RESUMO
To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , República Dominicana/epidemiologia , COVID-19/epidemiologia , Anticorpos Antivirais , Febre , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos NeutralizantesRESUMO
We report one- and 2-year results of a prospective, 5-year, multicenter study of radiographic, clinical, and patient-reported outcomes following triplanar first tarsometatarsal arthrodesis with early weightbearing. One-hundred and seventeen patients were included with a mean (95% confidence interval [CI]) follow-up time of 16.6 (15.5, 17.7) months. Mean (95% CI) time to weightbearing in a boot walker was 7.8 (6.6, 9.1) days, mean time to return to athletic shoes was 45.0 (43.5, 46.6) days, and mean time to return to unrestricted activity was 121.0 (114.5, 127.5) days. There was a significant improvement in radiographic measures with a mean corrective change of -18.0° (-19.6, -16.4) for hallux valgus angle, -8.3° (-8.9, -7.8) for intermetatarsal angle and -2.9 (-3.2, -2.7) for tibial sesamoid position at 12 months (n = 108). Additionally, there was a significant improvement in patient-reported outcomes (Visual Analog Scale, Manchester-Oxford Foot Questionnaire, and Patient-Reported Outcomes Measurement Information System) and changes were maintained at 12 and 24 months postoperatively. There was 1/117 (0.9%) reported recurrence of hallux valgus at 12 months. There were 16/117 (13.7%) subjects who experienced clinical complications of which 10/117 (8.5%) were related to hardware. Of the 7/117 (6.0%) who underwent reoperation, only 1/117 (0.9%) underwent surgery for a nonunion. The results of the interim report of this prospective, multicenter study demonstrate favorable clinical and radiographic improvement of the HV deformity, early return to weightbearing, low recurrence, and low rate of complications.
RESUMO
BACKGROUND: Robotic facelift thyroidectomy (RFT) was developed as a new surgical approach to the thyroid gland using a remote incision site. Early favorable results led to this confirmatory multi-institutional experience. METHODS: Prospectively collected data on consecutive patients undergoing RFT in five North American academic endocrine surgical practices were compiled. Surgical indications, operative times, final pathology, nodule size, complications, and postoperative management (drain use and length of hospital stay) were evaluated. RESULTS: A total of 102 RFT procedures were undertaken in 90 patients. All but one of the patients (98.9 %) were female, and the mean age was 41.9 ± 13.1 years (range 12-69 years). The indication for surgery was nodular disease in 91.2 % of cases; 8.8 % were completion procedures performed for a diagnosis of cancer. The mean size of the largest nodule was 1.9 cm (range 0-5.6 cm). The mean total operative time for a thyroid lobectomy was 162 min (range 82-265 min). No permanent complications occurred. There were 4 cases (3.9 %) of transient recurrent laryngeal nerve weakness, no cases of hypocalcemia, and 3 (2.9 %) hematomas. There were no conversions to an anterior cervical approach. The majority of patients were managed on an outpatient basis (61.8 %) and without a drain (65.7 %). CONCLUSIONS: RFT is technically feasible and safe in selected patients. RFT can continue to be offered to carefully selected patients as a way to avoid a visible cervical scar. Future prospective studies to compare this novel approach to other remote access approaches are warranted.
Assuntos
Procedimentos Cirúrgicos Robóticos/métodos , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Laryngeal nerve monitoring has been increasingly embraced as a mechanism for mitigating the risk of nerve damage during thyroid and parathyroid surgery. Vagal nerve monitoring has recently been introduced as a potentially increased level of nerve integrity scrutiny. We sought to define the risks and benefits of this technology in a prospective analysis of a series of patients undergoing neck endocrine surgery. SETTING: High-volume academic endocrine surgery practice. METHODS: A prospective, non-controlled trial of continuous vagal nerve monitoring (CVNM) in a projected cohort of 20 non-randomly selected patients undergoing thyroid and parathyroid surgery was planned. A commercially available nerve monitoring system with automatic periodic stimulation was utilized for both laryngeal nerve monitoring and CVNM. Demographic data were obtained, and outcome variables included surgical procedures performed, pathology, complications, incremental time required to achieve CVNM, and benefits of monitoring and stimulation. RESULTS: The patient accrual was aborted after 9 surgeries (12 nerves monitored) because of two serious adverse events (hemodynamic instability and reversible vagal neuropraxia attributable to the monitoring apparatus). No other complications occurred. The time to establish monitoring ranged from 3 to 26 min, with a median of 6 min (representing 2.9-12.2 % of the total surgical procedural time). The stimulation clamp became dislodged 11 times in 5 cases and was replaced in 7 of those instances. Benefits of CVNM included recognition of reduced amplitude and increased nerve latency in two patients. CONCLUSIONS: We report the first evidence that CVNM may cause serious patient harm. This novel approach is invasive and threatens patient safety. Although it may occasionally provide meaningful information, the risk-benefit ratio does not favor widespread adoption.
