Treatment Options Research Articles

Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses

BackgroundColorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research.ResultsHere, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response.ConclusionIt appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

Management of Neonatal Hepatic Hemangiomas: A Single-Center Experience Focused on Challenging Cases

Background: Management of hepatic hemangioma (HH) in infancy ranges from close monitoring to surgical resection. We analyzed the clinical characteristics and outcomes of HH according to its treatment options, with particular focus on challenging cases. Methods: Data of patients diagnosed with HHs in their first year of life and followed up for at least 1 year were retrospectively reviewed and divided into treatment and observation groups. Serial imaging results, serum alpha-fetoprotein (AFP) levels, medications, and clinical outcomes were compared. The detailed clinical progress in the treatment group was reviewed separately. Results: A total of 87 patients (75 in the observation group and 12 in the treatment group) were included. The median HH size at the initial diagnosis and the maximum size were significantly larger in the treatment group than the observation group (2.2 [0.5–10.3] cm vs. 1.0 [0.4–4.0] cm and 2.1 [0.7–13.2] vs. 1.1 [0.4–4.0], respectively; all p < 0.05]. The median initial and last serum AFP levels were significantly higher in the treatment group than in the observation group (76,818.7 vs. 627.2 and 98.4 vs. 8.7, respectively; all p < 0.05). Serum AFP levels in both groups rapidly declined during the first 3 months of life and were almost undetectable after 6 months. Among the challenging cases, a large (14 × 10 × 6.5 cm sized) focal HH was successfully treated using stepwise medical-to-surgical treatment. Conclusions: Patients with large HH and mild symptoms can be treated using stepwise pharmacotherapy. More aggressive surgical treatment of tumors unresponsive to initial pharmacotherapy may help shorten the treatment period and improve outcomes.

A modified technique for simplifying full-arch screw-retained implant rehabilitation with rapid digital conversion: a case report.

In this case report, a novel technique is described for an efficient, simple, and effective digital approach to immediate provisionalization of the implant-supported full-arch prosthesis. Today's patient population is increasingly educated about treatment options and expects efficient, esthetic, and comfortable results. This novel technique delivers on these aims while eliminating the many challenges posed by previously described digital and analog techniques to the immediate provisionalization of the implant- supported full-arch prosthesis. This technique requires minimal chair time and cost to the provider and reduces patient discomfort and complication risk. Combining the best features of analog and digital methods to conversion of the implant-supported full-arch, this novel method presents a promising new protocol for this popular procedure.

Focal Cortical Dysplasia: Diagnosis, Classification, and Treatment Options

AbstractFocal cortical dysplasias (FCDs) include a spectrum of anomalies of cortical development that consist in one or more areas with altered lamination and in some cases, neurons of abnormal morphology. Clinically, these structural anomalies led to arise of epilepsy, which is more often a focal, drug-resistant type with onset in pediatric or adolescent age. Occasionally, other symptoms have been reported in patients with FCDs, such as headache, movement disorders, and cognitive impairment. According to International League against Epilepsy scheme of 2011, three main subtypes of FCD can be distinguished, based of anatomopathological feature, radiological signs, and clinical expression. Magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography, and neurophysiology are the cornerstones of diagnosis, although their negativity cannot exclude FCD in symptomatic patients, especially in FCD type I which often is elusive. In MRI, the main finding is the irregularity of the cortical–subcortical signal, specifically reduction of cortical thickness and absence of clear demarcation between gray and white matters, which is strongly diagnostic for FCD. Epilepsy related to FCD is difficult to manage and until now there is not a clear direction for treatment's rules. FCD shows poor response to antiepileptic drugs (AEDs), and there is no evidence of some AED that has proved more efficacy than others in patients with FCDs. Considering genetical and pathophysiological recent acquisitions, mammalian target of rapamycin inhibitors may play a fundamental role in future treatment of FCDs, but nowadays, surgery still remains the main weapon, with 50% of patients who undergo neurosurgery.

