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BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to improved outcomes for many cancer types. However, their use can also precipitate immune-related adverse events (irAEs) that can affect any organ system. While irAEs are often mild, they rarely affect multiple organ systems concurrently and can be fatal. CASE: We report a fatal case of myasthenia gravis, myositis, and cardiotoxicity overlap syndrome precipitated by the ICI pembrolizumab along with a brief review of available literature. CONCLUSION: Early recognition of high grade irAEs and prompt intervention is essential. Despite the poor prognosis of these overlap syndromes, current recommendations offer little guidance for severe cases and warrant a call for increased awareness and expansion of available therapeutics.
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Anticorpos Monoclonais Humanizados , Inibidores de Checkpoint Imunológico , Miastenia Gravis , Miosite , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/imunologia , Miosite/patologia , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Evolução Fatal , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Masculino , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologiaRESUMO
OBJECTIVES: The purpose of this study was to identify the most parsimonious combination of cognitive tests that accurately predicts the likelihood of passing an on-road driving evaluation in order to develop a screening measure that can be administered as an in-office test. DESIGN: This was a psychometric study of the new test's diagnostic accuracy. SETTINGS AND PARTICIPANTS: The study was conducted at the Florida Atlantic University's Memory Center and Clinical Research Unit, both easily accessible to older drivers. Participants were older drivers who received a driving evaluation at the Memory Center and agreed to have their results included in the Driving Repository and community-based older drivers who volunteered to participate. METHODS: Mini-Mental State Exam (MMSE), Trail Making Tests A and B, Clock Test, Hopkins Verbal Learning Test, and Driving Health Inventory results were compared with an on-road driving evaluation to identify those tests that best predict the ability to pass the on-road evaluation. RESULTS: Altogether, 412 older drivers, 179 men and 233 women, were included in the analysis. Fifty-four percent of Driving Repository participants failed the on-road evaluation compared with 8% of the community sample. The highest correlation to the on-road evaluation was Trails B time in seconds r = -0.713 (P < .001). Variables with high multicollinearity and/or low correlation with the on-road evaluation were eliminated and sets of receiver operating characteristics curves were generated to assess the predictive accuracy of the remaining tests. A linear combination of Trails B in seconds and MMSE using the highest of the Serial 7s or WORLD spelled backward scores accounted for the highest area under the curve of 0.915. Finally, an algorithm was created to rapidly generate the prediction for an individual patient. CONCLUSIONS AND IMPLICATIONS: The Fit2Drive algorithm demonstrated a strong 91.5% predictive accuracy. Usefulness in office-based patient consultations is promising but remains to be rigorously tested.
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Condução de Veículo , Psicometria , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Programas de Rastreamento/métodos , Florida , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Exame para Habilitação de MotoristasRESUMO
PURPOSE: High-dose methotrexate (HDMTX) is an antineoplastic dosing strategy used to treat various cancers including primary central nervous system lymphoma. Trimethoprim-sulfamethoxazole (TMP/SMX) is commonly used for antibiotic prophylaxis against Pneumocystis pneumonia infections in this patient population. Significant drug-drug interactions between TMP/SMX and methotrexate (MTX) leading to adverse outcomes have been documented, primarily in adult patients taking MTX for rheumatologic conditions. METHODS: This study is a single-center, retrospective, cohort study comparing outcomes in patients where TMP/SMX was held during HDMTX and patients who received concurrent prophylactic TMP/SMX during treatment. The primary end point was mean MTX level at 24, 48, and 72 hours. Secondary end points included rate of nonhematologic toxicity, rate of hematologic toxicity, median days to MTX clearance, and frequency of glucarpidase utilization. RESULTS: In total, 248 cycles of HDMTX were analyzed from 221 individual patients. One hundred ninety-one cycles were administered without prophylactic TMP/SMX, and 57 were administered with TMP/SMX. The median MTX level at 24, 48, and 72 hours in those without versus with prophylactic TMP/SMX was 4.30 versus 4.30, 0.29 versus 0.30, and 0.14 versus 0.15, respectively. Similarly, rates of hematologic and nonhematologic toxicities did not differ significantly between groups with the exception of neutropenia; however, there was no corresponding increased rate of neutropenic fever. Only one patient received glucarpidase and had not received TMP/SMX. CONCLUSION: Prophylactic TMP/SMX had minimal interaction with HDMTX and does not lead to increased time to clearance or clinically relevant toxicities. Prophylactic TMP/SMX can be safely administered with HDMTX in adult patients.
