Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy.

BACKGROUND & AIM: Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD. METHODS: The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects. RESULTS: The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation. CONCLUSION: Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.

Nitrofurantoin as an Add-On to Conventional Prophylaxis for the Treatment of Urinary Tract Infections in Kidney Recipients: A Prospective Cohort Study.

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

An overview of the current and emerging treatment options for vestibular migraine.

INTRODUCTION: Vestibular migraine is a relatively common syndrome characterized by the occurrence of vertigo and other vestibular symptoms, frequently -but not always- accompanied by migraine symptoms, such as headache, photophobia, and phonophobia. AREAS COVERED: The authors review the acute or abortive treatment during an attack and prophylactic treatment of vestibular migraines, including pharmacological and non-pharmacological options. EXPERT OPINION: Since its recognition as an independent clinical entity is recent, studies concerning its different treatment alternatives are still scarce, and the level of evidence of published studies is generally low. For acute treatment, although available data are conflicting, triptans are usually tried first. Neurostimulating devices can also be considered for acute treatment of vestibular migraine. Regarding the preventive treatment of vestibular migraine, based on the results of two randomized clinical trials and its pharmacological properties, flunarizine should be considered as the first treatment option. Second-line preventive treatments encompass propranolol, topiramate, venlafaxine, and valproic acid. Among non-pharmacological options, vestibular rehabilitation seems to be a sound prophylactic treatment option.

Caries-Prone Primary Teeth: A Hidden Reason and Prophylactic Treatment in the Viewpoint of Materials Science.

Dental caries, the most prevalent chronic disease across all age groups, has a high prevalence, particularly among children. However, there is no specific and effective treatment for the prevention of caries in primary teeth (Pr.T.), which stems from a lack of knowledge regarding the basic nature of the tooth surface. Herein, we observed that the adhesion energies of the caries-related bacteria Streptococcus mutans and Streptococcus sanguinis to Pr.T were approximately 10 and 5.5 times higher than those to permanent teeth (Pe.T). A lower degree of mineralization and more hydrophilic characteristics of the Pr.T enamel account for this discrepancy. Accordingly, we proposed that the on-target modification of both hydroxyapatite and organic components on Pr.T by dual modification would render a sufficient hydration layer. This resulted in an approximately 11-time decrease in bacterial adhesion energy after treatment. In contrast, a single hydroxyapatite modification on Pe.T and young permanent teeth (Y.Pe.T) was sufficient to achieve a similar effect. Theoretical simulation further verified the rationality of the approach. Our findings may help understand the reason for Pr.T being caries-prone and provide references for treatment using resin restorations. This strategy offers valuable insights into daily oral hygiene and dental prophylactic treatment in children.

Transient hemiplegia in a patient with migraine: A case of sporadic hemiplegic migraine.

Hemiplegic migraine is a rare form of migraine characterized by aura with unilateral paralysis; however, studies on its treatment are limited. A 39-year-old man with migraine headaches and myofascial pain syndrome was referred to our hospital with transient right hemiplegia, after presenting to an outside emergency department with headache and right hemiplegia 2 days prior. Computed tomography, magnetic resonance imaging, and blood test results revealed no abnormalities. The symptoms resolved spontaneously; he was referred to our hospital. Based on the International Classification of Headache Disorders, Third Edition criteria, he was diagnosed with sporadic hemiplegic migraine. Propranolol was added to his regular regimen as prophylactic treatment, which resulted in reduction in his migraine frequency. Over the next 2 years, no recurrent paralysis occurred. Hemiplegic migraines should be considered in patients with migraine exhibiting transient hemiplegia without obvious intracranial abnormalities. Prophylactic treatment with propranolol could be effective in treatment of hemiplegic migraine.

AGA Clinical Practice Update on Diagnosis and Management of Cyclic Vomiting Syndrome: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to review the available evidence and provide expert advice regarding the diagnosis and management of cyclic vomiting syndrome. METHODS: This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. This expert commentary incorporates important as well as recently published studies in this field, and it reflects the experiences of the authors who are experts in treating patients with cyclic vomiting syndrome.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Improving Hemophilia Care in Low- and Middle-Income Countries: Addressing Challenges and Enhancing Quality of Life.

