Oral Therapy Research Articles

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

Practical surgical technique using the SMISS approach for lip reduction in involuted lip infantile hemangiomas

BackgroundLip infantile hemangiomas tend to show less volumetric regression and are more susceptible to visible sequelae in the involuted stage. Some of them still require surgical management after propranolol therapy. This study aimed to evaluate the efficacy and safety of the Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach applied to lip reduction for those with involuted lip hemangiomas.MethodsA retrospective review was performed to evaluate patients with lip hemangioma who received previous propranolol treatment and underwent the aforementioned procedure. Demographic characteristics, lesion morphology, and medical history were reviewed. The Visual Analog Scale was applied to assess the postoperative appearance. Complications within 12 months postoperatively were recorded.ResultsA total of 18 patients with lip hemangioma were eligible. All patients received oral propranolol therapy before surgery, with treatment duration ranging from 6.0 to 23.0 months. Their age at surgery ranged from 2.5 to 9.0 years. The median Visual Analog Scale scores were 8.0, ranging from 4.0 to 10.0. No severe complications were reported.ConclusionsThis modified technique based on the SMISS approach has proven reliable and effective in improving the aesthetic outcome for involuted lip infantile hemangiomas. Practical surgical techniques still play an important part in the propranolol era.

The Atrial FibriLlatiOn (FLOW-AF) Registry in the Middle East and North Africa: Patient Characteristics, Treatment Patterns and Outcomes.

Limited data on atrial fibrillation (AF) are available from the Middle East and North Africa region (MENA). The aim of the FLOW-AF registry was to evaluate the characteristics, treatment patterns, and clinical and economic outcomes ofpatients with newly diagnosed non-valvular atrial fibrillation (NVAF) in MENA. This multi-center, prospective, observational study (the FLOW-AF registry) enrolled patients newly diagnosed with NVAF across Egypt, Lebanon, Kingdom of Saudi Arabia, and United Arab Emirates. The data collection occurred at enrollment (baseline) and after 6- and 12-months (follow-up). Baseline data included demographics, AF characteristics, medical history, and anti-thrombotic treatment patterns. Clinical events, healthcare resource utilization, and direct costs were collected at follow-up. The study enrolled a total of 1418 patients (52.7% males and 47.3% females). The mean age of the patients was 64.5years and 90.6% were white. The mean (standard deviation) CHA2DS2-VASc and HAS-BLED risk scores were 2.7 (1.6) and 1.6 (1.2), respectively. Non-vitamin K antagonist oral anticoagulants, antiplatelet therapy, and vitamin K antagonists were prescribed to 65.8%, 16.4%, and 12.9% patients, respectively. During follow-up, the following rates of clinical outcomes were observed: bleeding events (1.7%), transient ischemic attack (1.7%), all-cause mortality (1.7%), stroke (0.6%), myocardial infarction (0.2%), and systemic embolism (0.08%). This MENA patient population was younger and had lower mean baseline CHA2DS2-VASc and HAS-BLED scores. The rates of clinical outcomes over 1-year in this study were low. Longer follow-up is required to comprehensively assess clinical outcomes in this patient population.

Smoking Impacts Alzheimer's Disease Progression Through Oral Microbiota Modulation.

Alzheimer's disease (AD) is an important public health challenge with a limited understanding of its pathogenesis. Smoking is a significant modifiable risk factor for AD progression, and its specific mechanism is often interpreted from a toxicological perspective. However, microbial infections also contribute to AD, with oral microbiota playing a crucial role in its progression. Notably, smoking alters the ecological structure and pathogenicity of the oral microbiota. Currently, there is no systematic review or summary of the relationship between these three factors; thus, understanding this association can help in the development of new treatments. This review summarizes the connections between smoking, AD, and oral microbiota from existing research. It also explores how smoking affects the occurrence and development of AD through oral microbiota, and examines treatments for oral microbiota that delay the progression of AD. Furthermore, this review emphasizes the potential of the oral microbiota to act as a biomarker for AD. Finally, it considers the feasibility of probiotics and oral antibacterial therapy to expand treatment methods for AD.

