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OBJECTIVE: To describe ophthalmic findings in hospitalized canine and feline patients with tick paralysis (TP) and investigate possible predisposing factors. ANIMALS STUDIED: Forty-seven dogs and 28 cats hospitalized with TP assessed with an ophthalmic examination performed by an ABVO resident. METHODS: Dogs and cats were hospitalized with TP from October 2021 to January 2022 and had an ophthalmic examination performed by an ABVO resident. Patient signalment data, information regarding tick number and location, hospitalization duration, medications used, and patient paralysis grades were recorded. Statistical analysis was performed to correlate findings. RESULTS: Corneal ulcers developed in up to 34.8% of dogs and up to 42.9% of cats hospitalized with TP. An absent palpebral reflex ipsilaterally increased the odds of a concurrent corneal ulcer being present by 14.7× in dogs and 20.1× in cats (p < .0001). Palpebral reflexes were absent in 38.3% of dogs and 35.7% of cats hospitalized with TP and were correlated with more severe gait paralysis (p = .01) and respiratory paralysis (p = .005) in dogs, and respiratory paralysis in cats (p = .041). STT-1 findings <10 mm/min were present in 27.7% of dogs and 57.1% of cats examined and were associated with increasing gait paralysis (p = .017) and respiratory paralysis (p = .007) in dogs, and increasing gait paralysis in cats (p = .017). CONCLUSIONS: Simple corneal ulcers, loss of a complete palpebral reflex, and reduced STT-1 scores frequently occurred in dogs and cats hospitalized for TP. The frequency of these findings increased as the degree of patient paralysis increased.
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OBJECTIVE: Prior research suggests that restless leg syndrome (RLS) is prevalent in Parkinson's disease (PD) with insufficient evidence to support the relationship between RLS, PD, and pain. This study explored the relationship between pain in PD patients and its association with the prevalence and severity of RLS. METHOD: 127 PD patients were assessed for PD and RLS using the U.K. Brain bank Criteria and the Restless Leg Syndrome diagnostic criteria, respectively. These patients were also assessed for pain perception and interference using the Brief Pain Inventory. RESULTS: The results demonstrated Parkinson's disease patients who reported pain scored 23 more Restless Leg Syndrome prevalence points (p < 0.05), and 8.5 counts higher for Restless Leg Syndrome severity (p < 0.05) compared to the group of Parkinson's disease patients denying pain. DISCUSSION: The presence of pain in PD patients indicated a higher RLS prevalence and an increased RLS severity. This finding suggests patients suffering from pain interference may experience more severe RLS symptoms. This demonstrates an inextricable link and association between pain in PD patients and RLS. Further robust investigations are required to elucidate any potential causative links, which can inform more holistic treatment principles.
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Doença de Parkinson , Síndrome das Pernas Inquietas , Estudos Transversais , Humanos , Dor/complicações , Dor/epidemiologia , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Doença de Parkinson/epidemiologia , Prevalência , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/epidemiologiaRESUMO
An Ocular Sebaceous Carcinoma (OSC) is a rare malignant tumor for which initial clinical and pathological diagnosis is often incorrect. OSCs can mimic Squamous Cell Carcinomas of the Conjunctiva (SCCC). The aim of this study was to find microRNA biomarkers to distinguish OSCs and SCCCs from normal tissue and from each other. Clinical OSC and SCCC case files and the corresponding histopathological slides were collected and reviewed. Micro dissected formalin-fixed paraffin-embedded tumor and control tissues were subjected to semi-high throughput microRNA profiling. MicroRNA expression distinguishes OSCs and SCCCs from corresponding control tissues. Selected differentially expressed miRNAs were validated using single RT-PCR assays. No prognostic miRNAs could be identified that reliably predict SCCC metastasis or OSC recurrence. A comparison between OSCs (n = 14) and SCCCs (n = 18) revealed 38 differentially expressed microRNAs (p < 0.05). Differentially expressed miRNAs were selected for validation in the discovery cohort and an independent validation cohort (OSCs, n = 11; SCCCs, n = 12). At least two miRNAs, miR-196b-5p (p ≤ 0.05) and miR-107 (p ≤ 0.001), displayed a statistically significant differential expression between OSCs and SCCCs with miR-196b-5p upregulated in SCCCs and miR-107 upregulated in OSCs. In the validation cohort, microRNA miR-493-3p also showed significant upregulation in SCCCs when compared to OSCs (p ≤ 0.05). ROC analyses indicated that the combined miR-196b-5p and miR-107 expression levels predicted OSCs with 90.0% sensitivity and 83.3% specificity. In conclusion, the combined testing of miR-196b-5p and miR-107, can be of additional use in routine diagnostics to discriminate OSCs from SCCCs.
