First-line Therapeutic Option Research Articles

#2153 Difelikefalin: a new solution against itching in CKD-aP patients

Abstract Background and Aims Chronic kidney disease-associated pruritus (CKD-aP) is one of the most common and burdensome symptom affecting patients with advanced chronic kidney disease, with an estimated prevalence of 53.3%. The clinical presentation is extremely variable, from minor lesions to true scratch injuries, and significantly affects the patient's quality of life (QoL), sleep quality and mood, as well as being associated with increased mortality. At present, high-quality evidence on which to base treatment is limited. Currently proposed first-line therapeutic options include optimization of dialysis treatment, emollient agents, UVB light, antihistamines, gabapentin and pregabalin. Recently difelikefalin, a k-opioid receptor agonist, has been the first Food and Drug Administration (FDA) approved drug for moderate-severe CKD-aP treatment. The aim of our study is to demonstrate the efficacy of this drug in relieving symptoms in CKD-aP patients. Method For this preliminary retrospective observational study, 19 patients (9 females, 10 males) with CKD-aP performing dialysis at our Dialysis Center were recruited. All of them had appropriate Kt/V values and had previously been treated with first-line medications. The other main demographic and clinical characteristics of our population, such as calcium-phosphate metabolism and inflammation's indexes, can be seen in Table 1. Our population underwent the Worst Itch Numeric Rating Scale (WI-NRS) by which the presence, intensity, and impact on sleep of this symptom were investigated. They also were subjected to questions that investigate their quality of life (SF-PCS12, SF-MCS12). All patients completed those questionnaires before starting Difelikefalin treatment (t0) and after one month of treatment (t1), 15 of them were evaluated also after three months (t3) and 10 patients, those who first started therapy, reached the assessment at six months (t6). Results Statistical analysis of our preliminary study shows very encouraging data regarding the efficacy of difelikefalin on CKD-aP and sleep quality. As shown in Table 2, we recorded a significant decrease (p value <.001, ƞ2 0.552) in the intensity of itching, most noticeable in the first month, confirming that the effect of this drug is evident and considerable already after four weeks. Our data also demonstrate a significant and lasting positive effect of difelikefalin on sleep quality (p value 0.006, ƞ2 0.592), as shown in Table 3. We found no significant data on the improvement in the QoL of the patients in the study, probably due to the difficulty in standardising this complex feature and due to the limited size of the statistical sample. Furthermore, it should be considered that 3 of the patients enrolled in the study had to discontinue the medication due to the onset of side effects such as diarrhea and headache. Conclusion The most influential limitation of this retrospective observational study is the small number of recruited patients, in addition to the fact that not all of them reached a 6-months treatment evaluation. Our aim is to complete the study by enrolling a larger number of patients from our Dialysis Centre and to monitor the effect of difelikefalin during a longer treatment period, in order to achieve a more accurate analysis and significative results applicable on a larger scale. As far as we can currently evaluate, this drug is significantly effective in reducing CKD-aP and thus in improving the quality of sleep.

Abstract PO3-20-02: Olaparib front line therapy with endocrine therapy in locally advanced unresectable or in metastatic breast cancer: OFELIA TRIAL