Inflammation‐Activated Endogenous Macrophage‐Mediated Prodrug Delivery System Overcoming Biological Barriers for Enhanced Oral Meningitis Therapy

AbstractSignificant health risks are posed by meningitis due to its rapid progression, and challenges are encountered in intravenous antibiotic administration, especially in crossing the blood‐brain barrier. To address this, an inflammation‐activated, endogenous macrophage (MΦ)‐mediated oral prodrug delivery system is developed for targeted therapeutic interventions in bacterial meningitis treatment. This system is guided by inflammation‐derived chemoattractants and triggers drug release through inflammation‐induced reactive oxygen species (ROS). Comprised of naturally derived β‐glucans conjugated with the antibiotic cefotaxime (CTX) using a ROS‐responsive linker, nanoparticles (βGlus–CTX NPs) are formed in aqueous solutions. In a mouse model of Klebsiella pneumoniae‐induced meningitis, orally administered βGlus–CTX NPs are traversed by intestinal microfold cells, surpassing the intestine‐epithelial barrier, and are absorbed by resident endogenous MΦ. These MΦ‐mediated drug delivery vehicles are then traveled through the lymphatic and circulatory systems, crossing the compromised blood‐brain barrier, ultimately reaching inflamed brain tissues, guided by their derived chemoattractants. In ROS‐rich inflamed tissue environments, the linkers in the βGlus–CTX NPs are cleaved, releasing therapeutic CTX for localized treatment. Targeted antibiotic treatment for bacterial meningitis is offered by this oral, endogenous MΦ‐mediated prodrug delivery system, overcoming the robust gut‐to‐brain biological barriers and potentially enhancing effectiveness for comfortable home‐based treatment.

Oral flecainide therapy and myocardial pacing: preliminary data from a prospective multicenter registry

Abstract Background Antiarrhythmic drugs, class I are widely used for prevention of atrial fibrillation recurrence. However, previous studies found that these drugs could affect pacing thresholds among pacemaker recipients. Aim of the study: evaluate short -term effect on myocardial pacing following therapy with oral flecainide (200 mg/daily). Methods 45 consecutive pacemaker recipients were prospectively enrolled in a multicenter registry. These patients had preserved left ventricular ejection fraction, a dual chamber pacemaker with symptomatic sustained high-rate atrial fibrillation episodes and stable output atrial and ventricular thresholds. Patients were followed with ambulatory and/or remote monitoring. Results mean age was 74±1 years, 48% pts were male and AF burden was 8±16%. Pacemaker implantation was performed 3.9±0.3 year before study enrollment. Three (6%) out of 45 patients were excluded due to drug sided effects including dyspnea (n=1), diplopia (n=1) and toxicity during acute renal insufficiency (n=1). Flecainide treatment was associated with a significant reduction of atrial fibrillation burden (from 8±16% to 5±12%, p&amp;lt;0.01). At 30 days follow-up since Flecainide starting therapy both atrial and ventricular sensing significantly decreased (3.6 ± 2.2 vs 3.4 ± 2.1mV p=0.01; 12.5±6.6 vs 11.8±6.3 mV p=0.01), while there was a slight increase of both atrial and ventricular capture thresholds (0.77±0.61V@0.4ms vs 0.80±0.42V@0.4ms p=0.01; 0.80±0.53V @0.4ms vs 0.83±0.33V @0.4ms p=0.01). No patient required pacemaker parameters reprogramming. Conclusions oral flecainide therapy among pacemaker recipients at 30 days follow-up seems to be safe and do not affect device function. Further studies with additional follow-up data are warranted.