Biomedical Applications of Cold Atmospheric Plasma: Cancer Therapy and Virus Inactivation

Cold atmospheric plasma (CAP), known for its ability to generate Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS), has emerged as a promising tool in many biomedical applications, including cancer therapeutics and virus inactivation. In cancer therapy, ROS and RNS induced by plasma have been shown to selectively target cancer cells, triggering apoptosis and inhibiting tumor growth while sparing healthy cells. This selective cytotoxicity makes plasma an attractive option for localized cancer treatment with minimal side effects. Additionally, the antimicrobial properties of ROS and RNS make plasma an effective agent for virus inactivation. By connecting the dots between cancer therapy and virus disinfection, this review paper sheds light on the potential of plasma-generated ROS and RNS as versatile tools in medical applications, offering a dual benefit of targeted cancer treatment and effective virus control. Specifically, this review explores the effects of CAP treatment on B16 melanoma cells, assessing changes in cell viability, proliferation, apoptosis and oxidative stress response. Dichloroacetate (DCA), a mitochondrial modulator, has shown promise in inducing apoptosis in melanoma cells. However, its clinical use is limited by side effects related to its neurotoxicity and suspected carcinogenicity. The potential of CAP in enhancing the therapeutic efficacy of DCA on B16-F10 melanoma apoptosis is also explored. CAP therapeutics for other types of cancers are also explored in this review. Alongside its implications in oncology, CAP has gathered substantial attention for its extraordinary potential in neutralizing viruses. CAP’s exceptional precision in targeting viral envelopes, genetic material and structural components disrupts their integrity and vital functions. This orchestrated mechanism offers a swift and efficacious route to render viruses inactive, encompassing both enveloped and nonenveloped viral types. In parallel pursuit, this review examines CAP-generated reactive species’ proficiency in deactivating SARS-CoV-2 across various surfaces. The inquiry entails subjecting surfaces to CAP treatment, succeeded by quantifying viral load and scrutinizing viral integrity. The outcomes gleaned from these investigations provide pivotal insights into CAP’s potential as a robust surface disinfection strategy, poised to combat the propagation of viral transmission.

Value-Based Health Care for Prostate Cancer Centers by Implementing Specific Key Performance Indicators Using a Balanced Score Card

Background: Prostate cancer (PC) is the most common cancer in men in 112 countries, and accounts for 15% of cancers. Because it cannot be prevented, the rise in cases is inevitable, and improvements in diagnostic pathways and treatments are needed, as there is still a shortage of cost-effective diagnostics and widespread oncologically safe treatment options with measurable quality. As part of the implementation of a Full Cycle of Care, instruments have been developed to achieve value-based medicine, such as consistent commitment to measurability. One of these instruments is the Balanced Scorecard (BSC). Here, we propose the first BSC for prostate cancer (PC) treatment. Methods: BSCs are used to assess performance in healthcare organizations across four dimensions: financial, patient and referrer, process, and learning and development. This study aimed to identify Key Performance Indicators (KPIs) for each perspective. A systematic literature search was conducted according to PRISMA guidelines using multiple databases and specific search terms to identify KPIs for PC care, excluding case reports and conference abstracts. In total, 44 reports were included in analyses and development of the PC-specific BSC. Results: In the present study, a PC-specific BSC and KPIs were defined for the four classic perspectives, as well as for a newly developed PC-Specific Disease and Outcome perspective, including patient-related parameters from the German Cancer Society and the International Consortium for Health Outcomes Measurement. In addition, the Process perspective includes KPIs of fulfillment of continuing education of residents and the metrics of structured training of the radical prostatectomy procedure in the Learning and Development perspective. Conclusions: The developed BSC provides a comprehensive set of perspectives for an Integrated Practice Unit or center in PC care, ensuring that the indicators remain manageable and applicable. The BSC facilitates value creation in line with Porter’s Full Cycle of Care by systematically collecting and providing economic, personnel, and medical results, actions, and indicators. In particular, this BSC includes KPIs of structured training of practitioners and metrics of the German Cancer Society, that recently proved to improve PC patients outcomes.

Ambient floor vibration sensing advances the accessibility of functional gait assessments for children with muscular dystrophies