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Carcinoma de Células Escamosas , Neoplasias Oculares , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , MicroRNAs , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Neoplasias Oculares/genética , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
Studying spin-momentum correlations in hadronic collisions offers a glimpse into a three-dimensional picture of proton structure. The transverse single-spin asymmetry for midrapidity isolated direct photons in p^{↑}+p collisions at sqrt[s]=200 GeV is measured with the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). Because direct photons in particular are produced from the hard scattering and do not interact via the strong force, this measurement is a clean probe of initial-state spin-momentum correlations inside the proton and is in particular sensitive to gluon interference effects within the proton. This is the first time direct photons have been used as a probe of spin-momentum correlations at RHIC. The uncertainties on the results are a 50-fold improvement with respect to those of the one prior measurement for the same observable, from the Fermilab E704 experiment. These results constrain gluon spin-momentum correlations in transversely polarized protons.
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Among the various non-motor symptoms of Parkinson's disease (PD), pain is often cited as the most common and debilitating feature. Currently, the literature contains gaps in knowledge with respect to the various forms of treatment available, particularly non-pharmacological therapies. Thus, the purpose of this systematic review is to provide an examination of the literature on non-pharmacological therapies for pain in PD. We compared the findings of research articles indexed within various literature databases related to non-pharmacological treatments of pain in PD patients. Our review identified five major non-pharmacological methods of pain therapy in PD: acupuncture, hydrotherapy, massage therapy, neuromodulation, and exercise. Treatments such as exercise therapy found a reduction in pain perception due to various factors, including the analgesic effects of neurotransmitter release during exercise and increased activity leading to a decrease in musculoskeletal rigidity and stiffness. By the same token, hydrotherapy has been shown to reduce pain perception within PD patients, with authors often citing a combined treatment of exercise and hydrotherapy as an effective treatment for pain management. Multiple methods of neurostimulation were also observed, including deep brain stimulation and spinal cord stimulation. Deep brain stimulation showed efficacy in alleviating certain pain types (dystonic and central), while not others (musculoskeletal). Hence, patients may consider deep brain stimulation as an additive procedure for their current treatment protocol. On the other hand, spinal cord stimulation showed significant improvement in reducing VAS scores for pain. Finally, although the literature on massage therapy and acupuncture effectiveness on pain management is limited, both have demonstrated a reduction in pain perception, with common reasons such as tactile stimulation and release of anti-nociceptive molecules in the body. Although literature pertaining to non-pharmacological treatments of pain in PD is sparse, there is copious support for these treatments as beneficial to pain management. Further exploration in the form of clinical trials is warranted to assess the efficacy of such therapies.
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Manejo da Dor/métodos , Dor/etiologia , Doença de Parkinson/complicações , Analgesia por Acupuntura/métodos , Terapia por Exercício/métodos , Humanos , Hidroterapia/métodos , Massagem/métodos , Estimulação Elétrica Nervosa Transcutânea/métodosRESUMO
PURPOSE: To understand the association between heart rate variability and indices of fatigue, total sleep time, and reaction time in shift workers. METHODS: Ten participants from the British Columbia Wildfire Service management team were examined over a 14-day active fire-line period. Daily measures of subjective fatigue, sleepiness, and alertness were recorded using a visual analog scale. Daily total sleep time was recorded using a wrist actigraph. Cardiac autonomic modulation was examined each morning using heart rate variability (HRV). Three measures of reaction time (simple reaction time, choice reaction tie, and discriminatory reaction time) was examined on days 1, 5, 10, and 14. Multiple linear regression analysis was utilized to examine the association between HRV and indices of fatigue, total sleep time, and reaction time. RESULTS: Mean shift duration was 13.8 ± 0.77 h. Significant inverse associations were observed between HRV and sleepiness [r = - 0.60, p = 0.000] and fatigue [r = - 0.55, p = 0.000], and a positive association with total sleep time (min) [r = 0.28, p = 0.009]. There were no significant relationships between HRV and simple reaction time (ms) [r = - 0.32, p = 0.182], choice reaction time (ms) [r = - 0.10, p = 0.850], or discriminatory reaction time (ms) [r = - 0.09, p = 0.881]. CONCLUSIONS: HRV displayed significant associations with indices of fatigue and sleep, whereby demonstrating its utility as a practical tool for monitoring the development of fatigue in wildland firefighters and for providing insight when to make lifestyle modifications to preserve alertness.