Incidence and outcome of periinterventional atrial fibrillation in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention

Abstract Background Peri-interventional atrial fibrillation (AF) may be detected in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Data on the thromboembolic risk and long-term clinical outcome in patients with AF limited to the peri-interventional period is scarce. Purpose To assess the incidence and impact on long-term clinical outcome of peri-interventional de-novo AF in STEMI patients. Methods and Results This retrospective single-center cohort study included all patients who underwent PCI between January 2016 and November 2020 (n=491) due to STEMI. Patients were stratified to three cohorts of AF status: Pre-existing AF: n=42 [8.6%], newly diagnosed peri-interventional AF: n=56 [11.4%] and no AF: n=393 [80.0%]. Patients with newly diagnosed peri-interventional AF as well as patients with pre-existing AF had in median a mild-moderately reduced left ventricular ejection fraction (LVEF), patients in sinus rhythm in median a normal LVEF. During the average follow-up time of 4.7 years (min. 2 years, max. 7 years) the rate for readmission for AF or occurrence of AF without hospital admission was increased in patients with peri-interventional de-novo AF or pre-existing AF (n=6 [10.7%], n=10 [23.8%]) compared to those in sinus rhythm n=22 [5.6%] (p&amp;lt;0,001) The occurrence of ischemic stroke was higher in patients with peri-interventional de-novo AF (n=2 [3.6%] or with pre-existing AF (n=2 [4.8%]) compared to those in sinus rhythm (n=6 [1.5%]. (p=0.256) The risk of cardiovascular death was significantly higher in patients with newly diagnosed peri- interventional AF compared to patients with pre-existing or no AF (n=13 [23.2%], n=5 [11.9%], n= 37 [9.4%]) (p=0.009). In the patient group with peri-interventional de-novo AF, only 25.0% (n=13) received long-term oral anticoagulation therapy (OAK). The rate of stroke in patients who received OAK after peri- interventional de-novo AF was 7.7% (n=1) compared to those without OAK 2.6% (n=1). Conclusion Peri-interventional AF is a frequent finding in STEMI patients undergoing primary PCI. Patients with peri-interventional AF had a significantly increased risk for an adverse cardiovascular outcome. Optimal secondary prophylactic measures appear mandatory in this patient population. The significance of long-term OAK therapy is to be determined.

Patient-reported treatment burden: comparison between vitamin-K antagonist and non-vitamin K antagonist oral anticoagulants

Abstract Introduction Treatment burden (TB) is defined as the overall workload that maintenance or improvement of their functioning and well-being poses on patients with chronic medical conditions. A high patient-reported TB has been associated with lower adherence to treatment and increased risk of major adverse events including death. We explored the differences in patient-reported TB value and prevalence of unacceptably high TB score (≥59 points) between patients receiving vitamin K antagonist oral anticoagulants (VKA) and non-vitamin K antagonist oral anticoagulants (NOAC). Furthermore, we explored contributory factors associated with TB and the relationship between TB and quality of life (QoL) in these patients. Methods A single-centre study included consecutive adult in- and outpatients on long-term oral anticoagulation, seen at a university clinical centre a from April to June 2019, who were willing to complete the Treatment Burden Questionnaire encompassing 13 items assessing the TB associated with taking medicine, self-monitoring, laboratory assessments, medical consultations, organisational and administrative requirements, adherence to dietary and physical activity recommendations, as well as the social repercussions of the treatment. Results Of 320 enroled patients, 206 (64.4%) were taking a VKA. Atrial fibrillation was the most common indication for long-term oral anticoagulation (n=299, 93.4%). The mean TB score was significantly higher in patients on VKA versus those taking a NOAC (48.8 ±26.5 vs. 41.8 ±19.7, P= 0.014), mostly owing to significantly higher TB values for questions related to self-monitoring, including the International Normalized Ratio (INR) control (3.85±3.32 vs. 1.62±1.38, P&amp;lt;0.001) and diet restrictions (3.98±3.43 vs. 2.48±2.49, P&amp;lt;0.001) in patients taking VKA (Figure 1). In addition, these patients significantly more often reported an unacceptably high TB of ≥59 points compared with those taking NOAC (30.1% vs 18.4%, P= 0.024). Multivariable regression analysis of predictors of TB in patients taking a VKA or NOAC are presented in Table 1. Conclusion In our study, patients receiving a VKA reported significantly higher TB compared to those using NOAC, especially regarding the questions about self-monitoring (including INR control) and diet restrictions. An unacceptably high TB was also more prevalent among patients receiving a VKA. Our findings suggest that prescribing NOACs in preference to VKAs could help in decreasing the self-reported TB in patients who need oral anticoagulant therapy.

