-
Pharmaceutics Jun 2024Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to...
Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.
Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.
PubMed: 38931936
DOI: 10.3390/pharmaceutics16060815 -
Pharmaceutics Jun 2024Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic...
OBJECTIVE
Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic headache (PTH), for which there are presently no approved treatments. A crucial gap in knowledge exists regarding the consequences of an mTBI, which could serve as a foundation for the development of therapeutic approaches. The activation of trigeminal sensory nerve terminals that innervate the calvarial periosteum (CP)-a densely innervated tissue layer covering the calvarial skull-has been implicated in both migraines and PTHs. We have previously shown that trigeminal oxytocin receptors (OTRs) may provide a therapeutic target for PTHs. This study examined the expression of oxytocin receptors on trigeminal nerves innervating the periosteum and whether these receptors might serve as a therapeutic target for PTHs using a direct application of oxytocin to the periosteum in a rodent model of PTH.
METHODS
We used retrograde tracing and immunohistochemistry to determine if trigeminal ganglion (TG) neurons innervating the periosteum expressed OTRs and/or CGRPs. To model the impact of local inflammation that occurs following an mTBI, we applied chemical inflammatory mediators directly to the CP and assessed for changes in immediate-early gene expression as an indication of neuronal activation. We also determined whether mTBI would lead to expression changes to OTR levels. To determine whether these OTRs could be a viable therapeutic target, we assessed the impact of oxytocin injections into the CP in a mouse model of PTH-induced periorbital allodynia.
RESULTS
The results of these experiments demonstrate the following: (1) the cell bodies of CP afferents reside in the TG and express both OTRs and CGRPs; (2) inflammatory chemical stimulation of the periosteum leads to rapid activation of TG neurons (phospho-ERK (p-ERK) expression), (3) mTBI-induced inflammation increased OTR expression compared to the sham group; and (4) administration of oxytocin into the periosteum on day 2 and day 40 blocked cutaneous allodynia for up to one hour post-administration for both acute and persistence phases in the PTH model-an effect that was preventable by the administration of an OTR antagonist.
CONCLUSION
Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin.
PubMed: 38931882
DOI: 10.3390/pharmaceutics16060760 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved... (Review)
Review
Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank = 0.55) and BPs (rank = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.
PubMed: 38931478
DOI: 10.3390/ph17060811 -
Nutrients Jun 2024In the original publication [...].
Correction: Hill et al. A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis. 2023, , 3769.
In the original publication [...].
PubMed: 38931329
DOI: 10.3390/nu16121961 -
Nutrients Jun 2024Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that improves IBS symptoms in adults. This...
Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that improves IBS symptoms in adults. This real-world, single-arm, open-label study conducted in Chile investigated the effects of 35624 (1 × 10 colony-forming units, 12 weeks) on gastrointestinal symptoms (adapted IBS severity scoring system [IBS-SSS]; adapted Questionnaire on Pediatric Gastrointestinal Symptoms [QPGS], and Bristol Stool Form Scale) in 64 children and adolescents (8-18 years) and explored the relationship with baseline vitamin D status. Improvements in all IBS-SSS domains and composite score were observed at week 6 and 12 ( < 0.0007 versus baseline), with 98.3% of participants experiencing numerical improvements in ≥3 domains. Clinically meaningful improvement was seen in 96.6% of participants. The distribution of IBS-SSS severity categories shifted from moderate/severe at baseline to mild/remission ( < 0.0001). Improvements were not maintained during the two-week washout. Low baseline serum vitamin D levels did not correlate to IBS severity or probiotic response. QPGS significantly decreased from baseline to week 6 ( = 0.0005) and 12 ( = 0.02). 35624 may improve IBS symptoms in children and adolescents, even those with vitamin D deficiency. A confirmatory randomized controlled trial and further exploration of probiotic response and vitamin D status are needed.
Topics: Humans; Irritable Bowel Syndrome; Adolescent; Child; Probiotics; Male; Female; Bifidobacterium longum; Chile; Treatment Outcome; Severity of Illness Index; Vitamin D; Vitamin D Deficiency
PubMed: 38931319
DOI: 10.3390/nu16121967 -
Nutrients Jun 2024Chronic stress (CS) endangers the physical and mental health of adolescents. Therefore, alleviating and preventing such negative health impacts are a top priority. This...
Microbiome and Metabolite Analysis Insight into the Potential of Shrimp Head Hydrolysate to Alleviate Depression-like Behaviour in Growth-Period Mice Exposed to Chronic Stress.
Chronic stress (CS) endangers the physical and mental health of adolescents. Therefore, alleviating and preventing such negative health impacts are a top priority. This study explores the effect of feeding shrimp head hydrolysate (SHH) on gut microbiota, short-chain fatty acids (SCFAs), and neurotransmitters in growing C57BL/6 mice subjected to chronic unpredictable mild stress. Mice in the model group and three SHH groups were exposed to CS for 44 days, distilled water and SHH doses of 0.18, 0.45, 0.90 g/kg·BW were given respectively by gavage daily for 30 days from the 15th day. The results showed that SHH can significantly reverse depression-like behaviour, amino acids degradation, α diversity and β diversity, proportion of Firmicutes and Bacteroidota, abundance of genera such as , , , and , concentration of five short-chain fatty acids (SCFAs), 5-HT and glutamate induced by CS. and butyric acid may be a controlled target. This study highlights the potential and broad application of SHH as an active ingredient in food to combat chronic stress damage.
Topics: Animals; Gastrointestinal Microbiome; Mice, Inbred C57BL; Stress, Psychological; Mice; Fatty Acids, Volatile; Depression; Male; Behavior, Animal; Disease Models, Animal
PubMed: 38931307
DOI: 10.3390/nu16121953 -
Nutrients Jun 2024Fatty liver disease has been identified as a marker of malnutrition in different clinical settings. Recently, the COntrolling NUTritional status score (CONUT score)...