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Interações Medicamentosas , Metotrexato , Combinação Trimetoprima e Sulfametoxazol , Humanos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Metotrexato/administração & dosagem , Estudos Retrospectivos , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
BACKGROUND: Juvenile Nasopharyngeal Angiofibroma (JNA) is a fibrovascular tumor of the nasopharynx that classically presents in adolescent males. The reported mean age of onset is between 13 and 22 years old [1-6]. Significant androgen stimulation is hypothesized to explain the strong predisposition for JNA to present in young adolescent males. However, considerable variability in age at diagnosis exists with rare involvement of very young patients incongruent with typical male pubertal growth patterns. OBJECTIVE: The purpose of this systematic review is to identify cases of early-onset JNA (EOJNA), (defined as age < 10 years) in the literature and to examine the disease characteristics and treatments used in this patient group. A case of a 7 year old boy with EOJNA at our institution is also described and presented. METHODS: We searched Embase, Cochrane database and MEDLINE from 1996 to February 2021 for studies that reported cases of EOJNA. Relevant clinico-demographic data, disease severity and treatment outcomes were recorded and analyzed using descriptive statistics. We compared our findings with reported means for JNA in all ages. RESULTS: We identified 29 studies containing a total of 34 cases of EOJNA. The vast majority (31/34) of patients were males and the mean age of diagnosis was 8.15 years old. The most common presenting symptoms were nasal obstruction (65.2%) and epistaxis (60.9%). Patients were most commonly Radkowski stage II (39.4%) and III (39.4%). Primary treatment modalities included open surgery (66.7%), endoscopic surgery (24.2%), and radiotherapy (9.1%). Recurrence was evident in 30%. Radkowski stage and type of treatment did not differ significantly within the EOJNA group (p = 0.440 and p = 0.659, respectively). CONCLUSION: This systematic review suggests that rare cases of EOJNA have distinct disease characteristics. Patients in this cohort appeared to have more advanced disease and higher recurrence rates when compared with reported averages. We hope that this review prompts increased clinical awareness of this potentially more aggressive subtype of JNA. As more cases of EOJNA are reported, a more powered statistical analysis of this cohort would be feasible.
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Angiofibroma , Obstrução Nasal , Neoplasias Nasofaríngeas , Adolescente , Humanos , Masculino , Adulto Jovem , Adulto , Criança , Feminino , Angiofibroma/diagnóstico , Angiofibroma/cirurgia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirurgia , Epistaxe , Resultado do Tratamento , Obstrução Nasal/etiologia , Estudos RetrospectivosAssuntos
Linfoma de Célula do Manto , Adulto , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/terapia , Linfoma de Célula do Manto/patologia , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Antígenos CD19 , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologiaRESUMO
The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups.
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Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Humanos , Estudos Retrospectivos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Sulfonamidas , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/uso terapêuticoRESUMO
Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8+ T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8+ T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor-exhausted T cells. This reversal was enhanced by combined BETi and anti-PD1 treatment. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increase in expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8+ T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8+ T cells and maintaining a pool of anti-PD1 responsive CD8+ T cells.
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Linfócitos T CD8-Positivos , Leucemia Mieloide Aguda , Animais , Camundongos , Leucemia Mieloide Aguda/metabolismo , Linfócitos T ReguladoresRESUMO
Marine heatwaves (MHWs)-extremely warm, persistent sea surface temperature (SST) anomalies causing substantial ecological and economic consequences-have increased worldwide in recent decades. Concurrent increases in global temperatures suggest that climate change impacted MHW occurrences, beyond random changes arising from natural internal variability. Moreover, the long-term SST warming trend was not constant but instead had more rapid warming in recent decades. Here we show that this nonlinear trend can-on its own-appear to increase SST variance and hence MHW frequency. Using a Linear Inverse Model to separate climate change contributions to SST means and internal variability, both in observations and CMIP6 historical simulations, we find that most MHW increases resulted from regional mean climate trends that alone increased the probability of SSTs exceeding a MHW threshold. Our results suggest the need to carefully attribute global warming-induced changes in climate extremes, which may not always reflect underlying changes in variability.