Comparison of oral versus intranasal methylcobalamin in patients of tinnitus

Background: Tinnitus is perception of sound in the absence of an external auditory stimulus. It is an experience that originates from a cause or trigger in the cochlea, brainstem or at higher centres. Methods: A randomized, double-blinded pilot study was conducted, wherein a total of 64 patients were enrolled. Of which 32 were considered as Group A (oral methylcobalamin was administered) and 32 in Group B (intranasal methylcobalamin was administered). Group A patients enrolled randomly received oral methylcobalamin therapy (tablet methylcobalamin 500 mcg tablet once a day for a period of 6 weeks). Group B patients enrolled randomly received intranasal methylcobalamin treatment (nasal spray 500 mcg per day) for a period of 6 weeks. Results: A sum of 19 patients of the total patients included in the study were found to be Vitamin B12 deficient that is 42.1% were considered to be Vitamin B12 deficient when the normal levels were considered to be 250 pg/ml, which could be considered to be a significantly high prevalence. Patients having Vitamin B12 deficiency showed improvement in visual analogue scale score after vitamin B12 therapy. Conclusions: Supplementation of Vitamin B12 in vitamin B12 deficient patients having tinnitus has shown symptomatic improvement. However, no significant improvement in visual analogue scale scores in patients without B12 deficiency was observed. There was improvement in VAS in cobalamin-deficient patients receiving Vitamin B12 weekly for 6 weeks.

Temporal trends of ischemic stroke rates in atrial fibrillation without anticoagulation: a nationwide cohort study from 2007 to 2018

Abstract Background Atrial fibrillation (AF) is a major risk factor for ischemic stroke (IS), but whether the magnitude of this risk has changed over time is unknown. Purpose To evaluate temporal trends in IS rates in patients with AF who have not initiated oral anticoagulant (OAC) therapy. Methods The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study covers all patients with incident AF in Finland from 2007 to 2018. A four-week quarantine period from AF diagnosis was applied and only follow-up time without OAC therapy was included. IS incidence rates were computed in four-year intervals. Results In total, 129 789 patients with new-onset AF (49.2% women; mean age 71.4 years) were identified. The IS incidence rate trends according to sex and the CHA2DS2-VA score are depicted in the Figure, along with the previously estimated treatment thresholds for direct oral anticoagulants (red broken line) and warfarin therapy (blue broken line). Between the calendar year intervals of 2007-2010 and 2015-2018, their mean CHA2DS2-VA score increased from 2.5 to 3.0, while concurrently the overall IS rate decreased by 25% from 36.7 (95% CI 34.5-39.0) to 27.6 (95% CI 26.1-29.0) events per 1000 patient years. This trend was driven by a 32% decrease in women, particularly among those with high CHA2DS2-VA scores. The overall IS rate in patients with a CHA2DS2-VA score of 1 was 8.2 (95% CI 7.2-9.4) events per 1000 patient years and it remained stable across the study period. Conclusions The IS rates in AF patients without OAC therapy have decreased by 25% between 2007 and 2018, despite their rising stroke risk scores. In patients with a CHA2DS2-VA score of 1 the IS rate appears to be lower than previously assumed and approximately at the threshold at which the potential benefits and harms of OAC therapy have been estimated to overlap.