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Fadiga/fisiopatologia , Bombeiros , Frequência Cardíaca , Jornada de Trabalho em Turnos , Sono/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação , Local de TrabalhoRESUMO
Peripheral neuropathy (PN) is a common neurological problem defined as a dysfunction of sensory, motor, and autonomic nerves. The presence of peripheral neuropathy has recently been noticed in Parkinson's disease (PD) This comorbidity is concerning as it increases the burden on patients whose motor functions are previously compromised. A comprehensive computer-based literature review utilizing multiple peer-reviewed databases (e.g., Embase, PsycINFO, CINAHL, etc.) was conducted. There is evidence for the utility of robust diagnostic criteria to distinguish between large fiber neuropathy (LFN) and small fiber neuropathy (SFN). Some studies have established links between prolonged L-DOPA exposure and prevalence with increased levels of homocysteine (HCY) and methylmalonic acid (MMA) as pathological underlying mechanisms. PN in PD patients with relatively truncated exposure to L-DOPA therapy may have underlying mutations in the Parkin and MHTFR gene or separate mitochondrial disorders. Vitamin B12 and cobalamin deficiencies have also been implicated as drivers of PN. Accumulation of phosphorylated α-synuclein is another central feature in PN and deems urgent exploration via large cohort studies. Importantly, these underlying mechanisms have been linked to peripheral denervation. This review delves into the potential treatments for PN targeting B12 deficiencies and the use of COMT inhibitors along with other novel approaches. Avenues of research with powerful randomized controlled and long-term cohort studies exploring genetic mechanisms and novel treatment pathways is urgently required to alleviate the burden of disease exerted by PN on PD.
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Doença de Parkinson , Doenças do Sistema Nervoso Periférico , Humanos , Levodopa , Ácido Metilmalônico , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Doenças do Sistema Nervoso Periférico/etiologia , Vitamina B 12RESUMO
We report on the nuclear dependence of transverse single-spin asymmetries (TSSAs) in the production of positively charged hadrons in polarized p^{↑}+p, p^{↑}+Al, and p^{↑}+Au collisions at sqrt[s_{NN}]=200 GeV. The measurements have been performed at forward rapidity (1.4<η<2.4) over the range of transverse momentum (1.8
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From a prospective and multicentric French cohort, we proposed an external validation study for the expanded criteria donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95% confidence interval [CI] 1.53-2.00, P < .0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (standard criteria donor [SCD]). Complementarily, we estimated the population-average effect using propensity scores. We estimated a 1.34-fold (95% CI 1.09-1.64, P = .0049) increase in graft failure risk among ECD patients receiving an ECD graft compared to receiving a SCD graft. With a 10-year follow-up, it corresponded to a decrease of 8 months of the mean time to graft failure due to ECD transplantation (95% CI 2-14 months). The population-average relative risk due to ECD transplantation and the corresponding absolute effect seem finally not so high. Regarding the increase of quality of life in transplantation, our study constitutes an argument to extend the definition of marginality by considering more grafts at high risk and thereby enlarging the pool of kidney grafts.
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Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Pontuação de Propensão , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Idoso , Seleção do Doador , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Obtenção de Tecidos e Órgãos/normas , TransplantadosRESUMO
Recently, multiparticle-correlation measurements of relativistic p/d/^{3}He+Au, p+Pb, and even p+p collisions show surprising collective signatures. Here, we present beam-energy-scan measurements of two-, four-, and six-particle angular correlations in d+Au collisions at sqrt[s_{NN}]=200, 62.4, 39, and 19.6 GeV. We also present measurements of two- and four-particle angular correlations in p+Au collisions at sqrt[s_{NN}]=200 GeV. We find the four-particle cumulant to be real valued for d+Au collisions at all four energies. We also find that the four-particle cumulant in p+Au has the opposite sign as that in d+Au. Further, we find that the six-particle cumulant agrees with the four-particle cumulant in d+Au collisions at 200 GeV, indicating that nonflow effects are subdominant. These observations provide strong evidence that the correlations originate from the initial geometric configuration, which is then translated into the momentum distribution for all particles, commonly referred to as collectivity.