Hemophilia, a genetic bleeding disorder caused by a deficiency in clotting factors, impacts millions of people worldwide. The quality of life (QoL) for those affected remains particularly suboptimal in low- and middle-income countries (LMICs). This article delves into the unmet needs in hemophilia care and management in LMICs, spotlighting various challenges and potential strategies for improvement. One of the primary challenges in LMICs is the limited access to comprehensive care which includes a multidisciplinary approach involving hematologists, physiotherapists, psychologists, and social workers. In many LMICs, the healthcare infrastructure is insufficient to provide such integrated services, leading to fragmented care and poorer health outcomes for individuals with hemophilia. Another significant issue is the challenge of prophylactic treatment. Prophylaxis, which involves regular infusions of clotting factor concentrates to prevent bleeding episodes, is the standard of care in high-income countries. However, in LMICs, prophylactic treatment is often not feasible due to the high cost and limited availability of clotting factor concentrates. This results in a reliance on on-demand treatment, which only addresses bleeding episodes as they occur and does not prevent the long-term complications associated with frequent bleeds. Pain management is another critical area with significant gaps. Chronic pain is a common issue for individuals with hemophilia due to repeated joint bleeds leading to joint damage. In many LMICs, access to effective pain management strategies, including both pharmacological and non-pharmacological treatments, is limited. Mental health support is also a crucial yet often overlooked aspect of hemophilia care. The chronic nature of the condition, combined with frequent hospital visits and the physical limitations imposed by the disease, can lead to mental health issues such as anxiety and depression. However, mental health services are frequently under-resourced in LMICs, and there is a lack of awareness about the mental health needs of individuals with hemophilia. Caregiver support playing a crucial role in managing the day-to-day needs of individuals with hemophilia, is another vital component of hemophilia care that is often insufficient in LMICs. Education and awareness about hemophilia are also lacking in many LMICs. There is often a limited understanding of the condition among the general public and even within the medical community, leading to misdiagnoses and delayed treatment. Employment and financial support are critical issues as well. The physical limitations and frequent medical needs associated with hemophilia can make it difficult for individuals to maintain stable employment, leading to financial strain. In many LMICs, social support systems are inadequate to address these challenges. Lastly, the integration of telehealth and digital health technologies presents a promising strategy to overcome some of these challenges providing remote access to specialist care, education, and support, which is particularly valuable in regions where healthcare resources are scarce. By adopting a multifaceted approach that involves collaboration between governments, healthcare systems, international organizations, and patient advocacy groups, it is possible to address these challenges and significantly improve the QoL for individuals with hemophilia in LMICs.

[Prophylaxis of migraine without aura of liver yang hyperactivity treated with acupuncture at the points selected using the "seven lines of the neck" method: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of prophylaxis on migraine without aura differentiated as liver yang hyperactivity undergoing acupuncture at the points selected using the "seven lines of the neck" method. METHODS: Fifty-eight patients with migraine without aura of liver yang hyperactivity at remission stage were randomly divided into an observation group (29 cases, 3 cases dropped out) and a control group (29 cases, 4 cases dropped out). In the observation group, acupuncture was delivered at Dazhui (GV 14), Fengfu (GV 16), bilateral Fengchi (GB 20), Gongxue (Extra), etc., selected using the "seven lines of the neck" method. In the control group, conventional acupuncture was applied to ashi point, Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5) and others on the affected side. The treatment was given once every other day or every two days, 3 interventions weekly, for consecutive 8 weeks. Before treatment, after 4 and 8 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit), the days of migraine episodes, the frequency of migraine episodes, the score of visual analogue scale (VAS) for pain intensity, and the score of migraine specific quality of life questionnaire (MSQ) were observed in the patients of the two groups. Before treatment and after 8 weeks of treatment, the score of TCM syndrome was observed. After 4 and 8 weeks of treatment and after 4 weeks of treatment completion (follow-up visit), the response rates of 50% reduction in the days and the frequency of migraine episodes were calculated in the two groups. RESULTS: After 4 and 8 weeks of treatment and during follow-up visit, the days and the frequency of migraine episodes were decreased (P<0.01) and VAS scores were declined (P<0.01) when compared with those before treatment in the two groups. The days and the frequency of migraine episodes in the observation group were lower during the follow-up visit (P<0.05) and VAS scores were lower after 8 weeks of treatment and during the follow-up visit (P<0.05) when compared with those in the control group. After 4 and 8 weeks of treatment, and during follow-up visit, the scores of "role function-preventive" and "emotional function" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05). After 8 weeks of treatment and during the follow-up visit, the scores of "role function-restrictive" of MSQ were increased in comparison with those before treatment in the observation group (P<0.05), and the scores of "role function-restrictive" "role function-preventive" and "emotional function" were higher when compared with those before treatment in the control group (P<0.05). After 8 weeks of treatment, the scores of TCM syndrome were decreased in comparison with those before treatment in the two groups (P<0.01). In the observation group, the response rate of 50% reduction in the days of migraine episodes after 8 weeks of treatment and that of the frequency of migraine episodes during the follow-up visit were higher than those of the control group (P<0.05). CONCLUSION: Acupuncture at the points selected using the "seven lines of the neck" method can reduce the days and frequency of migraine episodes and pain intensity, ameliorate the syndrome of TCM and improve the quality of life of the patients with migraine without aura of liver yang hyperactivity.