Abstract INTRODUCTION: Currently, patients with recurrent or metastatic hormone-sensitive breast cancer are treated with endocrine therapy (ET) in combination with cyclin inhibitors, as it has been shown to improve both overall survival and progression-free survival. However, it has been observed that patients with gBRCA1 or gBRCA2 mutations, who receive treatment with endocrine therapy and CDK4/6 inhibitors, have lower OS and lower PFS compared to those without mutations. These findings could be due to the presence of higher cyclin E mRNA levels, which encode the protein that stimulates CDK2 activity provoking a resistance to CDK4/6 inhibitors. Having this said, the use of PARP inhibitors a potential first-line therapeutic option in combination with endocrine therapy could be an option to be re evaluated. JUSTIFICATION: PARP inhibitors (iPARP) are recommended in international guidelines as second-line palliative treatment and also as adjuvant management in the case of Olaparib. The use of iPARP is approved only as a second-line treatment in HER2 hormone-sensitive breast cancer, according to the results of the EMBRACA and OlympiAD clinical trials. However, these two clinical trials were not designed to evaluate its effectiveness as first-line palliative treatment. Given that patients with gBRCA mutations have lower overall survival when administered cyclin inhibitors (iCDK 4/6) + Endocrine therapy (ET) compared to those without mutations, it is necessary to reevaluate the use of iPARP as first-line palliative treatment in conjunction with ET, with the expectation of achieving a similar objective response rate and progression-free survival. OBJECTIVE: To Determine the ORR in patients with recurrent or metastatic hormone-sensitive HER2-negative breast cancer managed with PARP inhibitors + Endocrine therapy. HYPOTHESIS: The use of PARP inhibitors in combination with endocrine therapy will have an objective response rate of 60% or higher in both early stages and advanced disease. METHODOLOGY: Phase 2 open-label, multicenter clinical trial. Study Population: Cohort : All pre- or postmenopausal patients with a diagnosis of recurrent or metastatic hormone-sensitive HER2-negative breast cancer with gBRCA1 and/or gBRCA2 mutation. Sample: The inclusion of patients will be based on meeting the inclusion criteria. We plan to achieve an ORR of at least 60% with an acceptable minimum of 40%. Assuming a one-sided alpha level of 0.05 and statistical power of 80%, a two-stage Simon design was used to calculate the required sample size. In the first stage, a minimum of 23 patients is assumed, of which 14 patients need to achieve the desired response rate to proceed to the second stage. In the second stage, an additional 28 patients will be added to obtain a total sample size of 51 patients. The objective response rate will be evaluated using RECIST v1.1 criteria at 8 weeks after initiating treatment, with continued assessment during the first year, followed by assessments every 12 weeks during the second and third year, and then every 24 weeks until progression or toxicity. EXPECTED RESULTS: PARP inhibitors + Endocrine therapy will have a similar ORR as reported with cyclin inhibitors + Endocrine therapy, as well as a benefit in progression-free survival. Citation Format: Carlos Arturo González Núñez, Paula Cabrera-Galeana, Juan Enrique Bargalló Rocha, Rafael Vazquez-Romo, Sergio Aguilar-Villanueva, Alexandra Garcilazo, Areli Velazquez-Martinez, Andrea Maliachi, Ruben Rodriguez. Olaparib front line therapy with endocrine therapy in locally advanced unresectable or in metastatic breast cancer: OFELIA TRIAL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-02.

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. Patients self-administered FlecIH over 8minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90minutes using a 12-lead Holter. Mean age was 60.5 years, mean body mass index was 27.0kg/m2, and 34.7% of the patients were women. All patients had≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for≤24 hours. The conversion rate was 42.6% (95%CI: 33.0%-52.6%) with a median time to conversion of 14.6minutes. The conversion rate was 46.9% (95%CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Abstract 3824: Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis

Abstract The combinations of oral fluoropyrimidines and cisplatin such as capecitabine and cisplatin (XP) or 5-FU and cisplatin (FP) are regarded as a standard therapy against HER-2 positive advanced gastric cancer (AGC). Trastuzumab-XP(HXP) and trastuzumab-FP(HFP) is the most common regimen against AGC in Korea. The aim of the present study is to evaluate the effectiveness of trastuzumab-XP vs trastuzumab-FP. Patients with HER2-positive AGC were assigned to the trastuzumabXP or trastuzumabFP group. We then retrospectively compared the efficacy and safety between both groups. As a first-line chemotherapy, trastuzumab in combination with XP or FP was administered to 2,399 patients: 1,913 with HXP and 486 with HFP. In the HXP group vs HFP group, median progression-free survival (mPFS), and median overall survival (mOS) were 8.02 vs 6.08 months (p <0.0001) and 13.27 vs 9.89 months (p <0.0001). In HFP group, mPFS and mOS were 10.15 vs 5.36 months (p <0.0001) and 15.15 vs 8.90 months (p <0.0001) in comparison HFP-H maintenance to HFP group. In HXP group, mPFS and mOS were 10.64 vs 13.44 vs 5.03 months (p <0.0001) and 20.14 vs 22.18 vs 9.10 months (p <0.0001) in comparison HXP-H maintenance, HXP-HX maintenance, and HXP group. Trastuzumab in combination with XP and HX maintenance is a potential first-line therapeutic option for patients with HER2-positive AGC. Citation Format: hyun woo Lee, Jang-Hee Kim, Seok Yun Kang, Tae Jun Park, Yong Won Choi. Efficacy of trastuzumab in combination with capecitabine and cisplatin vs 5-FU and cisplatin therapy for Korean patients with HER2-positive advanced gastric cancer Health Insurance Review and Assessment service (HIRA) data retrospective analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3824.