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During 2015, the Relativistic Heavy Ion Collider (RHIC) provided collisions of transversely polarized protons with Au and Al nuclei for the first time, enabling the exploration of transverse-single-spin asymmetries with heavy nuclei. Large single-spin asymmetries in very forward neutron production have been previously observed in transversely polarized p+p collisions at RHIC, and the existing theoretical framework that was successful in describing the single-spin asymmetry in p+p collisions predicts only a moderate atomic-mass-number (A) dependence. In contrast, the asymmetries observed at RHIC in p+A collisions showed a surprisingly strong A dependence in inclusive forward neutron production. The observed asymmetry in p+Al collisions is much smaller, while the asymmetry in p+Au collisions is a factor of 3 larger in absolute value and of opposite sign. The interplay of different neutron production mechanisms is discussed as a possible explanation of the observed A dependence.
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BACKGROUND: Sensitive skin syndrome (SSS) is defined as the occurrence of unpleasant sensations (itch, pain, burning, prickling) in response to stimuli that should not normally cause such sensations. Previous studies show that SSS could be a small fibre neuropathy, but quantitative sensory testing (QST) is lacking. OBJECTIVES: Using QST, to determine the presence or absence of tactile sensitivity disorder, mainly heat pain threshold (HPT), in patients with SSS. METHODS: This monocentric case-control study included 21 patients with SSS and 21 controls. The patients underwent QST. Neuropathic pain was assessed by two questionnaires: the Douleur Neuropathique 4 (DN4) and the Neuropathic Pain Symptom Inventory (NPSI). RESULTS: Forty-two patients were included in the study. The HPT was significantly lower in the cases (14·5 ± 2·8) than in the controls (17·8 ± 2·5) (P < 0·001). Intermediate pain (HPT 5·0) was also significantly decreased in patients with SSS. The DN4 and NPSI scores were significantly higher in the cases than in the controls. CONCLUSIONS: The decrease in HPT in patients with SSS compared with controls suggests the presence of hyperalgesia, probably due to the damage of C-fibres. These findings, as well as the increased DN4 and NPSI scores, strengthen the neuronal hypothesis of SSS and are new arguments for consideration of SSS as small fibre neuropathy.
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Hiperalgesia/diagnóstico , Neuralgia/diagnóstico , Pele/inervação , Neuropatia de Pequenas Fibras/diagnóstico , Adulto , Estudos de Casos e Controles , Temperatura Baixa/efeitos adversos , Feminino , Humanos , Hiperalgesia/etiologia , Pessoa de Meia-Idade , Neuralgia/etiologia , Medição da Dor , Limiar da Dor , Neuropatia de Pequenas Fibras/etiologia , Inquéritos e Questionários/estatística & dados numéricos , Síndrome , Vibração/efeitos adversos , Adulto JovemRESUMO
BACKGROUND/AIM: Anterior cruciate ligament (ACL) injury is a common and devastating sporting injury. With or without ACL reconstruction, the risk of knee osteoarthritis (OA) and permanent disability later in life is markedly increased. While neuromuscular training programmes can prevent 50-80% of ACL injuries, no national implementation strategies exist in Australia. The aim of this study was to compare the ability of four alternative national universal ACL injury prevention programme implementation strategies to reduce future medical costs secondary to ACL injury. METHODS: A Markov economic decision model was constructed to estimate the value in lifetime future medical costs prevented by implementing a national ACL prevention programme among four hypothetical cohorts: high-risk sport participants (HR) aged 12-25â years; HR 18-25â years; HR 12-17â years; all youths (ALL) 12-17â years. RESULTS: Of the four programmes examined, the HR 12-25 programme provided the greatest value, averting US$693 of direct healthcare costs per person per lifetime or US$221â 870â 880 in total. Without training, 9.4% of this cohort will rupture their ACL and 16.8% will develop knee OA. Training prevents 3764 lifetime ACL ruptures per 100â 000 individuals, a 40% reduction in ACL injuries. 842 lifetime cases of OA per 100â 000 individuals and 584 TKRs per 100â 000 are subsequently averted. Numbers needed to treat ranged from 27 for the HR 12-25 to 190 for the ALL 12-17. CONCLUSIONS: The HR 12-25 programme was the most effective implementation strategy. Estimation of the break-even cost of health expenditure savings will enable optimal future programme design, implementation and expenditure.