Efficacy of oral and non-oral migraine prophylactic treatment on self-reported subjective sleep quality in migraine patients with sleep problems: A review and meta-analysis.

This study aims to investigate the effects of oral and non-oral migraine prophylaxis on subjective sleep quality in migraine patients with sleep problems. A bidirectional relationship between migraine and sleep is presumed, although this relationship is not fully clarified. Possibly, prophylactic treatment of migraine aiming at a reduction of migraine attack frequency can also positively affect the quality of sleep for patients with migraine with sleep problems. PubMed, Cochrane, Embase and CINAHL databases were searched in March 2022 for studies evaluating prophylactic treatment of migraine and the impact on perceived sleep quality (Pittsburgh Sleep Quality Index or Insomnia Severity Index). A systematic review using the McMaster Tool and a random-effects meta-analysis (effect size Cohen's d) were conducted. Seven studies were identified, including 989 participants, of which 844/989 (85.3%) female, with a mean (SD) age of 41.3 (12.1) years. In 6/7 (85.7%) studies, monthly migraine days improved (p < 0.002). Five out of six (83.3%) studies presented a relevant improvement in quality of sleep (p < 0.05), and one study reported a clinically meaningful improvement in the treatment group (Insomnia Severity Index change >7, in >50% of participants). The meta-analysis showed a large effect size of 1.09 (95% confidence interval 0.57-1.62; overall p < 0.001; Cochran's Q < 0.0001) for migraine prophylaxis on improving sleep quality. In conclusion, prophylactic migraine treatment improves sleep quality in patients with migraine and sleep problems, as measured with self-reported questionnaires Pittsburgh Sleep Quality Index and Insomnia Severity Index. Unfortunately, some included studies used prophylactic treatment that is not in current (international) guidelines. The evidence for this improvement in quality of sleep is strong, and seems a generic effect of migraine prophylaxis.

Prophylactic treatment of FSGS recurrence in patients who relapsed in a previous kidney graft.

BACKGROUND AND HYPOTHESIS: Recurrence of focal segmental glomerulosclerosis (FSGS) is common after kidney transplantation and is classically associated with a significant decrease in graft survival. A major risk factor is a prior history of FSGS recurrence on a previous graft. This analysis reports the impact of a prophylactic treatment of FSGS recurrence in very high-risk patients who experienced a recurrence on a previous graft. METHODS: We performed a retrospective multicentre observational study in 25 French transplantation centres. The inclusion criteria were patients aged more than 18 years who had undergone kidney transplant between December 31, 2004, and December 31, 2020, and who had a history of FSGS recurrence on a previous graft. RESULTS: We identified 66 patients: 40 received prophylactic treatment (PT+), including intravenous cyclosporine and/or rituximab and/or plasmapheresis, and 26 did not receive any prophylactic treatment (PT-). The time to progression to end-stage kidney disease was similar between groups. The PT + group was younger at FSGS diagnosis and at the time of kidney retransplantation and lost their previous graft faster. The overall recurrence rate was 72.7% (76.9% in the PT- group and 70.0% in the PT + group, P = 0.54). At least partial remission was achieved in 87.5% of patients. The 5-year graft survival was 67.7% (95% CI: 53.4 to 78.4%): 65.1% (95%CI: 48.7 to 77.4%) in patients with FSGS recurrence vs. 77.3% (95% CI: 43.8 to 92.3%) in patients without recurrence (P = 0.48). CONCLUSION: Our study suggests that prophylactic treatment should not be used routinely in patients receiving a second transplantation after recurrence of FSGS on a previous graft. The recurrence rate is high regardless of the use of prophylactic treatment. However, the 5-year graft survival remains satisfactory.

Napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura: a randomized controlled trial. / æž•é¡¹éƒ¨åŸ‹çº¿æ³•è”åˆé ’çŸ³é ¸ç¾Žæ‰˜æ´›å°”ç‰‡é¢„é˜²æ€§æ²»ç–—æ— å ˆå †åå¤´ç—›ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the efficacy of napex acupoint thread-embedding combined with metoprolol tartrate tablet for prophylactic treatment of migraine without aura, and to compare its efficacy with simple napex acupoint thread-embedding and simple metoprolol tartrate tablet. METHODS: A total of 105 patients with migraine without aura were randomized into a combination group (35 cases, 5 cases dropped out), a thread-embedding group (35 cases, 4 cases dropped out) and a western medication group (35 cases, 2 cases dropped out). In the thread-embedding group, napex acupoint thread-embedding was applied at bilateral Fengchi (GB 20) and points of 1.5 cun nearby to the lower edge of spinous process of cervical 2. In the western medication group, metoprolol tartrate tablet was given orally, 12.5 mg a time, twice a day. In the combination group, napex acupoint thread-embedding combined with oral metoprolol tartrate tablet was delivered. The treatment of 8 weeks was required in the 3 groups. The days of headache attacks, frequency of headache attacks, headache severity (visual analogue scale [VAS] score) and the migraine specific quality of life questionnaire version 2.1 (MSQ) score were observed during baseline period (4 weeks before treatment to before treatment), observation period (1-4 weeks and 5-8 weeks in treatment) and follow-up period (1-4 weeks after treatment completion) respectively, the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% were calculated, and the safety was evaluated in the 3 groups. RESULTS: During the observation period and the follow-up period, the days of headache attacks, frequency of headache attacks and headache VAS scores in the 3 groups were reduced compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the days of headache attacks and the frequency of headache attacks in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05); during the observation period (1-4 weeks in treatment), the headache VAS scores in the combination group and the thread-embedding group were lower than that in the western medication group (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the headache VAS scores in the combination group were lower than those in the thread-embedding group and the western medication group (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were increased compared with those of the baseline period (P<0.05); during the observation period (5-8 weeks in treatment) and the follow-up period, the role prevention scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05); during the follow-up period, the emotion function scores of MSQ in the thread-embedding group and the western medication group were increased compared with those of the baseline period (P<0.05). During the observation period and the follow-up period, the scores of role restriction, role prevention and emotion function of MSQ in the combination group were higher than those in the thread-embedding group and the western medication group (P<0.05). There was no statistical difference in the proportions of the days of headache attacks/frequency of headache attacks relieved by 50% among the 3 groups (P>0.05), and there were no serious adverse reactions in the 3 groups. CONCLUSIONS: Napex acupoint thread-embedding combined with metoprolol tartrate tablet, simple napex acupoint thread-embedding and simple metoprolol tartrate tablet all can reduce the days of headache attacks and the frequency of headache attacks, relieve headache severity and improve the quality of life in patients with migraine without aura. Napex acupoint thread-embedding combined with metoprolol tartrate tablet has a better effect.

Amphotericin B in the Era of New Antifungals: Where Will It Stand?

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB's traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB's broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB's efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB's standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

Reliability, validity, and responsiveness of the Arabic version of HIT-6 questionnaire in patients with migraine indicated for preventive therapy: A multi-center study.

