One Size Does Not Fit All: Medication Reconciliation and Review at the Hospital at Home.

Mistakes in the medication process are frequent and a common cause of morbidity and mortality. Medication reconciliation (MRec) and medication review (MRev) are the processes of creating the most accurate medication list and adapting it to optimize the effectiveness of medicines and minimize adverse effects. This is crucial in all stages of medical care, especially at discharge. The present study aims to evaluate and describe the process of MRec and MRev, with a focus on deprescribing, that we conduct at the Hospital at Home. We performed a retrospective cohort study including adult patients admitted at our Hospital at Home from 1 November 2022 to 30 April 2023. MRec and MRev were applied during hospitalization, according to patients' characteristics and clinical evolution, and then communicated to patients upon discharge. Our study involved 125 patients, with an average age of 67.6±18.0 years, and half of them had polypharmacy. We discovered discrepancies in 43.2% of patient's medication and did deprescribing in one-third of them. In the deprescribing group, patients were significantly older (mean age, 76.1 versus 66.4 years; p=0.044). It is imperative to create mechanisms to identify patients at a greater risk of adverse drug events and to minimize the burden of care and harms associated with treatments. The Hospital at Home could be an opportunity, although further research is essential.

Fat Embolism: A Rare Complication of Bone Biopsy.

We report a woman who was admitted to the hospital with a sudden onset of extensive maculopapular erythematous rash involving the trunk and extremities, six weeks after initiating antihypertensive medication. She had atypical lymphocytosis with Gumprecht shadows, elevated liver enzymes, and acute kidney injury. The diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antihypertensive drugs was suspected and the antihypertensive drugs were suspended. A hypothesis of lymphoproliferative disease was also considered, and consequently, a myelogram and bone biopsy of the iliac crest were performed. After the procedure, the patient developed acute hypoxemia. After the exclusion of pulmonary thromboembolism by CT angiography, we assumed a presumptive diagnosis of iatrogenic fat embolism syndrome (FES) associated with bone biopsy. The patient deteriorated with worsening hypoxemia and ultimately died. This case represented a diagnostic challenge and highlighted iatrogenesis's undesirable and potentially fatal effects. Careful consideration of the risk-benefit ratio of all medical procedures is paramount in daily medical practice and knowledge of the possible risks is necessary for their early recognition and therapeutic approach.

Gabapentin-Induced Cutaneous Leukocytoclastic Vasculitis: A Case Report.

Leukocytoclastic vasculitis (LCV) is a type of small vessel vasculitis, characterized by a perivascular neutrophilic inflammatory infiltrate with fibrinoid necrosis and fragmentation of nuclei ("leukocytoclasia"). Although up to half of the cases of LCV are idiopathic, infections and drugs are the most common secondary triggers for this condition. We present the case of an 88-year-old woman who developed an erythematous maculopapular rash on both thighs three days after starting gabapentin for neuropathic leg pain, without other associated symptoms. Skin biopsy was compatible with cutaneous vasculitis with a leukocytoclastic pattern. The skin lesions resolved within about 10 days after discontinuing gabapentin, supporting the diagnosis. To our knowledge, there are only four published cases of LCV secondary to gabapentin. This case highlights the importance of being alert for diagnosing drug-related cutaneous manifestations, even if the drug is used in our daily practice and vasculitis is not a common side effect, since discontinuing the suspected agent is crucial to resolve skin lesions and to avoid more serious complications.

Modification of astrocytic Cx43 hemichannel activity in animal models of AD: modulation by adenosine A2A receptors.

Increasing evidence implicates astrocytic dysfunction in Alzheimer's disease (AD), a neurodegenerative disorder characterised by progressive cognitive loss. The accumulation of amyloid-ß (Aß) plaques is a histopathological hallmark of AD and associated with increased astrocyte reactivity. In APP/PS1 mice modelling established AD (9 months), we now show an altered astrocytic morphology and enhanced activity of astrocytic hemichannels, mainly composed by connexin 43 (Cx43). Hemichannel activity in hippocampal astrocytes is also increased in two models of early AD: (1) mice with intracerebroventricular (icv) administration of Aß1-42, and (2) hippocampal slices superfused with Aß1-42 peptides. In hippocampal gliosomes of APP/PS1 mice, Cx43 levels were increased, whereas mice administered icv with Aß1-42 only displayed increased Cx43 phosphorylation levels. This suggests that hemichannel activity might be differentially modulated throughout AD progression. Additionally, we tested if adenosine A2A receptor (A2AR) blockade reversed alterations of astrocytic hemichannel activity and found that the pharmacological blockade or genetic silencing (global and astrocytic) of A2AR prevented Aß-induced hemichannel dysregulation in hippocampal slices, although A2AR genetic silencing increased the activity of astroglial hemichannels in control conditions. In primary cultures of astrocytes, A2AR-related protective effect was shown to occur through a protein kinase C (PKC) pathway. Our results indicate that the dysfunction of hemichannel activity in hippocampal astrocytes is an early event in AD, which is modulated by A2AR.