Fatty liver disease has been identified as a marker of malnutrition in different clinical settings. Recently, the COntrolling NUTritional status score (CONUT score) emerged as a promising tool for malnutrition assessment. Our aim was to evaluate short-term outcomes among patients with malnutrition-related liver steatosis in an Internal Medicine department. Furthermore, we evaluated the association of the CONUT score with malnutrition-related liver steatosis. Data from 247 patients hospitalized in an Internal Medicine department were retrospectively collected. The study population was stratified into three groups based on hepatic radiodensity assessed with computed tomography: mild steatosis (≥56.1 HU), moderate steatosis (between 49.7 and 56 HU), and severe steatosis (≤49.6 HU). We then calculated the CONUT score. Severe steatosis patients had higher in-hospital mortality (18.2 vs. 15.5%) and longer in-hospital stays compared with the mild steatosis group (length of in-hospital stay longer than 12 days: 45% vs. 40%). Logistic regression analysis showed that severe steatosis was not significantly associated with in-hospital all-cause death, while a high CONUT score was an independent risk factor for sepsis. We found an independent relationship between malnutrition-associated liver steatosis and the CONUT score. These results identified the CONUT score as a tool for nutritional assessment of hospitalized patients.
Topics: Humans; Male; Malnutrition; Female; Internal Medicine; Aged; Retrospective Studies; Nutrition Assessment; Hospital Mortality; Nutritional Status; Middle Aged; Fatty Liver; Length of Stay; Risk Factors; Aged, 80 and over; Severity of Illness Index; Tomography, X-Ray Computed; Sepsis
PubMed: 38931279
DOI: 10.3390/nu16121925 -
Nutrients Jun 2024Premenstrual Syndrome (PMS) is a disorder between gynecology and psychiatry which includes cognitive, affective, and somatic symptoms from mild to severe. The most... (Review)
Review
Premenstrual Syndrome (PMS) is a disorder between gynecology and psychiatry which includes cognitive, affective, and somatic symptoms from mild to severe. The most severe form of PMS is premenstrual dysphoric disorder (PMDD) and it is considered a form of depressive disorder. An association between diet composition and the occurrence of PMS and its severity have been suggested. As such, this manuscript discusses the relationships between diet composition, dietary patterns and eating behaviors, and PMS. PubMed, Embase, Cochrane, and Web of Science databases were searched for related studies up to 18 January 2024. A text search with the following keywords singly or in combination was conducted: "Premenstrual syndrome", "Nutrition", "Diet composition", "Dietary patterns", and "Eating behaviors". Studies published so far showed that low intake of simple carbohydrates, fats, salt, and alcohol, and high of fresh, unprocessed foods rich in B vitamins, vitamin D, zinc, calcium, and omega-3 fatty acids may help prevent the onset of PMS and reduce the severity of its symptoms. However, further studies are needed to formulate definitive recommendations for the use of vitamins, micronutrients and other dietary ingredients supplementation in women with PMS to improve functioning, overall well-being, and physical health. Large, randomized, double-blind clinical trials across diverse populations are necessary to formulate clear recommendations for supplementation in women with PMS.
Topics: Humans; Premenstrual Syndrome; Female; Diet; Feeding Behavior; Adult; Nutritional Status; Dietary Patterns
PubMed: 38931266
DOI: 10.3390/nu16121911 -
Nutrients Jun 2024Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity... (Observational Study)
Observational Study
UNLABELLED
Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound.
OBJECTIVE
To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks.
DESIGN, PATIENTS AND SETTING
A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain).
INTERVENTIONS
Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines.
MEASUREMENTS
Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis.
RESULTS
Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol ( = 68), glucocorticoids ( = 112), both ( = 510), or neither ( = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) ( < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both ( = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol ( < 0.001). This difference was not found for corticosteroids.
INTERPRETATION
The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.
Topics: Humans; Male; Female; Retrospective Studies; COVID-19 Drug Treatment; Middle Aged; Aged; COVID-19; Adrenal Cortex Hormones; Spain; SARS-CoV-2; Intensive Care Units; Hospitalization; Prognosis; Aged, 80 and over; Glucocorticoids
PubMed: 38931265
DOI: 10.3390/nu16121910 -
Nutrients Jun 2024Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity... (Review)
Review
Morphofunctional assessment was developed to evaluate disease-related malnutrition. However, it can also be used to assess cardiometabolic risk, as excess adiposity increases this risk. Phenylketonuria (PKU) is the most prevalent inherited metabolic disease among adults, and obesity in PKU has recently gained interest, although fat mass correlates better with cardiometabolic risk than body mass index. In this systematic review, the objective was to assess whether adult patients with PKU have higher fat mass than healthy controls. Studies of adult PKU patients undergoing dietary treatment in a metabolic clinic reporting fat mass were included. The PubMed and EMBASE databases were searched. Relevance of articles, data collection, and risk of bias were evaluated by two independent reviewers. Ten articles were evaluated, six with a control group, including 310 subjects with PKU, 62 with mild hyperphenylalaninemia, and 157 controls. One study reported a significant and four a tendency towards an increased fat mass in all patients or only females with PKU. Limitations included not having a healthy control group, not reporting sex-specific results and using different techniques to assess fat mass. Evaluation of fat mass should be included in the morphofunctional assessment of cardiometabolic risk in adult patients with PKU.
Topics: Humans; Phenylketonurias; Adult; Female; Male; Malnutrition; Adiposity; Body Mass Index; Obesity; Cardiometabolic Risk Factors; Adipose Tissue
PubMed: 38931188
DOI: 10.3390/nu16121833