Trimethoprim-sulfonamide: a valid antimicrobial treatment in foals?

Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are reported on the basis of recent publications in foals. The review intends to share significant information about the common infections that are most likely responsive to TMPS treatment in foals and, as such, where TMPS might be considered a suitable first-line therapeutic option.

Mechanobiology of bacterial biofilms: Implications for orthopedic infection.

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first-line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug-resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone-implant interface.

JANUS KINASE INHIBITORS FOR RELAPSING POLYCHONDRITIS TREATMENT: A HYPOTHESIS

Relapsing polychondritis (RP) is a rare autoimmune disease marked by recurrent episodes of inflammation impacting cartilaginous structures. The underlying mechanism has not been fully elucidated; however, comprehensive genetic and histopathological evaluations have revealed the involvement of specific genes, cell-mediated immunity, and humoral immunity in the pathogenesis of RP. The spectrum of symptoms associated with this condition ranges from mild manifestations to severe, life-threatening presentations. Treatment options vary depending on the disease severity. Non-steroidal anti-inflammatory drugs, colchicine, dapsone, and systemic corticosteroids are commonly utilized as first-line therapeutic options. Furthermore, cyclophosphamide, methotrexate, azathioprine, cyclosporine, and biological disease-modifying anti-rheumatic drugs are employed as second-line treatment. Nevertheless, there is insufficient data regarding the use of Janus kinase inhibitors (JAKi) in RP patients as a treatment option. This hypothesis suggests that JAKi may be a viable treatment option for relieving symptoms in these patients.

An Overview of Adalimumab Therapy for Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease known for causing pain, stiffness, and reduced mobility in the axial skeleton. Adalimumab, a tumor necrosis factor (TNF) inhibitor, has emerged as a promising therapeutic option for AS. This systematic review involved a comprehensive search of randomized controlled trials related to AS treatment, conducted in major databases such as MEDLINE, Google Scholar, and PubMed. The search terms encompassed ankylosing spondylitis, adalimumab, methotrexate, other non-biologic DMARDs, glucocorticoids, NSAIDs, and analgesics. A total of 14 randomized controlled trials with 4,500 participants were included in the review. The review's results revealed that adalimumab demonstrated notable superiority when compared to a placebo. It effectively reduced disease activity, improved physical function, and lowered inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Adalimumab demonstrated a favorable safety profile, with adverse events comparable to those observed with placebo. Based on the results, adalimumab is deemed an effective treatment for AS, showcasing its potential as a first-line therapeutic option. Notably, no significant increase in adverse events was observed compared to placebo. However, the conclusion emphasizes the need for further studies with extended follow-up durations to ascertain the long-term efficacy and safety of adalimumab in AS management. This systematic review provides valuable insights supporting the use of adalimumab in the treatment of AS and underscores the importance of ongoing investigations into its long-term effects to optimize its clinical utilization in AS patients.

Diagnostic and therapeutic role of endoscopic ultrasound in liver diseases: A systematic review and meta-analysis.