BACKGROUND: The Headache Impact Test (HIT-6) is an important patient-reported outcome measure (PROM) in migraine prevention trials. OBJECTIVES: This study aimed to (i) assess the reliability and validity of the Arabic version of HIT-6 in Arabic-speaking patients experiencing migraine, and (ii) evaluate the responsiveness of HIT-6 following migraine preventive therapy. METHODS: In this prospective study, patients with migraine (n = 145) were requested to fill out a headache diary, the Arabic version of HIT-6, and Migraine Disability Assessment Scale (MIDAS) at two time points (baseline and 3 months after initiation of prophylactic treatment). Some respondents (n = 73) were requested to fill out HIT-6 again 1 week from the baseline for test-retest reliability. The intensity of migraine headache attacks was evaluated using the Visual Analogue Scale (VAS). An anchor-based method was used to establish the minimal important change (MIC) value and responsiveness of HIT-6. RESULTS: The total scores of HIT-6 were significantly correlated to a fair degree with MIDAS (r = 0.41), as well as VAS (r = 0.53), and monthly migraine days (r = 0.38) at the baseline while at the follow-up (after 3 months), the correlations were of moderate degree with MIDAS scores (r = 0.62) and monthly migraine days (r = 0.60; convergent validity). Reliability estimates of the Arabic HIT-6 were excellent (Cronbach's α = 0.91 at baseline and 0.89 at follow-up). The average measure interclass correlation coefficient (ICC) value for the test-retest reliability was 0.96 (95% confidence interval = 0.94-0.98, p < 0.001). The HIT-6 total score is sensitive to change, being significantly reduced after prophylactic treatment compared to before (effect size = 1.5, standardized response mean = 1.3). A reduction from baseline of 4.5 on HIT-6 showed the highest responsiveness to predict improvement with an area under the curve equal to 0.66, sensitivity of 80%, specificity of 45%, and significance at 0.021. Changes in the HIT-6 total score were positively correlated with changes in monthly migraine days (r = 0.40) and VAS scores (r = 0.69) but not with changes in the score of MIDAS (r = 0.07). CONCLUSION: The Arabic version of HIT-6 is valid, reliable, and sensitive to detect clinical changes following migraine prophylactic treatment with a MIC of 4.5 points.

Carvacrol prophylaxis improves clinical outcome and dampens apoptotic and pro-inflammatory immune responses upon Campylobacter jejuni infection of human microbiota-associated IL-10-/- mice.

Incidence rates of human Campylobacter jejuni infections are progressively increasing globally. Since the risk for the development of post-infectious autoimmune diseases correlates with the severity of the preceding enteritis and campylobacteriosis treatment usually involves symptomatic measures, it is desirable to apply antibiotic-independent compounds to treat or even prevent disease. Given its health-promoting including anti-inflammatory properties carvacrol constitutes a promising candidate. This prompted us to test the disease-alleviating including immune-modulatory effects of carvacrol prophylaxis in acute murine campylobacteriosis. Therefore, human gut microbiota-associated IL-10-/- mice were orally challenged with synthetic carvacrol starting a week before C. jejuni infection and followed up until day 6 post-infection. Whereas carvacrol prophylaxis did neither affect gastrointestinal pathogen loads, nor the human commensal gut microbiota composition, it improved the clinical outcome of mice, attenuated colonic epithelial cell apoptosis, and dampened pro-inflammatory immune responses not only in the intestinal tract but also in extra-intestinal organs including the liver and the spleen. In conclusion, our preclinical placebo-controlled intervention study provides convincing evidence that oral carvacrol pretreatment constitutes a promising option to mitigate acute campylobacteriosis and in turn, to reduce the risk for post-infectious complications.

Risk Factors of Cetuximab-Induced Hypomagnesemia and the Effect of Magnesium Prophylaxis in Patients with Head and Neck Cancer: A Retrospective Study.