Muscular dystrophies (MD) are a group of genetic neuromuscular disorders that cause progressive weakness and loss of muscles over time, influencing 1 in 3500–5000 children worldwide. New and exciting treatment options have led to a critical need for a clinical post-marketing surveillance tool to confirm the efficacy and safety of these treatments after individuals receive them in a commercial setting. For MDs, functional gait assessment is a common approach to evaluate the efficacy of the treatments because muscle weakness is reflected in individuals’ walking patterns. However, there is little incentive for the family to continue to travel for such assessments due to the lack of access to specialty centers. While various existing sensing devices, such as cameras, force plates, and wearables can assess gait at home, they are limited by privacy concerns, area of coverage, and discomfort in carrying devices, which is not practical for long-term, continuous monitoring in daily settings. In this study, we introduce a novel functional gait assessment system using ambient floor vibrations, which is non-invasive and scalable, requiring only low-cost and sparsely deployed geophone sensors attached to the floor surface, suitable for in-home usage. Our system captures floor vibrations generated by footsteps from patients while they walk around and analyzes such vibrations to extract essential gait health information. To enhance interpretability and reliability under various sensing scenarios, we translate the signal patterns of floor vibration to pathological gait patterns related to MD, and develop a hierarchical learning algorithm that aggregates insights from individual footsteps to estimate a person’s overall gait performance. When evaluated through real-world experiments with 36 subjects (including 15 patients with MD), our floor vibration sensing system achieves a 94.8% accuracy in predicting functional gait stages for patients with MD. Our approach enables accurate, accessible, and scalable functional gait assessment, bringing MD progressive tracking into real life.

Transarterial Embolisation of Abdominal Aortic Type II Endoleaks Accessed via the Deep Circumflex Iliac Artery: A Case Series and Literature Review.

We report our technique and experience treating 3 patients with native abdominal aortic aneurysm (AAA) sac expansion following EVAR, who were managed with transarterial embolisation via the deep circumflex iliac artery (DCIA). In this case series, we demonstrate that transarterial embolisation via the DCIA is a feasible and safe treatment option. The DCIA should be routinely interrogated with angiography as not only a cause of possible Type II endoleak, but also to identify a potential access route to the abdominal aortic sac for interventional treatment.

Unmet Needs and Treatment Preference of Systemic Treatments for Moderate-to-Severe Psoriasis from the Perspectives of Patients and Dermatologists in China.

The treatment options for moderate to severe psoriasis (msPsO) in China have been greatly increased with the approvals of biologics. However, the unmet needs and treatment preferences of systemic treatments for msPsO in China remain unclarified. Fifty dermatologists and 300 patients with msPsO (41% with severe psoriasis) were surveyed for effectiveness, safety, treatment convenience, and treatment preferences (using a choice-based conjoint questionnaire). Descriptive statistics and conjoint simulation analyses were employed to summarize survey information and assess treatment preferences. Both patients and dermatologists reported shorter treatment duration for oral drugs (2.7-6.2months) than that for biologics (9.5-17.0months). The most frequently reported treatment discontinuation reasons by the surveyed patients and dermatologists were unsatisfactory effectiveness (average 84.5%) for oral drugs and loss of efficacy over time (average 68.5%) for biologics. Commonly reported treatment inconveniences included regular lab tests for traditional oral drugs (average 71.5%) and administration assistance for biologics (average 58.0%). Injection site reactions (average 51.5%) and needle fear (average 35.5%) were frequently reported for biologics among the surveyed patients and dermatologists. Once-daily oral treatment was preferred over biweekly subcutaneous injection treatment when the two had comparable attributes (average in patients 87.1% vs. 12.9%; average in dermatologists 93.4% vs. 6.6%). Unmet needs of systemic treatments remain for msPsO in China. Once-daily oral treatment is preferred over biweekly subcutaneous injections to treat msPsO when other treatment attributes are comparable.

Biomimetic hydrogels with mesoscale collagen architecture for patient-derived tumor organoids culture

Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 μm and a mean diameter of 5 ± 1.5 μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.

EFFECTIVENESS OF CBT BASED RELAPSE PREVENTION THERAPY IN REDUCING RELAPSE RISK AND CRAVING AMONG INDIVIDUALS WITH SUBSTANCE USE DISORDER

Present study explored the effectiveness of Cognitive Behavioral Therapy with Relapse Prevention Techniques (CBT-BRPT) in reducing relapse risk and craving among individuals with substance use disorder (SUD). Drawing from a comprehensive literature review, the study addressed the pressing need for evidence-based interventions to combat SUD and its associated challenges. Present study employed a Pre-Experimental Research Design with a one-group pretest-posttest approach, utilized the purposive sampling to recruit a sample of 50 male participants seeking treatment for SUD. The instruments utilized include the Stimulant Relapse Risk Scale (SRRS), the Brief Substance Craving Scale (BSCS), and a Demographic Information Form. Results demonstrated significant reductions in both craving and relapse risk among participants who received CBT-BRPT intervention. These findings underscore the importance of CBT-BRPT as a viable treatment option for individuals with SUD, offering promising implications for clinical practice and substance abuse treatment programs. Despite limitations such as sample size and absence of a control group, the study's findings advocate for the integration of CBT approaches into existing treatment modalities and call for further research to validate the efficacy of CBT interventions in addressing substance use disorders comprehensively.

