. Definite RBM was associated with increased BMI (PR = 1.09/kg/m2; 95% CI: 1.03, 1.16), overweight status (PR = 2.19; 95% CI: 1.07, 4.51), and WOMAC knee pain (PR = 1.75; 95% CI: 1.11, 2.74) in cross-section analysis. However, there was no association between RBM and knee-pain after seven years (PR = 1.15; 95% CI: 0.66, 2.00). There were no associations between RBM and knee structural abnormalities. CONCLUSION: Presence of definite RBM in young adult knees was observed in females only. Definite RBM was associated with overweight measures, and the modest association with knee pain may not be causally related.
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Background: Residents of nursing homes are among the most vulnerable to COVID-19. There is no standardized approach for integration with hospitals for outbreak response. Previously, we described collaboration between a hospital and regional facilities. As a component of our COVID-19 Outbreak Response, we describe the impact of virtual daily rounds as an efficient and effective tool for facility outbreak in Central Virginia. Methods: At this facility, 82 (60%) residents were infected. Our team rapidly deployed technology to support staff at the facility. Virtual daily rounds created a systematic approach for patient care. The goals of virtual daily rounds include (1) efficiently facilitating HIPAA-compliant communication between nursing and all licensed independent providers, (2) rapid identification of clinical decline, (3) facilitation of care escalation, (4) facilitating bidirectional transfers, and (5) rapid and efficient identification of patients appropriate for telemedicine pulmonary consultation. Results: The outbreak remained active 6 weeks; 82 of 136 (60%) residents were infected, and 36 (44%) COVID-19 positive residents were seen by telemedicine consultation. Fifty-seven (70%) residents remained in-facility for treatment. Twenty-one residents died (15%); 10 in facility, 11 in hospital. Of those seen in telemedicine consultation, 24 (69%) remained on the treat-in-place protocol with goal-concordant care. These hospitalization and mortality rates are significantly lower than similar outbreaks reported. Discussion and Conclusion: We have since instituted this system at seven other facilities. A model of virtual daily rounding holds promise for decreasing mortality/hospitalization in this vulnerable population through systematically identifying patients most appropriate for telemedicine and cultivating close collaboration between hospitals and nursing homes.
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COVID-19 , Telemedicina , Brotes de Enfermedades , Hospitales , Humanos , SARS-CoV-2RESUMEN
More than 122 million cases of COVID-19 infection have been documented, and hundreds of thousands are being added every day. Several co-morbidities are associated with COVID-19, among which hypercoagulability has garnered the attention of many doctors and researchers. Most cases of vascular thrombosis are noted in intensive care unit (ICU) patients with serious disease; among these, many cases of deep venous thrombosis and pulmonary embolism have been noted. A few cases of portal vein thrombosis have also been documented in ICU patients with severe COVID-19. Here, we present a case of a portal vein and superior mesenteric vein thrombosis in a patient with subclinical COVID-19 infection. Through this case report, we intend to increase the research horizon and wish to help diagnose co-morbidities associated with COVID-19 at an earlier stage.
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To better understand primary and recall T cell responses during coronavirus disease 2019 (COVID-19), it is important to examine unmanipulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells. By using peptide-human leukocyte antigen (HLA) tetramers for direct ex vivo analysis, we characterized CD8+ T cells specific for SARS-CoV-2 epitopes in COVID-19 patients and unexposed individuals. Unlike CD8+ T cells directed toward subdominant epitopes (B7/N257, A2/S269, and A24/S1,208) CD8+ T cells specific for the immunodominant B7/N105 epitope were detected at high frequencies in pre-pandemic samples and at increased frequencies during acute COVID-19 and convalescence. SARS-CoV-2-specific CD8+ T cells in pre-pandemic samples from children, adults, and elderly individuals predominantly displayed a naive phenotype, indicating a lack of previous cross-reactive exposures. T cell receptor (TCR) analyses revealed diverse TCRαß repertoires and promiscuous αß-TCR pairing within B7/N105+CD8+ T cells. Our study demonstrates high naive precursor frequency and TCRαß diversity within immunodominant B7/N105-specific CD8+ T cells and provides insight into SARS-CoV-2-specific T cell origins and subsequent responses.
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Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Epítopos Inmunodominantes/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Secuencias de Aminoácidos , Linfocitos T CD4-Positivos , Niño , Convalecencia , Proteínas de la Nucleocápside de Coronavirus/química , Epítopos de Linfocito T/química , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Epítopos Inmunodominantes/química , Masculino , Persona de Mediana Edad , Fenotipo , Fosfoproteínas/química , Fosfoproteínas/inmunología , Receptores de Antígenos de Linfocitos T/química , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T alfa-beta/química , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
Purpose: The vulnerability of postacute and long-term care (PA/LTC) facility residents to COVID-19 has manifested across the world with increasing facility outbreaks associated with high hospitalization and mortality rates. Systematic protocols to guide telehealth-centered interventions in response to COVID-19 outbreaks have yet to be delineated. This article is intended to inform PA/LTC facilities and neighboring health care partners how to collaboratively utilize telehealth-centered strategies to improve outcomes in facility outbreaks. Methods: The University of Virginia rapidly developed a multidisciplinary telehealth-centered COVID-19 facility outbreak strategy in response to a LTC facility outbreak in which 41 (out of 48) facility residents and 7 staff members tested positive. This strategy focused on supporting the facility team remotely using rapidly deployed technologic solutions. Goals included (1) early identification of patients who need their care escalated, (2) monitoring and treating patients deemed safe to remain in the facility, (3) care coordination to facilitate bidirectional transfers between the skilled nursing facility (SNF) and hospital, and (4) daily facility needs assessment related to technology, infection control, and staff well-being. To achieve these goals, a standardized approach centered on daily multidisciplinary virtual rounds and telemedicine consultation was provided. Results: Over a month since the outbreak began, 18 out of 48 (38%) facility residents required hospitalization and 6 (12.5%) died. Eleven facility residents have since returned back to the SNF after recovering from their hospitalization. No staff required hospitalization. Conclusions: Interventions that reduce hospitalizations and mortality are a critical need during the COVID-19 pandemic. The mortality and hospitalization rates seen in this PA/LTC facility outbreak are significantly lower than has been documented in other facility outbreaks. Our multidisciplinary approach centered on telemedicine should be considered as other PA/LTC facilities partner with neighboring health care systems in responding to COVID-19 outbreaks. We have begun replicating these services to additional PA/LTC facilities facing COVID-19 outbreaks.