In hepatology, the clinical use of endoscopic ultrasound (EUS) has experienced a notable increase in recent times. These applications range from the diagnosis to the treatment of various liver diseases. Therefore, this systematic review summarizes the evidence for the diagnostic and therapeutic roles of EUS in liver diseases. To examine and summarize the current available evidence of the possible roles of the EUS in making a suitable diagnosis in liver diseases as well as the therapeutic accuracy and efficacy. PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were extensively searched until October 2023. The methodological quality of the eligible articles was assessed using the Newcastle-Ottawa scale or Cochrane Risk of Bias tool. In addition, statistical analyses were performed using the Comprehensive Meta-Analysis software. Overall, 45 articles on EUS were included (28 on diagnostic role and 17 on therapeutic role). Pooled analysis demonstrated that EUS diagnostic tests had an accuracy of 92.4% for focal liver lesions (FLL) and 96.6% for parenchymal liver diseases. EUS-guided liver biopsies with either fine needle aspiration or fine needle biopsy had low complication rates when sampling FLL and parenchymal liver diseases (3.1% and 8.7%, respectively). Analysis of data from four studies showed that EUS-guided liver abscess had high clinical (90.7%) and technical success (90.7%) without significant complications. Similarly, EUS-guided interventions for the treatment of gastric varices (GV) have high technical success (98%) and GV obliteration rate (84%) with few complications (15%) and rebleeding events (17%). EUS in liver diseases is a promising technique with the potential to be considered a first-line therapeutic and diagnostic option in selected cases.

Post-ligation cardiac syndrome after surgical versus transcatheter closure of patent ductus arteriosus in low body weight premature infants: a multicenter retrospective cohort study.

Transcatheter patent ductus arteriosus (PDA) closure is a safe and effective alternative to surgical ligation in low-body-weight infants. Post-ligation cardiac syndrome (PLCS) is defined as severe hemodynamic and respiratory collapse within 24h of PDA closure, requiring initiation or an increase of an inotropic agent by > 20% of preligation dosing and an absolute increase of at least 20% in ventilation parameters compared with the preoperative value. Whilst PLCS is routinely observed after surgery, its incidence remains poorly described following transcatheter closure. This study aimed to compare the incidence of PLCS after surgical versus transcatheter closure of PDA in low-body-weight premature infants. Propensity scores were used to compare surgical (N = 78) and transcatheter (N = 76) groups of preterm infants who underwent PDA closure at a procedural weight less than 2000g in two tertiary institutions between 2009 and 2021. The primary outcome was the incidence of PLCS. Secondary outcomes included overall mortality before discharge, risk factors for PLCS, and post-procedural complications. Procedural success was 100% in both groups. After matching, transcatheter group experienced no PLCS vs 15% in the surgical group (p = 0.012). Furthermore, overall mortality (2% vs 17%; p = 0.03) and major complications (2% vs 23%; p = 0.002) were higher in the surgical group. Surgery (100% vs 47%; p < 0.01), gestation age (25 ± 1 vs 26 ± 2weeks, p < 0.05) and inotropic support before closure (90% vs 29%; p < 0.001) were associated with PLCS occurrence. Conclusion: Transcatheter PDA closure may be equally effective but safer than surgical PDA closure in low-body-weight premature infants. What is Known: • Post-ligation cardiac syndrome is a serious and common complication of surgical closure of the ductus arteriosus in preterm infants. • Transcatheter closure of preterm ductus arteriosus is a safe and effective technique that is becoming more and more common worldwide. What is New: • Device closure is safer than surgical ligation for patent ductus arteriosus closure in preterm infants and may be the first-line non-pharmacological therapeutic option in this indication in experienced teams. • Our findings should encourage neonatologists and pediatric cardiologists to start and/or strengthen a durable interventional program for transcatheter PDA closure in premature infants.