Obesity paradox in atrial fibrillation patients on oral anticoagulation therapy: a Korean nationwide cohort study

Abstract Background The obesity paradox is a phenomenon that has been observed in specific pathological conditions, wherein individuals who are overweight or obese exhibit a survival advantage over those with a normal weight. This phenomenon has also been noted in patients diagnosed with atrial fibrillation (AF), although the impact of body mass index (BMI) on clinical outcomes in AF patients undergoing oral anticoagulant (OAC) therapy remains uncertain. Purpose The aim of this study was to investigate the potential relationship between obesity and cardiovascular outcomes in patients diagnosed with AF who were receiving OAC. Methods We utilized administrative claims data from the Korean National Health Insurance Service and the combined health check-up database of the National Health Insurance Corporation to conduct a retrospective national cohort study spanning from 2013 to 2020. The patients newly prescribed OAC for AF were included, between January 2015 and December 2019. We followed up with patients from their index date until each outcome event or the end of the study period. BMI was categorized into 5 groups based on the World Health Organization's recommended criteria for Asian populations. The predefined clinical outcomes included thromboembolism, major bleeding, all-cause death, and the composite outcome. Results A total of 35,333 patients were included in the study. The mean age was 69 ± 10 years, and 37.1% were female. During a median follow-up of 2.0 years (IQR, 0.4–3.3), there were 11,634 thromboembolic events, 1,521 major bleeding events, and 2,586 deaths. The adjusted hazard ratio (HR) for thromboembolism, major bleeding, all-cause death, and a composite outcome were lower in obese II group (HR 0.79, 95% CI 0.73–0.86; HR 0.99, 95% CI 0.79–1.24; HR 0.75, 95% CI 0.62–0.91; HR 0.81, 95% CI 0.75–0.88) compared to the normal range BMI group. Conclusions In AF patients undergoing OAC therapy, individuals classified as obese exhibited a reduced risk of thromboembolism, major bleeding, all-cause mortality, and composite outcome compared to patients with normal weight.Adjusted hazard ratio of outcomes by BMI

Levodopa infusion therapies for Parkinson disease.

to review recent progress in the development and use of continuous levodopa therapies in Parkinson disease (PD). Levodopa/Carbidopa intestinal gel (LCIG) is a continuous levodopa therapy which is widely used in the United States, Europe and other countries and is effective at reducing 'off' time. Recent work has shown that LCIG can be useful in managing dyskinesias and can improve nonmotor symptoms and quality of life. Several studies have shown good long-term effectiveness of LCIG. Recent data support the cost-effectiveness of this treatment strategy. Subcutaneous (SC) delivery of levodopa is a newer strategy that avoids the need for a surgically placed gastric tube. Two different products enabling SC delivery of levodopa are in development: ND0612 and foslevodopa/foscarbidopa. Both have recently been shown to reduce 'off' time in randomized, double-blind trials. Adverse effects of SC levodopa are primarily related to skin reactions at the infusion site. Continuous levodopa therapies can be used to treat Parkinson disease motor fluctuations that cannot be managed with standard oral therapies. They may also improve nonmotor symptoms, and improve overall quality of life in patients with advanced PD.

#406 High ferritin is not needed in hemodialysis patients: a retrospective study of total body iron and oral iron replacement therapy