Assuntos
Monitorização Intraoperatória/efeitos adversos , Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Nervo Vago/fisiologia , Adulto , Bradicardia/etiologia , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Hipotensão/etiologia , Nervos Laríngeos/fisiologia , Monitorização Intraoperatória/métodos , Glândulas Paratireoides/cirurgia , Estudos ProspectivosRESUMO
OBJECTIVE: This study evaluated changes in thyroid compartment incision site locations with patient positioning to define a reliable method for placing the scar in the optimal vertical location. METHODS: The optimal incision location was marked with the patient sitting upright before surgery. The distance from the sternal notch to this mark was measured with the patient in the upright, supine, and final surgical positions. RESULTS: Complete data were available for 104 procedures. The mean distances from the sternal notch to the incision site were 4.8, 21.5, and 31.9 mm in the sitting, supine, and surgical positions, respectively. Each of these distances were significantly different from one another (P<.0001) and were independent of patient age, sex, body mass index (BMI), or height. CONCLUSIONS: Cutaneous cervical landmarks migrate significantly during patient positioning. Marking the thyroid compartment incision site while the patient is in an upright position results in a more predictable final scar location.
Assuntos
Glândula Tireoide/cirurgia , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Posicionamento do PacienteRESUMO
BACKGROUND: Though minimally invasive video-assisted thyroidectomy (MIVAT) offers many advantages over traditional thyroid surgery, its adoption in North America has been limited. This study analyzes the largest series of MIVAT in North America to explore its safety. METHODS: A prospectively maintained database of all patients undergoing thyroid surgery by a single surgeon from 2003 to 2011 at an academic tertiary care medical center was evaluated. Demographic information, surgical and pathologic data, and postoperative outcomes were analyzed. RESULTS: Beginning in 2005, a total of 260 MIVATs were performed during the study period. Outpatient surgery was accomplished in 234 MIVATs (90%). MIVAT patients were predominantly young (46.8±14.8 years vs 52.4±14.6 years for conventional thyroidectomy) and female (88.5% vs 75.5% for conventional thyroidectomy). There were no cases of permanent hypoparathyroidism or permanent recurrent laryngeal nerve dysfunction. Observed complications included transient recurrent laryngeal nerve dysfunction (n=10; 3.8%), cellulitis (n=1; 0.4%), and temporary hypocalcemia (n=6; 2.3%). The overall complication rate for MIVAT (6.5%) was lower than the overall complication rate in conventional thyroidectomy (18.5%, P<.0001). CONCLUSION: MIVAT can be performed safely with a low complication profile in a high-volume practice. The safety of MIVAT represented by this experience supports broader adoption across surgical practices.