Clinical relevance and implementation into daily practice of pharmacist-prescribed medication for the management of minor ailments

Background: Autonomous pharmacist prescribing was legally introduced in Switzerland in 2019 with the reclassification from prescription medication to pharmacist prescribing of 105 medications for sixteen indications. Its aim was to limit medical consultations and healthcare costs.Objectives: To evaluate the clinical relevance of the pharmacy prescribing medications compared to the over-the-counter medications (OTCs) and to evaluate its implementation into daily practice.Methods: A comparison was undertaken by clinical pharmacists to evaluate chemical and galenical equivalences between pharmacy prescribing medications and OTCs using compendium. ch and pharmavista. ch. Then, a scoping review was carried out in October 2021 to determine clinical relevance according to clinical guidelines’ recommendations. Clinical relevance was completed by determining if pharmacy prescribing medications were part of a homogeneous therapeutic class (no differences in efficacy and safety considered in clinical guidelines, but rather inter-molecular differences) that included an OTC medication. To identify the most clinically relevant pharmacy prescribing medications, first-line treatments were considered. The implementation into daily practice in Swiss community pharmacies was evaluated through an online questionnaire distributed via e-mail from the national pharmacists’ association and LinkedIn®. It included 15 questions divided in: pharmacy demographics, experience on pharmacy prescribing, use of prescribing medications and opinion about the them.Results: Of the 105 pharmacy prescribing medications, 20 (19.0%) were first-line treatments without OTC equivalences. Six of them were OTCs reclassified for safety reasons. Ten medications (9.5%) showed a negative clinical relevance (they were not first-line therapeutic options to support pharmacist when managing patients or considered as to be avoided) compared to the OTCs available. For the questionnaire, 283 pharmacists from the German (40.3%), French (37.1%) and Italian-speaking regions (16.9%) answered. In the previous 6 months, 41.7% pharmacies had delivered 10–50 medications and 30.0% between 1 and 10 medications. In situations where patients could be equally treated with a pharmacy prescribing medication or OTC (with an identical OTC, similar OTC or an OTC for the same therapeutic group): 75.6%, 74.9% and 84.8% of pharmacists, respectively, would have chosen OTCs because it required less documentation and it did not require patients’ payment for the service. In addition, pharmacists’ lack of training was also mentioned as barrier for providing the service.Conclusion: Most pharmacist prescribing medications do not present clinical advantages compared to OTCs. In addition, other barriers for implementation were also pharmacists’ training and patient medications costs.

Novel Immunopharmacological Drugs for the Treatment of Allergic Diseases.

The exponential rise in the prevalence of allergic diseases since the mid-twentieth century has led to a genuine public health emergency and has also fostered major progress in research on the underlying mechanisms and potential treatments. The management of allergic diseases benefits from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting players of allergic inflammation at distinct pathophysiological steps. Prominent examples include therapeutic monoclonal antibodies against cytokines, alarmins, and their receptors, as well as small-molecule modifiers of signal transduction mainly mediated by Janus kinases and Bruton's tyrosine kinases. However, the first-line therapeutic options have yet to switch from symptomatic to disease-modifying interventions. Here we present an overview of available drugs in the context of our current understanding of allergy pathophysiology, identify potential therapeutic targets, and conclude by providing a selection of candidate immunopharmacological molecules under investigation for potential future use in allergic diseases.

The Role of the Complement in Clear Cell Renal Carcinoma (ccRCC)—What Future Prospects Are There for Its Use in Clinical Practice?

In recent years, the first-line available therapeutic options for metastatic renal cell carcinoma (mRCC) have radically changed with the introduction into clinical practice of new immune checkpoint inhibitor (ICI)-based combinations. Many efforts are focusing on identifying novel prognostic and predictive markers in this setting. The complement system (CS) plays a central role in promoting the growth and progression of mRCC. In particular, mRCC has been defined as an “aggressive complement tumor”, which encompasses a group of malignancies with poor prognosie and highly expressed complement components. Several preclinical and retrospective studies have demonstrated the negative prognostic role of the complement in mRCC; however, there is little evidence on its possible role as a predictor of the response to ICIs. The purpose of this review is to explore more deeply the physio-pathological role of the complement in the development of RCC and its possible future use in clinical practice as a prognostic and predictive factor.