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Lesões do Ligamento Cruzado Anterior/economia , Lesões do Ligamento Cruzado Anterior/prevenção & controle , Modelos Econômicos , Adolescente , Adulto , Atletas , Austrália , Custos de Cuidados de Saúde , Gastos em Saúde , Humanos , Cadeias de Markov , Smartphone , Adulto JovemRESUMO
PURPOSE: Propofol is a short-acting medication with fast cognitive and psychomotor recovery. However, patients are usually instructed not to drive a motor vehicle for 24 hours after receiving propofol. The purpose of this article was to review the evidence examining when it is safe to drive after receiving propofol for sedation for diagnostic and surgical procedures. DESIGN: This is a systematic review of the literature. METHODS: A search of the literature was conducted using Google Scholar, PubMed, and the Cochrane Library for the time period 1990 to 2015. FINDINGS: Two randomized controlled trials and two observational studies met the inclusion criteria. Using a simulator, investigators examined driving ability of subjects who received modest doses (about 100 mg) of propofol for endoscopic procedures and surveyed subjects who drove immediately after discharge. There were methodological concerns with the studies such as small sample sizes, modest doses of propofol, and three of the four studies were done in Japan by the same group of investigators limiting generalizability. CONCLUSION: This limited research suggests that it may be safe for patients to drive sooner than 24 hours after receiving propofol. However, large multicenter trials using heterogenous samples using a range of propofol doses are needed to support an evidence-based revision to the current discharge guidelines for patients receiving propofol.
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Condução de Veículo , Hipnóticos e Sedativos/administração & dosagem , Propofol/administração & dosagem , Humanos , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
An early-adolescent girl presented with incoordination, headache, vomiting and dysphonia. MRI brain demonstrated diffuse increased T2 and FLAIR signal in bilateral thalami, consistent with anaplastic astrocytomas. A stereotactic burr-hole biopsy provided frozen tissues sections demonstrating an IDH-1 wildtype astrocytoma (anaplastic grade III according to prior WHO classification 2016-21). Chemoradiotherapy was commenced. Bilateral thalamic high-grade astrocytomas are very rare in the paediatric population and require timely diagnosis and interdisciplinary management. CT and MR imaging help point towards this diagnosis in the correct clinical context.
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Astrocitoma , Neoplasias Encefálicas , Criança , Feminino , Humanos , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Astrocitoma/diagnóstico por imagem , Astrocitoma/terapia , Imageamento por Ressonância Magnética/métodos , Tálamo/patologia , BiópsiaRESUMO
OBJECTIVE: To investigate the incidence and predisposing factors leading to the development of corneal ulcers and the loss of a palpebral reflex in hospitalised canine and feline patients with tick paralysis (TP). ANIMALS STUDIED: A total of 102 dogs and 100 cats retrospectively were assessed from previously hospitalised patients. METHODS: A retrospective cohort study was performed on 102 different canine and 100 different feline patients who were hospitalised for TP from October 2020-January 2022. Patient data were collected, and logistic regression was conducted to determine factors affecting the palpebral reflex and the development of corneal ulcers. RESULTS: Corneal ulcers occurred in 23/102 (22.5%) dogs during hospitalisation and were strongly associated with an incomplete palpebral reflex ipsilaterally during hospitalisation (P < 0.001), hospitalisation ≥3 days (P = 0.004), mechanical ventilation ≥3 days (P = 0.015) or a tick location cranial to C1 (P = 0.003). An incomplete palpebral reflex during hospitalisation was observed in 29/102 (28.4%) dogs and was significantly associated with decreasing patient weight (P = 0.018), increasing days hospitalised (P = 0.001), having a tick found cranial to C1 (P = 0.004), highest recorded GP grade (P = 0.01), highest recorded RP grade (P = 0.005), use of amoxycillin-clavulanic acid during hospitalisation (P = 0.002) and use of piperacillin/tazobactam during hospitalisation (P = 0.003). There was a significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in dogs (OR = 4.5, P = 0.029). Corneal ulcers occurred in 10/100 (10.0%) cats during hospitalisation, and was significantly more likely to occur to an eye if an incomplete palpebral reflex was observed ipsilaterally during hospitalisation (OR = 20.1, P < 0.0001) and with increasing patient age (P = 0.019). The absence of a complete palpebral reflex during hospitalisation was observed in 18/10 (18.0%) cats and was significantly associated with increasing days hospitalised (P = 0.034). There was no significant association between the loss of a complete palpebral reflex and mortality during hospitalisation in cats. CONCLUSIONS: The frequency of corneal ulcers and loss of palpebral reflexes were significant in dogs and cats hospitalised by TP, with many factors contributing to the risk of these developing.