Functional Characterization of a Spectrum of Genetic Variants in a Family with Succinic Semialdehyde Dehydrogenase Deficiency

Succinic semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme involved in the catabolism of the neurotransmitter γ-amino butyric acid. Pathogenic variants in the gene encoding this enzyme cause SSADH deficiency, a developmental disease that manifests as hypotonia, autism, and epilepsy. SSADH deficiency patients usually have family-specific gene variants. Here, we describe a family exhibiting four different SSADH variants: Val90Ala, Cys93Phe, and His180Tyr/Asn255Asp (a double variant). We provide a structural and functional characterization of these variants and show that Cys93Phe and Asn255Asp are pathogenic variants that affect the stability of the SSADH protein. Due to the impairment of the cofactor NAD+ binding, these variants show a highly reduced enzyme activity. However, Val90Ala and His180Tyr exhibit normal activity and expression. The His180Tyr/Asn255Asp variant exhibits a highly reduced activity as a recombinant species, is inactive, and shows a very low expression in eukaryotic cells. A treatment with substances that support protein folding by either increasing chaperone protein expression or by chemical means did not increase the expression of the pathogenic variants of the SSADH deficiency patient. However, stabilization of the folding of pathogenic SSADH variants by other substances may provide a treatment option for this disease.

Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer’s Disease

Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases—dementia, type 2 diabetes, hypertension, Parkinson’s disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes—PSEN1, PSEN2, MAPT, APP, APOE, NOTCH, and HFE—for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene–drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases.

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study

BackgroundImmuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development.MethodsThis retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs.ResultsOur study included 181 patients (median age: 82 years, range: 80–94), mostly men (73%), with a performance status of 0–1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/μL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118.ConclusionIO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

Efficacy and Safety of Insulin Pump Therapy in Children and Adolescents with Type 1 Diabetes Mellitus

Continuous subcutaneous insulin infusion (CSII) pump represents a treatment option that can aid in achieving an important goal to reduce the most frequent complications associated with treatment; hypoglycemic and hyperglycemic episodes, which have also a great impact on life quality of patients. This study was conducted to report the effect and safety of insulin pump therapy on glycemic control, hypoglycemia and diabetic ketosis (DKA) rates in Libyan type 1 diabetic (T1D) patients. A descriptive and retrospective study which included patients treated and followed up at Tripoli University Hospital. Fifty-seven T1D patients used CSII pump enrolled in this study. Assessment of hypoglycemia, DKA, measuring the glycosylated hemoglobin (HbAlc) values at time of diagnosis (prior to CSII) and at time of study conduction. Mean age was 12.72 year ± 3.8 SD. Mean duration of diabetes was 7.28 years ± 3.9 SD. The baseline mean HbA1c was 8.58 ± 1.73% during Multiple Daily Injections (MDI) at pre-pump and 7.76 ± 1.33% post initiation of CSII (p = 0.001), with higher proportion of patient’s post-pump treated had good metabolic control with HbA1c compared to pre-pump infusion 23, 40.4% and 16, 28.1%, respectively. Both the incidence of ketoacidosis and severe hypoglycemic episodes was improved compared with MDI pre-pump significantly during CSII (P<0.001). This study supports that CSII is an effective alternative in managing T1DM. In addition, therapy with insulin pump in children with diabetes is very efficient and safe with obvious reduction of HbA1c and significantly diminished rates of DKA and hypoglycemia.

Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy.

Alzheimer's disease (AD), the leading cause of dementia, is characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. This condition casts a significant shadow on global health due to its complex and multifactorial nature. In addition to genetic predispositions, the development of AD is influenced by a myriad of risk factors, including aging, systemic inflammation, chronic health conditions, lifestyle and environmental exposures. Recent advancements in understanding the complex pathophysiology of AD are paving the way for enhanced diagnostic techniques, improved risk assessment, and potentially effective prevention strategies. These discoveries are crucial in the quest to unravel the complexities of AD, offering a beacon of hope for improved management and treatment options for the millions affected by this debilitating disease.

Treatment strategy for HER2-negative advanced gastric cancer: salvage-line strategy for advanced gastric cancer.

After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer.

A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.