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Mudança Climática , Aquecimento Global , Temperatura , Modelos Lineares , Oceanos e MaresRESUMO
The bladder is both an intraperitoneal and extraperitoneal structure. Its anatomical position increases its risk of rupture. The resultant urine leak or extravasation can be intraperitoneal, extraperitoneal, or even both-with the former leading to more sinister outcomes. Intraperitoneal bladder rupture can lead to urinary ascites which along with anuria and abdominal pain, can present with an apparent abrupt decline in renal function as the creatinine-rich products diffuse across the peritoneal membrane. Glomerular filtration rate, a measure of kidney function is related to the levels of serum creatinine. Clinicians can therefore misdiagnose their patient with acute kidney injury when the serum creatinine is elevated as a consequence of urine being present in the peritoneal space. This is a case report of a 62-year-old male with pseudo-renal failure following intraperitoneal bladder rupture after a fall face-forwards three hours previously. The fall was due to icy conditions outside and no preceding symptoms were reported. He presented to the Accident and Emergency department with abdominal pain and no other positive symptoms. The patient had a good World Health Organisation (WHO) performance status with a background of hypertension, diabetes, and hypercholesterolemia. The bedside examination of the patient revealed a distended, abdomen with peritonitis. There were no signs of urogenital trauma. Blood testing revealed a low estimated glomerular filtration rate (eGFR) and raised creatinine (eGFR of 7 millilitres/minute and creatinine of 658 micromoles/litre). Computerised tomography examination of the abdomen and pelvis (CTAP) revealed free fluid within the peritoneal cavity and an irregular bladder wall. A CT cystogram and consultation with urology led to the diagnosis of intraperitoneal bladder rupture. The patient's renal function from an initial set of blood tests was reduced. This was not a true impairment in renal function but rather a complication secondary to extravasation of urine in the intraperitoneal space, ie., pseudo renal failure. This supposed impairment in renal function had numerous implications. It affected the choice of antibiotics; amoxicillin and gentamicin were given at a reduced dose due to the patient's renal function and the patient was prepared for operation theatre. The patient's blood creatinine was falsely elevated at 658 micromoles/litre due to the diffusion of creatinine from the free urine in the peritoneal space into the blood. This painted a false image of renal failure and protracted the clinical decision-making process. Relatively simple measures like an ascitic tap could have helped to differentiate this from a true acute kidney injury and could have resulted in quicker and more effective treatment of this patient. The patient went on to have bladder repair under urology. His follow-up cystogram four weeks post-operation did not show any leak.
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Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here, we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.
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Regulação do Apetite , Apetite , Animais , Hormônio Liberador da Corticotropina/metabolismo , Ingestão de Alimentos/fisiologia , Camundongos , Neurônios/fisiologia , OptogenéticaRESUMO
Acute promyelocytic leukemia (APL) is a rare acute leukemia generally considered curable with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Some patients have co-morbidities that may limit the use of these agents and therefore impact curability. Adverse effects of ATO include life-threatening electrocardiographic abnormalities. ATO and its metabolites are partially excreted in the urine, and it is unclear to what extent ATO pharmacokinetics are impacted by hemodialysis. We present a patient on chronic hemodialysis successfully treated with ATO and ATRA for newly diagnosed APL. Complete molecular remission was achieved after induction and several drug-related toxicities were managed.