Assuntos
Complicações Intraoperatórias/prevenção & controle , Procedimentos Cirúrgicos Robóticos , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia , Cirurgia Vídeoassistida , Adulto , Feminino , Humanos , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/prevenção & controle , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Avaliação de Resultados em Cuidados de Saúde , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Traumatismos do Nervo Laríngeo Recorrente/prevenção & controle , Reprodutibilidade dos Testes , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Tireoidectomia/estatística & dados numéricos , Estados Unidos , Cirurgia Vídeoassistida/efeitos adversos , Cirurgia Vídeoassistida/métodos , Cirurgia Vídeoassistida/estatística & dados numéricosRESUMO
Background: Proper hand hygiene (HH), which includes sanitizing with alcohol-based hand rub (ABHR) (or handwashing with soap and water if ABHR is unavailable), is key for preventing healthcare-associated infections (HCAI), including COVID-19. Understanding drivers of HH is key to improving adherence. Aim: This study aims to explore drivers and barriers to HH practice at two hospitals in the Dominican Republic in the context of the COVID-19 pandemic to inform development of HH behaviour change interventions. Methods: We conducted in-depth interviews with 20 hospital staff during September 2021. We used the COM-B (capability, opportunity, motivation, behaviour) model to explore HH experiences and preferences. Interviews were recorded, transcribed, coded, and analysed using a thematic approach. Results: A total of 11 parent codes and 27 sub-codes were identified, and 1145 coded segments were analysed. Use of handwashing with soap and water and/or sanitizing with ABHR was reported by all participants; handwashing was generally preferred. Participants expressed knowledge of proper HH methods (capability), but inconsistent supplies and lack of time presented HH challenges (opportunity). Interviewees described practicing HH to protect themselves and their families from COVID-19 and other infections (reflective motivation) or out of habit (automatic motivation). Discussion: By understanding and addressing underlying factors affecting HH, hospitals can decrease the risk of HCAIs. Our findings suggest that interventions implemented to improve HH in these hospitals should target motivation and opportunity. These findings informed a multimodal intervention to increase ABHR access and implement message-tested communications campaigns; end-point assessments will provide insights into the intervention's impact.
RESUMO
OBJECTIVE: This study investigates the role of trust in shaping COVID-19 vaccine acceptance in the Dominican Republic (DR) during the COVID-19 pandemic. DESIGN: Cross-sectional household survey. SETTING: Randomly selected households across 134 clusters in the DR, from 30 June 2021 to 12 October 2021. PARTICIPANTS: 5999 participants ≥16 years of age were enrolled. OUTCOME MEASURES: COVID-19 vaccine hesitancy (CVH) data were collected from participants ≥16 years of age and analysed as both an ordinal and binary variable. RESULTS: Overall, CVH was low (5.2% (95% CI 4.6% to 5.8%)), but more common among younger individuals, women and individuals of Mestizo ethnicity. Higher trust in local government, national government, scientists and local doctors (considered official sources) was associated with lower odds of CVH (OR 0.89 (95% CI 0.72 to 0.88), 0.89 (95% CI 0.81 to 0.98), 0.87 (95% CI 0.80 to 0.94) and 0.70 (95% CI 0.62 to 0.80), respectively). Higher trust in religious leaders, social media and traditional media (considered unofficial sources) was associated with higher odds of CVH, with respective ORs of 1.32 (95% CI 1.18 to 1.47), 1.30 (95% CI 1.19 to 1.41) and 1.08 (95% CI 0.97 to 1.22). CONCLUSION: We report findings on CVH from a national household survey in the DR and identify overall low rates of CVH but marked heterogeneity by age, gender and ethnicity. Trust in unofficial versus official sources of information is associated with increased CVH. These findings highlight and quantify the importance of trust as a key parameter when considering public health communication strategies.
Assuntos
Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Confiança , Hesitação Vacinal , Humanos , República Dominicana , Feminino , Masculino , Estudos Transversais , Adulto , COVID-19/prevenção & controle , COVID-19/epidemiologia , Pessoa de Meia-Idade , Vacinas contra COVID-19/administração & dosagem , Hesitação Vacinal/psicologia , Hesitação Vacinal/estatística & dados numéricos , Adulto Jovem , Adolescente , Idoso , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications. METHODS: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes. FINDINGS: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile. INTERPRETATION: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens. FUNDING: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL).
