A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms "pharmacokinetics", "ibuprofen", "diclofenac", "acemetacin", "naproxen", "etodolac" and "etoricoxib" was performed. From 828 articles identified, only eight met the inclusion criteria. Selective COX-2 inhibitors are associated with higher cardiovascular risk, while non-selective COX inhibitors are associated with higher gastrointestinal risk. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions. Patients with frequent NSAID use needs, such as elderly patients and patients with cardiovascular disease or impaired renal function, will benefit from lower renal excretion (e.g. acemethacin, diclofenac, and etodolac) (level of evidence 3). Polymedicated patients, elderly patients, and patients with chronic alcohol abuse will be at a lower risk for adverse effects with NSAIDs that undergo phase 2 liver biotransformation, namely, acemethacin and diclofenac (level of evidence 3). Young patients, patients dealing with acute pain, or with active and/or chronic symptomatic gastritis, selective COX-2 inhibitors (celecoxib or etoricoxib) may be a better option (level of evidence 2). Knowing the individual characteristics of the patients, combined with knowledge on basic pharmacology, offers greater safety and better adherence to therapy. PERSPECTIVE: Although there are several NSAIDs options to treat pain, physicians usually take special care to its prescription regarding cardiovascular and gastrointestinal side effects, despite the age of the patient. In this paper, based on the best evidence, the authors present a review of the safest NSAIDs to use in the elderly.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the voltage-gated potassium channels or nucleotide-gated channels that participate in calcium and magnesium homeostasis. TRP channels allowing calcium to penetrate into nerve terminals can activate apoptosis, leading to nerve terminal destruction. Further, some TRPs are activated by acid and reactive oxygen species (ROS). ROS are mainly produced in the mitochondrial respiratory chain, and an increase in ROS production and/or a decrease in the antioxidant network may induce oxidative stress (OS). Depending on the OS levels, they can promote cellular proliferation and/or cell degeneration or death. Previous studies have indicated that proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play an important role in the peripheral mediation of neuropathic pain. This article aims to perform a review of the involvement of apoptosis in pain, particularly the role of OS and neuroinflammation, and the clinical relevance of this knowledge. The potential discovery of new biomarkers and therapeutic targets can result in the development of more effective and targeted drugs to treat chronic pain, namely neuropathic pain. Highlights: Oxidative stress and neuroinflammation can activate cell signaling pathways that can lead to nerve terminal destruction by apoptosis. These could constitute potential new pain biomarkers and targets for therapy in neuropathic pain.

Frailty has been studied as a valuable predictor of adverse health events and poor postoperative outcomes in patients undergoing surgery. Thus, the use of simple and adapted indexes to define frailty, like the modified frailty index (mFI)-11, proved useful in assessing patients undergoing vascular surgery. However, the literature about the applicability of an even more pragmatic index, the modified frailty (mFI) index mFI-5 in vascular patients is scarce, particularly in those submitted to carotid endarterectomy (CEA). This study aimed to validate and estimate the prognostic value of the mFI-5 on the postoperative period and long-term survival of this population. From January 2011 to June 2019, 184 patients from a tertiary care referral center who underwent CEA with regional anesthesia for carotid artery stenosis were selected from a previous prospectively mantained cohort database. Clinical adverse events such as stroke, myocardial infarction (MI), acute heart failure (AHF), and all-cause mortality were assessed 30-days post-procedure and in the subsequent long-term surveillance period. mFI-5 was applied to this population to evaluate the impact of frailty on mortality and morbidity. The mFI-5 was significantly associated with increased risk of long-term MI (P < 0.001), AHF (P = 0.043), major adverse cardiovascular events (P = 0.001) and mortality (P < 0.001). Concerning major adverse limb events and stroke survival, mFI-5 did not reveal statistical significance. The mFI-5 was not able to predict 30-day postoperative adverse events. The mFI-5 has demonstrated to be a potential index tool capable of easily stratifying patients and predicting outcomes in the long-term and add therapeutic value in the future. The mFI-5 provides a means of rapidly comparing the comorbidity charge between cohorts.

Background: Pericarotid adipose tissue (PCAT) characteristics and systemic inflammation may play an important role in carotid endarterectomy (CEA) outcomes. This study explores the association between PCAT Hounsfield Unit (HU) ranges, radiomic features, and systemic inflammatory markers in patients undergoing carotid endarterectomy (CEA). Methods: Twenty patients undergoing CEA were included in this cross-sectional study. PCAT was analyzed using preoperative computed tomography angiography (CTA) images, with regions of interest defined around the carotid arteries. PCAT was categorized into three HU ranges: −190 to −120, −119 to −70, and −69 to −30. Radiomics features were extracted using PyRadiomics. The primary outcome was the correlation of PCAT imaging with preoperative neutrophil-to-lymphocyte ratios (NLRs). The secondary outcome was the association of PCAT imaging with the red cell distribution width (RDW-CV). Linear regression was used to evaluate associations between PCAT characteristics and inflammatory markers. Results: Distinct HU ranges in PCAT imaging showed strong correlations with the preoperative NLR. The −190 to −120 HU range demonstrated a negative association (β = −3.809, p < 0.001), whereas the −119 to −70 HU range showed a positive correlation (β = 3.814, p < 0.001). PCAT uniformity was positively associated with RDW-CV (β = 0.494, p = 0.027). Other radiomics features, such as contrast, showed trends but did not reach statistical significance. A larger outer area of PCAT was inversely associated with the NLR (β = −0.677, p < 0.001). Conclusions: Specific PCAT HU ranges and radiomics features are significantly associated with systemic inflammatory markers in CEA patients. These findings suggest that HU-based segmentation and radiomics analysis of PCAT may offer valuable insights into the relationship between local adipose tissue characteristics and systemic inflammation.

Introduction/Objectives: Community palliative care support teams specialize in providing at-home care under referral criteria distinct from hospital teams, focusing on functional status, limited benefit from continued hospital specialty care, and increased clinical complexity. This study aimed to assess the quality of referrals and the transition of care to a specialized community palliative care team, emphasizing adherence to established referral criteria. Methods: An observational, longitudinal, retrospective cohort study evaluated clinical health records of patients who received palliative care from a community team in 2023. We evaluated prior multidisciplinary follow-up, basic social support, medication changes made during the team’s first consultation, and recurrences to hospital emergency care. The data was collected from the patients’ clinical files. Results: The patient cohort had a mean age of 80.7 years (±11.92), ranging from 31 to 103 years. Males comprised 56.3% of the participants, with a median follow-up time of 32 days. Primary diagnoses included cancer (50%), end-stage organ failure (26%), and neurodegenerative disease (24%). Among the deceased, 85.6% died at home. Patients showed marked changes in psychological support and social rights, as we observed an improvement from 6.8% to 100% ( P = .0011) and from 47.1% to 100% ( P = .01) in these supports, respectively. We also observed significant changes in pharmacotherapeutic plans, regardless of the referring team. The study observed significant difficulty in recognizing referral criteria for specialized palliative care and defining clinical complexity. Referrals were often delayed, particularly for those previously under hospital care ( P = .001). Increased prescription of pro re nata medications significantly correlated with home deaths ( P = .021). Conclusions: Most complex patients can be effectively monitored and die at home, reserving hospital deaths for exceptional cases requiring interventions not possible at home or due to significant caregiver burden. There was no difference in the biopsychosocial approach of patients previously followed by other teams, including hospital palliative care teams, which suggests very different approaches.