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Doenças do Gato , Úlcera da Córnea , Doenças do Cão , Ixodes , Paralisia por Carrapato , Animais , Cães , Gatos , Doenças do Cão/tratamento farmacológico , Estudos Retrospectivos , Doenças do Gato/tratamento farmacológico , Paralisia por Carrapato/veterinária , Feminino , Masculino , Úlcera da Córnea/veterinária , Hospitalização/estatística & dados numéricos , Estudos de Coortes , Incidência , Fatores de RiscoRESUMO
Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.
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Adenoma , Neoplasias Colorretais , Animais , Humanos , Camundongos , Adenoma/diagnóstico , Adenoma/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Escherichia coli/genética , Estudos Prospectivos , Salicilatos , Método Duplo-CegoRESUMO
Splenunculus, or congenital accessory spleen, is a benign anatomical variation, and is rarely of clinical consideration in routine clinical practice. We describe a patient who presented with synchronous herpes simplex 1 viraemia and myelosuppression, with a splenunculus mimicking splenomegaly, and we discuss the implications on clinical practice, investigations, and management.
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Objective: To compare the outcomes of patients with refractory out-of-hospital cardiac arrest (OHCA) transported to a hospital that provides extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) with patients transported to hospitals without ECPR capability. Design, setting: Retrospective review of patient care records in a pre-hospital and hospital setting. Participants: Adult patients with OHCA who left the scene and arrived with cardiopulmonary resuscitation in progress at 16 hospitals in Melbourne, Australia, between January 2016 and December 2019. Intervention: For selected patients transported to the ECPR centre, initiation of ECMO. Main outcome measures: Survival to hospital discharge and 12-month quality of life. Results: There were 223 eligible patients during the study period. Of 49 patients transported to the ECPR centre, 23 were commenced on ECMO. Of these, survival to hospital with good neurological recovery (Cerebral Performance Category [CPC] score 1/2) occurred in 4/23 patients. Four other patients developed return of spontaneous circulation in the ECPR centre before cannulation of whom one survived, giving overall good functional outcome at 12 months survival of 5/49 (10.2%). There were 174 patients transported to the 15 non-ECPR centres and 3/174 (2%) had good functional outcome at 12 months. After adjustment for baseline differences, the odds ratio for good neurological outcome after transport to an ECPR centre compared with a non-ECPR centre was 4.63 (95% CI, 0.97-22.11; P = 0.055). Conclusion: The survival rate of patients with refractory OHCA transported to an ECPR centre remains low. Outcomes in larger cities might be improved with shorter scene times and additional ECPR centres that would provide for earlier initiation of ECMO.
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OBJECTIVES: This study sought to define the feasibility and utility of postmortem cardiac implantable electronic device (CIED) interrogation. BACKGROUND: The diagnostic yield of routine postmortem interrogation of CIEDs including pacemakers, defibrillators, and implantable loop recorders has not been established. METHODS: The study reviewed all CIED interrogations in deceased individuals undergoing medicolegal investigation of sudden or unexplained death by the Victorian Institute of Forensic Medicine between 2005 and 2020. RESULTS: A total of 260 patients (68.8% male, median age 72.8 years [interquartile range: 62.7-82.2 years]) underwent CIED interrogation (202 pacemakers, 56 defibrillators, and 2 loop recorders) for investigation of sudden (n = 162) or unexplained (n = 98) death. CIEDs were implanted for median of 2.0 years (interquartile range: 0.7-5.0 years), with 19 devices at elective replacement indicator and 5 at end of life. Interrogation was successful in 256 (98.5%) cases. Potential CIED malfunction was identified in 20 (7.7%) cases, including untreated ventricular arrhythmias (n = 13) and lead failures (n = 3, 2 resulting in untreated ventricular arrhythmia). Interrogation directly informed cause of death in 131 (50.4%) cases. A total of 72 (27.7%) patients had abnormalities recorded in 30 days preceding death: nonsustained ventricular tachycardia (n = 26), rapid atrial fibrillation (n = 17), elective replacement indicator or end-of-life status (n = 22), intrathoracic impedance alarms (n = 3), lead issues (n = 3), or therapy delivered (n = 1). In 6 cases in which the patient was found deceased after a prolonged period, interrogation determined time of death. In 1 case, CIED interrogation was the primary means of patient identification. CONCLUSIONS: Postmortem CIED interrogation frequently contributes important information regarding critical device malfunction, premortem abnormalities, mechanism, and time of death or patient identity. Device interrogation should be considered for select patients with CIEDs undergoing autopsy.