RESUMO
Chronically high levels of inorganic nutrients have been documented in Florida's coral reefs and are linked to increased prevalence and severity of coral bleaching and disease. Naturally disease-resistant genotypes of the staghorn coral Acropora cervicornis are rare, and it is unknown whether prolonged exposure to acute or chronic high nutrient levels will reduce the disease tolerance of these genotypes. Recently, the relative abundance of the bacterial genus Aquarickettsia was identified as a significant indicator of disease susceptibility in A. cervicornis, and the abundance of this bacterial species was previously found to increase under chronic and acute nutrient enrichment. We therefore examined the impact of common constituents of nutrient pollution (phosphate, nitrate, and ammonium) on microbial community structure in a disease-resistant genotype with naturally low abundances of Aquarickettsia. We found that although this putative parasite responded positively to nutrient enrichment in a disease-resistant host, relative abundances remained low (< 0.5%). Further, while microbial diversity was not altered significantly after 3 weeks of nutrient enrichment, 6 weeks of enrichment was sufficient to shift microbiome diversity and composition. Coral growth rates were also reduced by 6 weeks of nitrate treatment compared to untreated conditions. Together these data suggest that the microbiomes of disease-resistant A. cervicornis may be initially resistant to shifts in microbial community structure, but succumb to compositional and diversity alterations after more sustained environmental pressure. As the maintenance of disease-resistant genotypes is critical for coral population management and restoration, a complete understanding of how these genotypes respond to environmental stressors is necessary to predict their longevity.
Assuntos
Antozoários , Microbiota , Animais , Nitratos , Genótipo , Nutrientes , RickettsialesRESUMO
Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT80 for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.
RESUMO
Nutrient pollution is linked to coral disease susceptibility and severity, but the mechanism behind this effect remains underexplored. A recently identified bacterial species, 'Ca. Aquarickettsia rohweri,' is hypothesized to parasitize the Caribbean staghorn coral, Acropora cervicornis, leading to reduced coral growth and increased disease susceptibility. Aquarickettsia rohweri is hypothesized to assimilate host metabolites and ATP and was previously demonstrated to be highly nutrient-responsive. As nutrient enrichment is a pervasive issue in the Caribbean, this study examined the effects of common nutrient pollutants (nitrate, ammonium, and phosphate) on a disease-susceptible genotype of A. cervicornis. Microbial diversity was found to decline over the course of the experiment in phosphate-, nitrate-, and combined-treated samples, and quantitative PCR indicated that Aquarickettsia abundance increased significantly across all treatments. Only treatments amended with phosphate, however, exhibited a significant shift in Aquarickettsia abundance relative to other taxa. Furthermore, corals exposed to phosphate had significantly lower linear extension than untreated or nitrate-treated corals after 3 weeks of nutrient exposure. Together these data suggest that while experimental tank conditions, with an elevated nutrient regime associated with coastal waters, increased total bacterial abundance, only the addition of phosphate significantly altered the ratios of Aquarickettsia compared to other members of the microbiome.
Assuntos
Antozoários , Microbiota , Parasitos , Animais , Antozoários/microbiologia , Recifes de Corais , Genótipo , FosfatosRESUMO
Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. Funding: This study was funded by the US CDC.
RESUMO
Although somatic mutations influence the pathogenesis, phenotype, and outcome of myeloproliferative neoplasms (MPNs), little is known about their impact on molecular response to cytoreductive treatment. We performed targeted next-generation sequencing (NGS) on 202 pretreatment samples obtained from patients with MPN enrolled in the DALIAH trial (A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms; #NCT01387763), a randomized controlled phase 3 clinical trial, and 135 samples obtained after 24 months of therapy with recombinant interferon-alpha (IFNα) or hydroxyurea. The primary aim was to evaluate the association between complete clinicohematologic response (CHR) at 24 months and molecular response through sequential assessment of 120 genes using NGS. Among JAK2-mutated patients treated with IFNα, those with CHR had a greater reduction in the JAK2 variant allele frequency (median, 0.29 to 0.07; P < .0001) compared with those not achieving CHR (median, 0.27 to 0.14; P < .0001). In contrast, the CALR variant allele frequency did not significantly decline in those achieving CHR or in those not achieving CHR. Treatment-emergent mutations in DNMT3A were observed more commonly in patients treated with IFNα compared with hydroxyurea (P = .04). Furthermore, treatment-emergent DNMT3A mutations were significantly enriched in IFNα-treated patients not attaining CHR (P = .02). A mutation in TET2, DNMT3A, or ASXL1 was significantly associated with prior stroke (age-adjusted odds ratio, 5.29; 95% confidence interval, 1.59-17.54; P = .007), as was a mutation in TET2 alone (age-adjusted odds ratio, 3.03; 95% confidence interval, 1.03-9.01; P = .044). At 24 months, we found mutation-specific response patterns to IFNα: (1) JAK2- and CALR-mutated MPN exhibited distinct molecular responses; and (2) DNMT3A-mutated clones/subclones emerged on treatment.