Astrocytic A2A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice.

Astrocytes are wired to bidirectionally communicate with neurons namely with synapses, thus shaping synaptic plasticity, which in the hippocampus is considered to underlie learning and memory. Adenosine A2A receptors (A2A R) are a potential candidate to modulate this bidirectional communication, since A2A R regulate synaptic plasticity and memory and also control key astrocytic functions. Nonetheless, little is known about the role of astrocytic A2A R in synaptic plasticity and hippocampal-dependent memory. Here, we investigated the impact of genetic silencing astrocytic A2A R on hippocampal synaptic plasticity and memory of adult mice. The genetic A2A R silencing in astrocytes was accomplished by a bilateral injection into the CA1 hippocampal area of a viral construct (AAV5-GFAP-GFP-Cre) that inactivate A2A R expression in astrocytes of male adult mice carrying "floxed" A2A R gene, as confirmed by A2A R binding assays. Astrocytic A2A R silencing alters astrocytic morphology, typified by an increment of astrocytic arbor complexity, and led to deficits in spatial reference memory and compromised hippocampal synaptic plasticity, typified by a reduction of LTP magnitude and a shift of synaptic long-term depression (LTD) toward LTP. These data indicate that astrocytic A2A R control astrocytic morphology and influence hippocampal synaptic plasticity and memory of adult mice in a manner different from neuronal A2A R.

Aß1-42 peptides blunt the adenosine A2A receptor-mediated control of the interplay between P2X7 and P2Y1 receptors mediated calcium responses in astrocytes.

The contribution of astrocytes to Alzheimer's disease (AD) is still ill defined. AD involves an abnormal accumulation of amyloid-ß peptides (Aß) and increased production of danger signals such as ATP. ATP can direct or indirectly, through its metabolism into adenosine, trigger adaptive astrocytic responses resulting from intracellular Ca2+ oscillations. AD also triggers an upregulation of astrocytic adenosine A2A receptors (A2AR), which blockade prevents memory dysfunction in AD. We now investigated how Aß peptides affect ATP-mediated Ca2+ responses in astrocytes measured by fluorescence live-cell imaging and whether A2AR control astrocytic Ca2+ responses mediated by ATP receptors, mainly P2X7R and P2Y1R. In primary cultures of rat astrocytes exposed to Aß1-42, ATP-evoked Ca2+ responses had a lower amplitude but a longer duration than in control astrocytes and involved P2X7R and P2Y1R, the former potentiating the later. Moreover, Aß1-42 exposure increased protein levels of P2Y1R in astrocytes. A2AR antagonism with SCH58261 controlled in a protein kinase A-dependent manner both P2X7R- and P2Y1R-mediated Ca2+ responses in astrocytes. The interplay between these purinoceptors in astrocytes was blunted upon exposure to Aß1-42. These findings uncover the ability of A2AR to regulate the inter-twinned P2X7R- and P2Y1R-mediated Ca2+ dynamics in astrocytes, which is disrupted in conditions of early AD.

Adenosine A2A receptors blockade attenuates dexamethasone-induced alterations in cultured astrocytes.

Anxiety involves abnormal glucocorticoid signalling and altered glia-neuron communication in brain regions processing emotional responses. Adenosine A2A receptor (A2AR) blockade ameliorates mood and memory impairments by preventing synaptic dysfunction and astrogliosis. Since the glucocorticoid dexamethasone (DEX) can mimic early life-stress conditions, leading to anxiety-like behaviours, we now tested if A2AR blockade prevents alterations in the morphology and function of astrocytes exposed to DEX. Cultured astrocytes exposed to DEX exhibited an up-regulation of astrocytic markers (GFAP, connexin-43 and glutamine synthetase), as well as of A2AR. Moreover, DEX enhanced ATP and glutamate release and increased basal astrocytic Ca2+ levels. The selective A2AR antagonist SCH58261 prevented DEX-induced alterations in ATP release and basal Ca2+ levels but did not affect DEX-induced alteration of glutamate release and astrocytic markers. These findings suggest that alterations in astrocytes function, which might contribute to abnormal glucocorticoid brain signalling, are controlled by A2AR, and therefore, reinforce the relevance of A2AR as a potential therapeutic target to manage mood disorders.

Association Between Adenosine A2A Receptors and Connexin 43 Regulates Hemichannels Activity and ATP Release in Astrocytes Exposed to Amyloid-ß Peptides.