A 24-Week, Multi-Center, Randomized, Open-Label Clinical Trial Comparing the Effects of Xuezhikang and Atorvastatin on Glucose Metabolism in Patients with Dyslipidemia and Prediabetes (XTREME Study): Design of the Study Protocol

Background: Statins, a first-line therapeutic option for atherosclerotic cardiovascular disease (ASCVD), have prompted concerns regarding dysglycemia and diabetes, thus posing a dilemma in treating patients with prediabetes. Xuezhikang (XZK) decreases blood cholesterol levels without affecting glucose metabolism, and may serve as a potential substitute. Methods: The XTREME study is a prospective, randomized, open-label, multi-center trial evaluating whether XZK 1200 mg/d, compared with atorvastatin 20 mg/d, has favorable effects on HbA1c levels after 24 weeks of treatment in patients with dyslipidemia and prediabetes. After a 1-week run-in period for adherence assessment, the study will randomly assign (1:1) 392 patients meeting the protocol inclusion criteria to one of two treatment groups: an experimental group (XZK 1200 mg/day) or a control group (atorvastatin 20 mg/day). All participants will be recruited from approximately 20 Chinese medical centers. The last participant is planned to be recruited before December 2023. The primary endpoint will be change in HbA1c level from baseline to 24 weeks, or before anti-diabetic therapy initiation within 24 weeks. The key secondary outcomes will include other biomarkers reflecting blood glucose or lipid metabolism. Discussion: Delaying diabetes is desirable for individuals with prediabetes. The XTREME trial presents a unique opportunity to demonstrate whether XZK might provide an alternative to statins for patients with dyslipidemia and prediabetes.

Multicentre Study Into the Use of Polyethylene Glycol With Electrolytes Over at Least 6 Months to Treat Constipation in Paediatric Populations.

Constipation is a common clinical problem in children, for which the first-line therapeutic options are osmotic laxatives, mainly polyethylene glycol (PEG). These treatments are often prescribed for short or limited periods, with progressive treatment withdrawal often resulting in relapses. However, there are a few studies into the long-term use (≥6 months) of PEG 3350 with electrolytes (PEG+E) in terms of the patients' clinical evolution. To assess bowel movement and other relevant symptoms in children with constipation receiving PEG+E (≥6 months), as well as parent/caregiver satisfaction with this treatment. A retrospective, observational, descriptive, longitudinal, and multicentre study was carried out on 74 children diagnosed with functional constipation (ROME IV criteria) who had received PEG+E (≥6 months). Bowel control was assessed using the Bristol stool scale, and the parent's/caregiver's perception of the treatment was also evaluated employing a nonvalidated questionnaire. Children with an average duration of constipation >1 year experienced a significant improvement in bowel movements and stool consistency when using PEG+E. The mean duration of use was 18.6 (±13.4) months, without the need to adjust the dose for weight. All clinical symptoms improved significantly except bloating, and all the parents/caregivers confirmed these clinical improvements. Children treated with PEG+E (≥6 months) normalised their bowel movements, improving the clinical symptoms related to constipation in the absence of serious advert events or the need for dosage adjustments due to weight gain. Parents/caregivers reported good satisfaction with PEG+E treatment.

Parenteral Vancomycin in the Treatment of MRSA-Associated Diabetic Foot Infections: An Unnecessary Risk.