Assuntos
Hidroxiureia , Transtornos Mieloproliferativos , Genômica , Humanos , Hidroxiureia/uso terapêutico , Interferon-alfa/uso terapêutico , Mutação , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genéticaRESUMO
The majority of JAK2V617F-negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin (CALR), resulting in a common carboxyl-terminal mutant fragment (CALRMUT), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALRMUT-specific T cells are rare in patients with CALRMUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALRMUT MPN from two independent cohorts. We observed that MHC-I alleles that present CALRMUT neoepitopes with high affinity are underrepresented in patients with CALRMUT MPN. We speculated that this was due to an increased chance of immune-mediated tumor rejection by individuals expressing one of these MHC-I alleles such that the disease never clinically manifested. As a consequence of this MHC-I allele restriction, we reasoned that patients with CALRMUT MPN would not efficiently respond to a CALRMUT fragment cancer vaccine but would when immunized with a modified CALRMUT heteroclitic peptide vaccine approach. We found that heteroclitic CALRMUT peptides specifically designed for the MHC-I alleles of patients with CALRMUT MPN efficiently elicited a CALRMUT cross-reactive CD8+ T cell response in human peripheral blood samples but not to the matched weakly immunogenic CALRMUT native peptides. We corroborated this effect in vivo in mice and observed that C57BL/6J mice can mount a CD8+ T cell response to the CALRMUT fragment upon immunization with a CALRMUT heteroclitic, but not native, peptide. Together, our data emphasize the therapeutic potential of heteroclitic peptide-based cancer vaccines in patients with CALRMUT MPN.
Assuntos
Vacinas Anticâncer , Transtornos Mieloproliferativos , Neoplasias , Animais , Calreticulina/genética , Humanos , Janus Quinase 2/genética , Complexo Principal de Histocompatibilidade , Camundongos , Camundongos Endogâmicos C57BL , Mutação/genética , Transtornos Mieloproliferativos/genética , Neoplasias/genética , Peptídeos , Vacinas de Subunidades AntigênicasRESUMO
OBJECTIVE: To review the types, content and accuracy of print media reports on male circumcision for preventing HIV infection among men in sub-Saharan Africa. METHODS: We conducted a trilingual search (English, French, Portuguese) of LexisNexis(R) with the phrase 'male circumcision' for the period from 28 March 2007 to 30 June 2008. The articles identified were screened for the central theme of male circumcision for preventing HIV infection in men in sub-Saharan Africa and for publication types targeting lay audiences - newspapers, magazines, newswires or newsletters. We judged the accuracy of the reports and determined the context, public perceptions, misconceptions and areas of missing information in the print media. We also explored whether the media could be better used to maximize the impact of male circumcision. FINDINGS: We identified 412 articles, of which 219 were unique and 193 were repeats. 'Peaks and valleys' occurred in the volume of articles over time. Most articles (56.0%) presented male circumcision for the prevention of HIV infection in a positive light. Those that portrayed it negatively had an overall repeat rate 2.9 times higher than positive articles. Public health messages formulated by international health agencies were few but generally accurate. CONCLUSION: The accuracy of the reports was good, although the articles were few and frequently omitted important messages. This suggests that public health authorities must help the media understand important issues. A communication strategy to sequence important themes as male circumcision programmes are scaled up would allow strategic coverage of accurate messages over time.