Neurological disorders, including Alzheimer and Parkinson's, pose significant challenges to public health due to their complex etiologies and limited treatment options. Recent advances in research have highlighted the intricate bidirectional communication between the gut microbiome and the central nervous system (CNS), revealing a potential therapeutic avenue for neurological disorders. Thus, this review aims to summarize the current understanding of the pharmacological role of gut microbiome in neurological disorders. Mounting evidence suggests that the gut microbiome plays a crucial role in modulating CNS function through various mechanisms, including the production of neurotransmitters, neuroactive metabolites, and immune system modulation. Dysbiosis, characterized by alterations in gut microbial composition and function, has been observed in many neurological disorders, indicating a potential causative or contributory role. Pharmacological interventions targeting the gut microbiome have emerged as promising therapeutic strategies for neurological disorders. Probiotics, prebiotics, antibiotics, and microbial metabolite-based interventions have shown beneficial effects in animal models and some human studies. These interventions aim to restore microbial homeostasis, enhance microbial diversity, and promote the production of beneficial metabolites. However, several challenges remain, including the need for standardized protocols, identification of specific microbial signatures associated with different neurological disorders, and understanding the precise mechanisms underlying gut-brain communication. Further research is necessary to unravel the intricate interactions between the gut microbiome and the CNS and to develop targeted pharmacological interventions for neurological disorders.

Does the Subtalar or Tibiotalar Joint Need Fused in Primary Retrograde Tibiotalocalcaneal Nailing for Fragility Ankle Fractures?

As an alternative to traditional open reduction internal fixation of ankle fragility fractures, primary retrograde tibiotalocalcaneal (TTC) nailing has been investigated as a treatment option. These results suggest that this treatment is an acceptable alternative treatment option for these injuries. There are still questions about the need for formal joint preparation at the subtalar or tibiotalar joint when performing primary TTC nailing for fragility fractures. In this study, we retrospectively evaluated 32 patients treated with primary retrograde TTC nail without subtalar or tibiotalar joint preparation for a mean of 2.4 years postoperatively. We specifically reviewed the charts for nail breakages at either joint, patients developing subtalar or tibiotalar joint pathology requiring additional treatment, including return to the operating room for formal joint preparation. Fracture union occurred in 100% of patients. There were 3 cases (10.0%) of hardware failure, and 2 of these cases were asymptomatic and did not require any treatment. One patient (3.3%) developed hardware failure with nail breakage at the subtalar joint. This patient developed progressive pain and symptoms requiring revision surgery with formal arthrodesis of the subtalar and tibiotalar joint. This study shows that retrograde hindfoot nailing without formal subtalar or tibiotalar joint preparation is an acceptable potential treatment option in ankle fragility fractures. Mid-term follow-up demonstrates favorable outcomes without the need for formal joint preparation in this high-risk population. Comparative studies with higher patient numbers and long-term follow-up are needed to confirm the results of this study.Levels of Evidence: Level IV.

The efficacy of the use of atropine in children with reflex anoxic syncope during pallid breath-holding spells: can cardiac pacemaker implantation be avoided?

Reflex anoxic syncope is the result of an overreaction of the vagal system, resulting in hypotension and bradycardia or brief cardiac arrest. Because of the benign character and the absence of complications in short or long term, treatment is only necessary in case of frequent or severe clinical presentation. Treatment options are anticholinergic drugs or cardiac pacemaker placement. We investigated atropine treatment and aimed to examine if pacemaker placement can be avoided. We retrospectively reviewed patients treated with atropine for severe reflex anoxic syncope in our centre from January 2017 until May 2023, and compared our results to those in the literature. The study population consisted of 10 children, 70% female, with an age ranging from 5 months to 3 years (mean 14.5 months) when atropine treatment was started (dose 17-50 microg/kg/day). All patient's parents reported adequate symptom management during atropine treatment, with complete resolution in 10%. Minor side effects were reported in 60% (dry mucosa in 40%, obstipation in 20%, and nausea or blurry vision in 10%). We consider atropine a safe and effective treatment to manage reflex anoxic syncope with similar success rate to pacemaker implantation. However, pacemaker implantation entails substantial risk for complications (up to 25%) such as infection or technical problems and morbidity such as scar formation. This might be considered redundant for a benign and temporary condition, certainly given the possibility of other efficient treatment options. Consequently, we recommend atropine treatment over implantation of a cardiac pacemaker in children with severe reflex anoxic syncope.