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The discovery of more than 4500 extrasolar planets has created a need for modeling their interior structure and dynamics. Given the prominence of iron in planetary interiors, we require accurate and precise physical properties at extreme pressure and temperature. A first-order property of iron is its melting point, which is still debated for the conditions of Earth's interior. We used high-energy lasers at the National Ignition Facility and in situ x-ray diffraction to determine the melting point of iron up to 1000 gigapascals, three times the pressure of Earth's inner core. We used this melting curve to determine the length of dynamo action during core solidification to the hexagonal close-packed (hcp) structure. We find that terrestrial exoplanets with four to six times Earth's mass have the longest dynamos, which provide important shielding against cosmic radiation.
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Objective. The goal of this project was to establish content validity and describe internal consistency of a patient counseling competency assessment instrument used to evaluate student pharmacists practicing in an oncology setting.Methods. The study involved a modified e-Delphi panel of oncology clinical pharmacy specialists, clinical pharmacy generalists, and oncology pharmacy residents. Iterative rounds of the e-Delphi process were conducted until consensus was reached on most instrument items. Consensus was defined as agreement by at least 75% of participants that an item was or was not important.Results. The modified e-Delphi process included three rounds of responses from 13 panelists and resulted in a 35-item instrument with consensus reached on 33/35 (94%) of the items. All participants indicated that the assessment result options allowed them to indicate the student's level of competency either extremely well or very well.Conclusion. A modified e-Delphi method was used to validate a reliable instrument for the assessment of student pharmacist counseling abilities in an oncology setting. Similar methodology should be considered during the development of student assessment tools, especially for high-impact student pharmacist activities such as chemotherapeutic medication counseling.
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Educação em Farmácia , Farmacêuticos , Aconselhamento , Técnica Delphi , Humanos , EstudantesRESUMO
Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination therapy yields high complete remission and disease-free survival rates in acute promyelocytic leukemia (APL). ATO is dosed on actual body weight and high ATO doses in overweight patients may contribute to increased toxicity. We performed a retrospective, two-center study comparing toxicities in patients who received the Lo-Coco et al ATRA/ATO regimen with capped ATO, ≤10 mg/dose, and non-capped ATO, >10 mg/dose. A total of 44 patients were included; 15 received doses ≤10 mg and 29 received >10 mg. During induction, there was no difference in the incidence of grade ≥3 hepatotoxicity, grade ≥3 QTc prolongation, neurotoxicity, and cardiac toxicity between groups. In consolidation, patients receiving >10 mg/dose experienced a greater incidence of neurotoxicity (66.7% vs 22.2%; p = 0.046). Capping doses saved $24634.37/patient and reduced waste of partially-used vials. At a median follow-up of 27 months, no disease relapses occurred in either group. This represents an opportunity to improve the safety profile of this highly effective regimen.
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Arsenicais , Leucemia Promielocítica Aguda , Protocolos de Quimioterapia Combinada Antineoplásica , Trióxido de Arsênio/efeitos adversos , Arsenicais/efeitos adversos , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína/efeitos adversosRESUMO
Climate variability in the tropical Pacific affects global climate on a wide range of time scales. On interannual time scales, the tropical Pacific is home to the El NiñoSouthern Oscillation (ENSO). Decadal variations and changes in the tropical Pacific, referred to here collectively as tropical Pacific decadal variability (TPDV), also profoundly affect the climate system. Here, we use TPDV to refer to any form of decadal climate variability or change that occurs in the atmosphere, the ocean, and over land within the tropical Pacific. "Decadal," which we use in a broad sense to encompass multiyear through multidecadal time scales, includes variability about the mean state on decadal time scales, externally forced mean-state changes that unfold on decadal time scales, and decadal variations in the behavior of higher-frequency modes like ENSO.
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Ivosidenib and enasidenib are targeted agents that inhibit mutant isocitrate dehydrogenase (IDH) enzymes, restoring normal cellular differentiation in affected acute myeloid leukemia patients. Both agents carry a risk of differentiation syndrome (DS), a potentially life-threatening complication. In this multicenter, retrospective study we sought to determine the real-world incidence and characterize DS in patients with a myeloid malignancy treated with an IDH inhibitor. Of 49 total patients, 15 patients (31%) had a documented diagnosis of DS and 8 patients (16%) met the criteria of DS by Montesinos, et al. The most common signs and symptoms of DS were dyspnea/hypoxia (56%), unexplained fever (56%), bone pain/arthralgia (44%), edema/weight gain (39%), and pleural/pericardial effusions (33%). Our study reports a higher real-world incidence of DS in patients treated with IDH inhibitors for myeloid malignancies than previously reported.