Assuntos
Circuncisão Masculina , Infecções por HIV/prevenção & controle , Meios de Comunicação de Massa , África Subsaariana , Bibliometria , Humanos , MasculinoRESUMO
BACKGROUND: Lymphatic malformations are benign but potentially life-threatening lesions mostly found in the head and neck. They can be classified into two types: microcystic and macrocystic. Microcystic lesions are more difficult to treat. In this study, we describe the histologic features and expression of lymphatic endothelial markers in microcystic and macrocystic lymphatic malformations and correlate clinical data with histologic and immunohistochemical data. METHODS AND RESULTS: This is a retrospective study of clinical data and tissue specimens which were collected from 18 children who underwent surgical excision of lymphatic malformations. The clinical data were analyzed with descriptive statistics. Microcystic and macrocystic lesion specimens were examined with Movat pentachromic stain and immunohistochemistry for lymphatic endothelial markers. Patients with microcystic lesions were more likely to have mucosal involvement, recurrence, and higher stages of disease, compared with those with macrocystic lesions. Microcystic and macrocystic lesions stained similarly with Movat pentachromic stain and for lymphatic endothelial cell markers. CONCLUSIONS: Although microcystic and macrocystic lesions have different clinical behavior, they have indistinguishable histological features and immunohistochemical staining for markers of lymphatic endothelium. These findings suggest that both microcystic and macrocystic lesions are derived from similar tissue but may behave differently based on their anatomic microenvironment.
Assuntos
Biomarcadores Tumorais/análise , Endotélio Linfático/patologia , Neoplasias de Cabeça e Pescoço/patologia , Linfangioma Cístico/patologia , Adolescente , Criança , Pré-Escolar , Endotélio Linfático/química , Feminino , Neoplasias de Cabeça e Pescoço/química , Humanos , Técnicas Imunoenzimáticas , Lactente , Linfangioma Cístico/química , Masculino , Estudos Retrospectivos , Coloração e Rotulagem/métodosRESUMO
OBJECTIVE: The purpose of this study was to evaluate changes in airway infantile hemangioma treatment. STUDY DESIGN: Retrospective. SUBJECTS: Airway hemangioma patients, tertiary pediatric hospital. METHODS: Data collected included age at diagnosis, evaluation methods, hospitalizations, airway size, and interventions. Patients were divided into group A (1981-1993) and group B (1994-2005) and were analyzed using descriptive statistics, the Fisher exact test, and the Student t test. RESULTS: Thirty-two subjects were identified. Nasopharyngoscopy was used more in group B (11/16 [69%]) than group A (4/16 [25%], P=0.032). CT angiography (3/16 [19%]) and laryngeal distractors (11/16 [69%]) were only used in group B; these techniques showed airway hemangiomas to be "transglottic," not just "subglottic." Intralesional steroids alone (3/16 [19%]) and primary hemangioma excision (2/16 [13%]) were new treatments used in group B. Frequent direct laryngoscopies (>six) correlated with tracheotomy (5/32 [16%], P=0.015). Presenting age (<2 months) impacted treatment more than airway hemangioma size. CONCLUSIONS: New methods of airway infantile hemangioma assessment changed our concept of airway hemangiomas and their primary treatment.
Assuntos
Glucocorticoides/uso terapêutico , Hemangioma/tratamento farmacológico , Hemangioma/cirurgia , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/cirurgia , Laringectomia/métodos , Laringoscopia/métodos , Feminino , Glote/cirurgia , Glucocorticoides/administração & dosagem , Hemangioma/diagnóstico , Hospitais Universitários , Humanos , Lactente , Injeções Intralesionais , Neoplasias Laríngeas/diagnóstico , Masculino , Prontuários Médicos , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: We sought to evaluate the relationship between the preoperative core-laboratory parathyroid hormone (CL-PTH) level and the baseline intraoperative PTH (IOPTH) level and assess the impact of any differences on clinical decision making in consecutive surgical patients with primary hyperparathyroidism undergoing parathyroidectomy. METHODS: The CL-PTH and baseline IOPTH levels were compared. The influence of relying on either the CL-PTH or baseline PTH levels for intraoperative decision making was determined. RESULTS: Data were available for 316 patients. Baseline IOPTH measurements were usually higher than the CL-PTH (247 patients; 78.2%) measurements, with a mean difference of 68.2 pg/mL (P < .001). Using the CL-PTH as a surrogate for the baseline parathyroid hormone (PTH) would have prolonged the operation in 23 patients (7.3%). CONCLUSION: Baseline point-of-care IOPTH levels were higher than the preoperative CL-PTH levels in >75% of patients undergoing parathyroidectomy. Using the CL-PTH in lieu of an IOPTH baseline value would prolong the operation in some patients.