Abstract Background and Aims In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. Although serum ferritin is useful as an indicator of iron stores, it does not necessarily reflect body iron levels in HD patients with unstable hematopoiesis since iron metabolism is a semi-closed system in vivo. In this study, we investigated total body iron (TBI), new index calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. Method We analyzed data on 105 courses of low-dose iron replacement therapy (50–120 mg of iron daily) administered to 83 patients with serum ferritin &amp;lt;60 ng/mL and Hb &amp;lt;12 g/dL undergoing maintenance hemodialysis at our institution. Low-dose oral iron replacement therapy was initiated between August 2016 and June 2023 and continued for at least seven months. All blood samples were collected at the start of hemodialysis at the beginning of the week. Blood examinations were performed twice a month, and patients were given darbepoetin alfa (DA), long-acting ESAs to maintain Hb at the target level of 10–12 g/dL, in accordance with the guidelines of the Japanese Society for Dialysis Therapy. Iron-related parameters were determined based on blood samples collected once a month, with TSAT calculated from serum iron (Fe) and total iron-binding capacity (TIBC), using the following equation. TSAT=Fe/TIBC × 100. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7, in two groups of patients, namely, iron-therapy responders and non-responders. Furthermore, we investigated factors associated with steady-state TBI. TBI was regarded as achieving a steady state during the course of therapy when the trend shifted from an increase and the difference from the value at one month was less than or equal to zero. TBI was calculated using the formula proposed by Cable et al (Transfusion. 2016, 56, 2005). Results Mean age was 68.1±12.6 years and median time on hemodialysis was 6.6 years. Of the 105 courses of therapy, 75 were delivered to men and 30 to women, and 66.7% of the patients had diabetic nephropathy. The patients had a mean Hb level of 10.4±0.7 g/dL, a mean serum ferritin level of 27.3±12.5 ng/mL, mean transferrin saturation (TSAT) of 18.1%±5.9%, and a median C-reactive protein level of 0.1 mg/dL at the start of each course. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900±447 vs. 1900±408 mg, Fig. 1). As for RBC iron, iron-therapy responders showed significant monthly increases up to month 3, whereas non-responders showed constant values. Regarding iron stores, iron-therapy responders showed significant monthly increases up to month 5, while non-responders showed a significant increase only at month 1. DA per body weight showed a significant decrease at month 3 and 4 in the effective group, but a slight increase in the non-responder group. Steady-state TBI did not correlate with Hb or serum ferritin, but was strongly correlated with body surface area (BSA) using the Du Bois formula [TBI=−791.914 + 1628.606 × BSA (m2); R2=0.88, p&amp;lt;0.001, Fig. 2]. Conclusion This study showed that hemodialysis patients can increase their body iron levels during oral iron replacement therapy and maintain them at the same level after sufficiency has been achieved, suggesting activation of a “mucosal block.” Furthermore, this result also suggests that determining iron sufficiency based on serum ferritin alone is difficult in HD patients with fluctuations in Hb. However, regression equations using steady-state TBI and BSA showed a high degree of fit. Therefore, BSA might potentially be used in estimations of TBI sufficiency, which may be useful for avoiding excessive iron dosage.

#578 Calcium-channel blockers chyloperitoneum: an underrated complication in peritoneal dialysis