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Antineoplásicos , Leucemia Mieloide Aguda , Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Humanos , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/diagnóstico , Mutação , Estudos Retrospectivos , SíndromeRESUMO
OBJECTIVE: Acute myeloid leukemia (AML) is primarily a disease of older adults. These patients may not be candidates for intensive treatment, and there has been an ongoing need for treatment options for this group. We review the use of glasdegib, a hedgehog-pathway inhibitor available for use in combination with low-dose cytarabine (LDAC).Data Sources: PubMed and relevant congress abstracts were searched using the term "glasdegib". In addition, based on our experience with glasdegib, we considered treatment aspects of particular relevance to pharmacists and advanced practitioners.Data Summary: In a randomized phase II study, the combination of glasdegib plus LDAC demonstrated superior overall survival versus LDAC alone (hazard ratio 0.51, 80% confidence interval 0.39-0.67, p = 0.0004). The trial reported adverse events (AEs) of special relevance for older patients, such as hematologic events, gastrointestinal toxicity, and fatigue, as well as AEs associated with Hh-pathway inhibitors (alopecia, muscle spasms, dysgeusia). Educating patients about typical AEs can facilitate adherence as well as early AE identification and proactive management. For LDAC, which is a long-established therapy in AML, various stages of delivery need consideration, with attention to individual circumstances. Practical measures such as dispensing a longer supply can reduce the number of return clinic visits, providing a meaningful difference for many patients. CONCLUSIONS: Pharmacists and advanced practitioners play important roles in treatment with glasdegib plus LDAC. Ultimately, framing plans for treatment delivery within the individual circumstances of each patient may enable them to stay on therapy longer, giving them the greatest potential to achieve benefit.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzimidazóis/administração & dosagem , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Farmacêuticos/normas , Compostos de Fenilureia/administração & dosagem , Médicos/normas , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/efeitos adversos , Citarabina/efeitos adversos , Interações Medicamentosas/fisiologia , Feminino , Gastroenteropatias/induzido quimicamente , Doenças Hematológicas/induzido quimicamente , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Compostos de Fenilureia/efeitos adversosRESUMO
We report the synthesis and antimicrobial studies of a new series of naphthyl-substituted pyrazole-derived hydrazones. Many of these novel compounds are potent growth inhibitors of several strains of drug-resistant bacteria. These potent compounds have inclined growth inhibitory properties for planktonic Staphylococcus aureus and Acinetobacter baumannii, and its drug-resistant variants with minimum inhibitory concentration (MIC) as low as 0.78 and 1.56 µg ml-1, respectively. These compounds also show potent activity against S. aureus and A. baumannii biofilm formation and eradication properties. Time Kill Assay shows that these compounds are bactericidal for S. aureus and bacteriostatic for A. baumannii. The probable mode of action is the disruption of the bacterial cell membrane. Furthermore, potent compounds are nontoxic to human cell lines at several fold higher concentrations than the MICs.
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Desenho de Fármacos , Hidrazonas/síntese química , Staphylococcus aureus/efeitos dos fármacos , Acinetobacter baumannii/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana , Hidrazonas/farmacologia , Testes de Sensibilidade Microbiana , Naftalenos/síntese química , Naftalenos/farmacologiaRESUMO
COVID-19 has affected many National Health Service Scotland services. Our aim is to describe this impact on the Scottish National Spine Deformity Service (SNSDS). All referrals to the SNSDS from 1 January 2020 to 30 June 2020 were analysed and compared with the same period in 2019. There was a 64.3% decline in referrals during the pandemic to the SNSDS. The mean waiting time to be seen in first clinical appointment for a new referral was 6.5 weeks in 2020 compared with 10.9 in 2019. There were 60 patients still waiting to be seen at the end of the study period.