Increasing evidence implicates astrocytes and the associated purinergic modulation in Alzheimer's disease (AD), characterized by cognitive deficits involving the extracellular amyloid-ß peptides (Aß) accumulation. Aß can affect astrocytic gliotransmitters release, namely ATP, which is rapidly metabolized into adenosine by ecto-5'-nucleotidase, CD73, resulting in adenosine A2A receptors (A2AR) activation that bolsters neurodegeneration. AD's brains exhibit an upregulation of A2AR and of connexin 43 (Cx43), which in astrocytes forms hemichannels that can mediate ATP release. However, a coupling between astrocytic A2AR and Cx43 remains to be established. This was now investigated using astrocytic primary cultures exposed to Aß1-42 peptides. Aß triggered ATP release through Cx43 hemichannels, a process blocked by A2AR antagonists and mimicked by selective A2AR activation. A2AR directly regulated hemichannels activity and prevented Cx43 upregulation and phosphorylation observed in Aß1-42-exposed astrocytes. Moreover, a proximity ligand assay revealed a physical association between astrocytic A2AR and Cx43. Finally, the blockade of CD73-mediated extracellular formation of ATP-derived adenosine prevented the Aß-induced increase of Cx43 hemichannel activity and of ATP release. Overall, the data identify a feed-forward loop involving astrocytic A2AR and Cx43 hemichannels, whereby A2AR increase Cx43 hemichannel activity leading to increased ATP release, which is converted into adenosine by CD73, sustaining the increased astrocytic A2AR activity in AD-like conditions.

l-α-aminoadipate causes astrocyte pathology with negative impact on mouse hippocampal synaptic plasticity and memory.

Increasing evidence shows that astrocytes, by releasing and uptaking neuroactive molecules, regulate synaptic plasticity, considered the neurophysiological basis of memory. This study investigated the impact of l-α-aminoadipate (l-AA) on astrocytes which sense and respond to stimuli at the synaptic level and modulate hippocampal long-term potentiation (LTP) and memory. l-AA selectivity toward astrocytes was proposed in the early 70's and further tested in different systems. Although it has been used for impairing the astrocytic function, its effects appear to be variable in different brain regions. To test the effects of l-AA in the hippocampus of male C57Bl/6 mice we performed two different treatments (ex vivo and in vivo) and took advantage of other compounds that were reported to affect astrocytes. l-AA superfusion did not affect the basal synaptic transmission but decreased LTP magnitude. Likewise, trifluoroacetate and dihydrokainate decreased LTP magnitude and occluded the effect of l-AA on synaptic plasticity, confirming l-AA selectivity. l-AA superfusion altered astrocyte morphology, increasing the length and complexity of their processes. In vivo, l-AA intracerebroventricular injection not only reduced the astrocytic markers but also LTP magnitude and impaired hippocampal-dependent memory in mice. Interestingly, d-serine administration recovered hippocampal LTP reduction triggered by l-AA (2 h exposure in hippocampal slices), whereas in mice injected with l-AA, the superfusion of d-serine did not fully rescue LTP magnitude. Overall, these data show that both l-AA treatments affect astrocytes differently, astrocytic activation or loss, with similar negative outcomes on hippocampal LTP, implying that opposite astrocytic adaptive alterations are equally detrimental for synaptic plasticity.

Purinergic signaling orchestrating neuron-glia communication.

This review discusses the evidence supporting a role for ATP signaling (operated by P2X and P2Y receptors) and adenosine signaling (mainly operated by A1 and A2A receptors) in the crosstalk between neurons, astrocytes, microglia and oligodendrocytes. An initial emphasis will be given to the cooperation between adenosine receptors to sharpen information salience encoding across synapses. The interplay between ATP and adenosine signaling in the communication between astrocytes and neurons will then be presented in context of the integrative properties of the astrocytic syncytium, allowing to implement heterosynaptic depression processes in neuronal networks. The process of microglia 'activation' and its control by astrocytes and neurons will then be analyzed under the perspective of an interplay between different P2 receptors and adenosine A2A receptors. In spite of these indications of a prominent role of purinergic signaling in the bidirectional communication between neurons and glia, its therapeutical exploitation still awaits obtaining an integrated view of the spatio-temporal action of ATP signaling and adenosine signaling, clearly distinguishing the involvement of both purinergic signaling systems in the regulation of physiological processes and in the control of pathogenic-like responses upon brain dysfunction or damage.

Aspectos ultrassonográficos das roturas retinianas / Retinal tears: ultrassonographic aspects

Mostrar a importância do ultrassom ocular no diagnóstico das roturas retinianas, e as diferentes formas sob as quais as roturas aparecem ao exame. Local: Trabalho realizado no Hospital CEMA. São Paulo. Método: Neste estudo foram avaliados 16 olhos com diagnóstico de rotura retiniana, comprovados prévia ou posteriormente ao exame de ultrassom. Resultados: Dos 16 olhos examinados, seis tinham hemorragia vítrea associada a descolamento do vítreo posterior, nove olhos apenas descolamento do vítreo posterior, e um olho tinha descolamento do vítreo posterior e turvação vítrea após um episódio recente de uveíte. Conclusão: O exame de ultrassonografia ocular mostrou ser útil na detecção das roturas retinianas, podendo ser utilizado como um método diagnóstico complementar, principalmente nos casos que apresentam diminuição da transparência dos meios.