Abstract Background and Aims Bacterial peritonitis is the most feared complication for peritoneal dialysis (PD) patients. Together with abdominal pain and elevated white cell count in peritoneal effluent, the presence of a cloudy peritoneal effluent represents the main diagnostic criteria. The appearance of this last sign, even in an asymptomatic patient, always represents cause for concern and raises suspicion of an already subclinical peritonitis but can also represent other causes. Among acellular aetiologies for a cloudy peritoneal effluent, there is the presence of triglycerides, usually above 200 mg/dl, called chyloperitoneum, secondary to pancreatitis or concomitant calcium- channel blockers (CCBs) therapy. Most of dialysis patients are affected by hypertension. Considering the frequent necessity of limiting dosage of angiotensin 2 receptors blockers (ARB) and ACE inhibitors (ACE-I) for the risk of hyperkalaemia, CCBs frequently represent one of the most common prescribed antihypertensive drugs. Usually well tolerated and with limited adverse effects, literature demonstrates how they can induce, for not fully understood reasons (research supposed a role for the lipophilicity of these drugs, an impaired lymphatic absorption, an increased lympho-vascular dilatation or lymphatic hydrostatic pression) the presence of triglycerides in peritoneal effluent to levels causing chyloperitoneum. Frequently reported as anecdotical cases, especially in Asian studies, only limited information are available about influence of drug dosage or other concomitant therapies but is evident a higher frequency with lercanidipine assumption. Method We evaluated all patients undergoing peritoneal dialysis in our Centre in 2023. Chyloperitoneum (Fig. 1) diagnosis was obtained in cases of cloudy peritoneal effluent in asymptomatic patients with normal inflammatory indexes, normal white cell count on peritoneal effluent and negative cultural samples on peritoneal effluent associated with complete remission after fast peritoneal washes and reduction or discontinuation of CCBs. Results 16 patients underwent PD in our Centre during 2023: 4 automated (APD) and 12 ambulatory (CAPD). All of them were affected by hypertension and 10 of 16 (2 APD and 8 CAPD) were already in chronic therapy with CCBs (5 with lercanidipine, 4 with lacidipine and 1 with barnidipine), all at maximum accepted dosage. 4 patients presented during 2023 one or more episodes of cloudy peritoneal effluent without any sign or symptom of infection. All these patients were in CAPD and in therapy with lercanidipine and underwent to full remission after fast peritoneal washes; for 2 of them was necessary to discontinue CCBs therapy while for the other 2 dose reduction was fair. In 1 patient was recently associated oral anticoagulant therapy and in another 1 was recently associated dual antiplatelet therapy. None of these patients presented more episodes and all of them are still in PD. Among the other 8 patients in CCBs therapy without episodes of chyloperitoneum, only 1 was already in therapy with single antiplatelet therapy and none of them with double one or with oral anticoagulant. Conclusion cloudy peritoneal effluent is always cause for concern for Nephrologists since that it could represent, event without any other sign or symptom of infection, an already subclinical bacterial peritonitis. Most of dialysis patients are also affected by hypertension. Since usage of ARB and ACE-I is limited by risk of hyperkalaemia, CCBs represents one of the most prescribed antihypertensive drugs. For PD patients, however, the risk of chyloperitoneum must be considered since, even if it can be easily corrected, it could also affect therapy and patient management. Described in literature as only an anecdotical complication, our study shows that the incidence could be much higher and appears to be linked a specific molecule, lercanidipine, taken at higher dosage and to CAPD. Concomitant therapies as dual antiplatelet or oral anticoagulant therapy could represent a stimulating factor but other studies, with more numerous patients, are needed for further considerations.

Safety of Antiandrogens for the Treatment of Female Androgenetic Alopecia with Respect to Gynecologic Malignancies

The most common type of alopecia in women is female androgenetic alopecia (FAGA), characterized by progressive hair loss in a patterned distribution. Many oral therapies, including spironolactone (an aldosterone antagonist), androgen receptor blockers (e.g., flutamide/bicalutamide), 5-alpha-reductase inhibitors (e.g., finasteride/dutasteride), and oral contraceptives, target the mechanism of androgen conversion and binding to its respective receptor and therefore could be administered for the treatment of FAGA. Despite significant advances in the oral treatment of FAGA, its management in patients with a history of gynecological malignancies, the most common cancers in women worldwide, may still be a concern. In this review, we focus on the safety of antiandrogens for the treatment of FAGA patients. For this purpose, a targeted literature review was conducted on PubMed, utilizing the relevant search terms. To sum up, spironolactone seems to be safe for the systemic treatment of FAGA, even in high-risk populations. However, a general uncertainty remains regarding the safety of other medications in patients with a history of gynecologic malignancies, and further studies are needed to evaluate their long-term safety in patients with FAGA and risk factors to establish an optimal risk assessment and treatment selection protocol.

#1182 Arterial hypertension and chronic obstructive pulmonary disease—problems of choice of therapy