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COVID-19/epidemiología , Consulta Remota/organización & administración , Instituciones Residenciales/organización & administración , Atención Subaguda/organización & administración , Continuidad de la Atención al Paciente , Humanos , Control de Infecciones/organización & administración , Evaluación de Necesidades/organización & administración , Pandemias , SARS-CoV-2 , Factores de TiempoRESUMEN
Extra renal angiomyolipoma is an exceedingly rare entity. This is usually not associated with tuberous sclerosis as it has no human melanoma black 45 immune reactive cells although it shares the terminology with renal angiomyolipoma. The histological features are characterized by admixture of blood vessels, smooth muscles, and mature adipose tissues in variable proportion. Surgical excision is considered curative. We report a case of isolated vulval angiomyolipoma in a 45-year-old female which clinically and radiologically presented as lipoma like lesion. Our case of isolated vulval angiomyolipoma is the first reported case in the literature.
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Angiomiolipoma/diagnóstico por imagen , Neoplasias de la Vulva/diagnóstico por imagen , Angiomiolipoma/cirugía , Femenino , Humanos , Persona de Mediana Edad , Ultrasonografía , Neoplasias de la Vulva/cirugíaRESUMEN
An osseous metaplasia is a phenomenon which has been described in a wide variety of tissue types with respect to both neoplastic and non-neoplastic conditions. However, an osseous metaplasia is exceedingly rare in colonic polyps. We are herein representing a case of osseous metaplasia in a juvenile rectal polyp in a six year old boy, with review of the literature on the suggested mechanisms of its aetiology.
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BACKGROUND: Substance users approach a treatment facility for a variety of reasons as well as avoid or delay in help seeking due to perceived fears with treatment facilities. Sometimes these factors might be associated with treatment outcomes. OBJECTIVES: We studied the relationship of reasons and fears of treatment seeking with treatment outcome in substance users. MATERIALS AND METHODS: One hundred subjects, attending the Drug Deaddiction and Treatment Centre, PGIMER, were prospectively recruited by purposive sampling. A semistructured proforma was used to gather sociodemographic and clinical data. Reasons of help-seeking and fear questionnaire, social support scale, and PGI locus of control scale were then applied. Followup data were available for 69 patients, which were classified into good or poor outcome based on relapse status. RESULTS: At 6 months followup, 22 patients had relapsed, while 47 patients did not relapse. A higher degree of dysfunction due to substance at baseline was associated with relapsed status at followup. Parents or guardians coming to know about resuming substance and being unemployed for a long time were the reasons associated with relapsed status, while needing to consult a doctor immediately was significantly related to abstinent status at followup. Fear of not being able to meet substance using friends was associated with a poorer outcome in the form of relapse. CONCLUSIONS: Reasons for treatment seeking as well as fears related to treatment have significant implications on the clinical outcome of substance abusing patients. Addressing these could help in better patient outcomes.
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AIMS: To describe the public use of respiratory hygiene behaviours during the 2009 influenza pandemic and to test the feasibility of an observational method. METHODS: Respiratory behaviour was systematically observed at three public settings during August 2009 in the capital city of New Zealand (Wellington). Data on each coughing or sneezing event were collected. RESULTS: A total of 384 respiratory events were observed, at a rate of 0·8 cough/sneeze per observed-person-hour. Around a quarter of respiratory events (27·3%) were uncovered, and there was infrequent use of the responses recommended by health authorities (i.e., covering with a tissue or handkerchief at 3·4% and covering with elbow or arm at 1·3%). Respiratory event rates were higher in all settings that were 'high flow' (for people movement) compared to 'low flow' settings. Uncovered events were more common among people at the hospital entrance versus the hospital café [risk ratio (RR) = 7·8, 95% confidence interval (CI): 1·1-52·6] and when a person was located within 1 m of others (RR = 1·5, 95% CI: 1·1-1·9). Observing respiratory hygiene was found to be feasible in all of the selected public locations. There was good agreement between observing pairs about whether or not respiratory events occurred (inter-observer correlation = 0·81) and for uncovered versus covered events (total Cohen's kappa score = 0·70). CONCLUSIONS: It was feasible to document respiratory hygiene behaviour in public urban settings during a influenza pandemic. Respiratory hygiene advice was not being adequately followed by this population towards the end of the first wave of the pandemic.