Hypomagnesemia is a characteristic adverse event of cetuximab in patients with head and neck cancer (HNC). However, there is limited information about its prevalence, risk factors, and preventive strategies. This study aimed to investigate the risk factors of hypomagnesemia and examine the preventive effects of prophylactic magnesium (Mg) administration. We initially investigated HNC patients treated with cetuximab between 2013 and 2019. Our institute started prophylactic Mg treatment (20-mEq Mg sulfate administration before cetuximab) in practice during this period. We retrospectively assess the preventive efficacy by comparing patients before and after its implementation. In total, 109 patients were included. In 60 patients without prophylaxis, all-grade and grade ≥2 hypomagnesemia at 3 months occurred in 61.7 and 15.0% of patients. The incidence of hypomagnesemia was not affected by regimens and concomitant medications. In 49 patients treated with prophylactic Mg treatment, there was no significant decrease in the cumulative incidence of hypomagnesemia. However, the preventive Mg treatment eliminated the need for additional Mg repletion to maintain Mg levels in patients treated with paclitaxel + cetuximab. A risk factor in patients without prophylaxis was a low Mg level at pre-treatment (≤2.0 mg/dL) (odds ratio: 6.03, 95% confidence interval: 1.78-20.4, p = 0.004), whereas that in patients with prophylaxis was the number of cetuximab doses (≥10) (odds ratio: 5.50, 95% confidence interval: 1.52-19.87, p = 0.009). In conclusion, a low pre-treatment Mg level was the only risk factor that could be avoided by prophylactic Mg administration. This preventive intervention is recommended for managing cetuximab-induced hypomagnesemia.

Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological cause of coronavirus disease 2019 (COVID-19) and continues to be a major health concern worldwide. Strategies to protect individuals at high risk of COVID-19 are critical but are currently a largely unmet need. We evaluated the oral antiviral drug ensitrelvir, which specifically targets the SARS-CoV-2 3CL protease, for its efficacy as a pre-exposure prophylactic treatment. Aged BALB/c mice were subcutaneously treated with various doses of ensitrelvir 24 h prior to a lethal SARS-CoV-2 challenge infection. Mouse body weight changes, survival rates, and viral titers in the lungs were evaluated, and plasma concentrations of ensitrelvir were determined. A single subcutaneous administration of ensitrelvir at 64 mg/kg or greater 24 h prior to SARS-CoV-2 challenge infection significantly protected aged mice against lethality and inhibited body weight loss. Pharmacokinetic analysis of ensitrelvir in the aged mice suggested that plasma concentrations ≥2.99 µg/mL resulted in a significant prophylactic effect against SARS-CoV-2 infection. In the aged mouse prophylaxis model, SARS-CoV-2 titers were suppressed in the lungs of mice treated with ensitrelvir 24 h prior to challenge infection, suggesting that the prophylactic administration of ensitrelvir exerted its prophylactic effect by suppressing viral proliferation. These findings suggest that ensitrelvir is a candidate drug for pre-exposure prophylactic treatment of individuals at high risk of COVID-19.

Prophylactic Oral Application of Activated Charcoal Mitigates Acute Campylobacteriosis in Human Gut Microbiota-Associated IL-10-/- Mice.

The incidence of human Campylobacter jejuni infections is increasing worldwide. It is highly desirable to prevent campylobacteriosis in individuals at risk for severe disease with antibiotics-independent non-toxic compounds. Activated charcoal (AC) has long been used as an anti-diarrheal remedy. Here, we tested the disease-mitigating effects of oral AC versus placebo in human gut microbiota-associated (hma) IL-10-/- mice starting a week prior to C. jejuni infection. On day 6 post-infection, the gastrointestinal C. jejuni loads were comparable in both infected cohorts, whereas campylobacteriosis symptoms such as wasting and bloody diarrhea were mitigated upon AC prophylaxis. Furthermore, AC application resulted in less pronounced C. jejuni-induced colonic epithelial cell apoptosis and in dampened innate and adaptive immune cell responses in the colon that were accompanied by basal concentrations of pro-inflammatory mediators including IL-6, TNF-α, IFN-γ, and nitric oxide measured in colonic explants from AC treated mice on day 6 post-infection. Furthermore, C. jejuni infection resulted in distinct fecal microbiota shift towards higher enterobacterial numbers and lower loads of obligate anaerobic species in hma mice that were AC-independent. In conclusion, our pre-clinical placebo-controlled intervention study provides evidence that prophylactic oral AC application mitigates acute murine campylobacteriosis.