Abstract Background and Aims The development of hypertension in COPD is based on the early formation of endothelial dysfunction in the small and large circulatory circles, increased sympathetic activity with an imbalance in the synthesis of catecholamines, a violation of the role of the lungs in the metabolism of vasoactive substances, oxidative stress, chronic systemic inflammation, an imbalance in the renin-angiotensin-aldosterone system (RAAS). There are few studies confirming the role of RAAS components in the pathogenesis of cardiovascular changes in patients COPD. The activity of angiotensin converting enzyme (ACE) increases with hypoxia, which may play an important role in increasing the degree of systemic hypertension. An increase in the function of the RAAS is possible both under the direct influence of hypoxia and indirectly through activation of the sympathoadrenal system. To evaluate the efficacy and tolerability of the angiotensin II receptor antagonist valsartan (Nortivan) at a dose 80-160 mg per day in patients with hypertension of 1-2 degrees and COPD of stage II-IV. Method The study design is a local, open, incomparable study on the efficacy and safety of the drug Nortivan in patients with hypertension in combination with COPD. We examined 18 patients with stage II-IV in remission, suffering from grade I and II hypertension, determined in accordance with the generally accepted classification of blood pressure levels (VNOK, 2010). Results The criteria for exclusion from the study were the presence in patients of complications of hypertension, coronary heart disease, decompensated chronic pulmonary heart, endocrine diseases requiring drug correction, kidney pathology, chronic heart failure, oral steroid therapy. 10 days in the last 6 months before inclusion in the study, oncological diseases and any other conditions that could interfere with the interpretation and evaluation of the results of the study. Patients who had not previously received antihypertensive treatment were included in the study immediately, and the rest underwent a washing period for 2 weeks. Patients received Nortivan as antihypertensive therapy for 24 weeks. The effectiveness of therapy was controlled by daily monitoring blood pressure. The choice of quality criteria for the effectiveness of therapy parameters SMAD is associated with literature data and own observations on the prevalence of diurnal blood pressure profiles in patients with hypertension and COPD with no decrease or increase in blood pressure at night, when office blood pressure figures are to a lesser extent reflect the effectiveness of antihypertensive therapy. The initial dosage was 80 mg/day. With insufficient hypotensive effect, the dose of the drug was doubled at the 4th week of treatment. The basic COPD therapy did not change throughout the study period and included anticholinergic drugs (ipratropium bromide, tiotropium bromide), beta2-adrenomimetic (fe-noterol) or a combination thereof. Initially and after 24 weeks of treatment, a complete laboratory examination was performed: a clinical blood test, a biochemical blood test. The thickness of the intima-media complex of the carotid arteries and ECG was also studied. The criterion The safety of the therapy was assessed by the indicators of respiratory function, daily pulse oximetry. Conclusion The use of the drug Nortivan has shown high efficacy and safety in patients Grade I–II hypertension in combination with stage II-IV COPD. A statistically and clinically significant normalization of SMAD indicators with correction of pathological types of daily curves due to a decrease in the number of patients with an increase in or the absence of a decrease in blood pressure during the night period. The safety of using the drug in the clinical group with bronchial obstruction syndrome was confirmed by the dynamics of ventilation indicators according to spirometry and the results of daily pulse oximetry, which showed the absence of exacerbation of hypoxia during therapy.

#357 Sex differences in the aldosterone-renin system must be taken into account during screening for primary aldosteronism

Abstract Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P &amp;lt; 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P &amp;lt; 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P &amp;lt; 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120mg (+ 60mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20mg oral (+ 10mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12months post-randomisation or death, whichever occurs first. This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. Trial registered on Australian New Zealand Clinical Trials Registry. ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ±9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.

Role of Intravenous Iron in Current Era

Iron is an essential trace mineral necessary for life, and iron deficiency anaemia (IDA) is one of the most common haematological problems worldwide. Oral iron replacement therapy is a simple, inexpensive treatment option for the treatment of iron deficiency in stable patients, but there are many populations for whom IV iron is more effective. Therefore, IV iron should be considered when there are no contraindications, when poor response to oral iron is anticipated, when rapid hematologic responses are desired. Third generation intravenous (IV) iron therapies allow rapid and complete replacement dosing without the toxicity issues inherent with older iron preparations. This review provides an updated overview on diagnosis and management of IDA in patients with chronic conditions, preoperative and considers the properties of the different IV irons, and how differences might impact current and future clinical practice. We will discuss the benefits and limitations of oral versus intravenous iron replacement. Keywords: Anaemia; Intravenous Iron; Iron Deficiency; Oral Iron