Diabetic foot infections (DFIs) are a common and costly complication of diabetes. Soft tissue and bone infections in DFIs frequently lead to amputation and/or sepsis which can be costly for both the patient and the healthcare system. Staphylococcus aureus is the most commonly identified causative agent in DFIs, and people with diabetes may have an increased risk of infection with methicillin-resistant Staphylococcus aureus (MRSA). In addition to increased susceptibility to severe infection, MRSA in DFIs is associated with high rates of treatment failure, morbidity, and hospitalization costs meaning appropriate treatment is a high priority. While hospitalized patients are usually treated with intravenous (IV) vancomycin, this can be costly in terms of inpatient stays, staffing costs, and adverse events. For example, vancomycin-associated acute kidney injury not only delays hospital discharge and increases costs but is also a particular concern for patients with diabetes who already have an increased risk of kidney problems. Vancomycin-resistant strains of S. aureus have also been identified, which means that alternative treatment options may need to be explored. Treatment alternatives to IV vancomycin, including oral antibiotics, have been shown to provide similar efficacy, with reduced costs, outpatient or home-based administration, and with fewer serious adverse effects. Although infectious disease specialists often use IV vancomycin alone, or in combination, as a first-line therapeutic option, they are increasingly seeing the value of outpatient or at-home oral antibiotics as an alternative. This manuscript reviews the evidence for true costs of vancomycin therapy for MRSA-associated DFIs and examines the alternatives.

Clinical characteristics and management outcomes in isolated nail lichen planus: A retrospective case series.

Background Isolated nail lichen planus (NLP) without mucocutaneous involvement is rare. Literature about the clinical profile and management is scarce. Aims/Objective We attempted to characterize the clinico-demographic profile and analyze the management outcome of patients with isolated nail lichen planus. Methods Records of 15 patients were evaluated, and their demographic profile, clinical features of the nail matrix and nail bed disease, onychoscopy findings, histopathological features, treatment given, and follow-up progress were analysed. Results Data from 15 patients were collected. The mean age of the patients was 28.6 ± 19.0 years (range 3.5 years to 56 years). The gender ratio was 0.8 with 7 males and 8 females. The average disease duration at presentation was 2.8 ± 2.6 years (6 months-9 years). The average number of nails involved was 16.4 ± 4.6 (8-20 nails). All 20 nails were involved in 9 (60%) patients. Nail matrix -involvement was seen in all, with onychorrhexis being the most common manifestation, which was seen in 11 (73.3%) patients. Nail bed involvement was seen in 11 (73.3%) patients, with onycholysis being the most common presentation. Severe nail disease was seen in 7 (46.7%) patients, and 5 (33.3%) had pterygium involving an average of 3.4 nails. Moderate to good improvement was observed in 9 (60%) patients after an average of 6.1 ± 2.4 (3-9) treatment sessions with intramuscular and intramatricial triamcinolone acetonide injection. Of these, 2/9 (22.2%) developed disease recurrence in a few nails after an interval of 1 and 1.5 years, respectively. Two patients achieved complete clinical cures that persisted beyond 2 years of follow-up. Limitations Retrospective nature of the series and the small sample size are the major limitations. Conclusion The risk of permanent disfigurement is high in NLP and calls for an early diagnosis and prompt treatment. Intralesional and intramuscular steroids are first-line therapeutic options depending upon the number of nails involved.

Do High Ventilation Mode Affect the Success Rates of Retrograde Intrarenal Surgery? A Single-Blind Randomized, Prospective, Single-Center Study.

Purpose: Retrograde intrarenal surgery (RIRS) has been accepted as a first-line therapeutic option for kidney stones <2 cm. Renal mobility might be a challenging situation for the surgeon targeting the laser, thereby limiting the renal mobility during surgery might affect the surgical success. The main objective of the present trial was to evaluate the effect of two different ventilation modes on the efficacy and safety of RIRS performed under general anesthesia. Materials and Methods: The patients undergoing RIRS from January 2023 to April 2023 were prospectively enrolled in the trial. In the standard ventilation (SV) mode, the tidal volume was 8 to 10 mL/kg with respirations per minute being 10-15, whereas in the high ventilation (HV) mode the tidal volume was reduced to 6 to 8 mL/kg with the frequency being increased to 15 to 18 respirations/minute. For the purposes of the trial and the randomization, the anesthesiologist was informed about the ventilation mode used, whereas the surgeon was blinded. The surgical success rates and the observed complications were compared between SV and HV modes. Results: A total of 144 patients were enrolled with the mean age 48.78 ± 14.16 years. The mean duration of operation was 62.9 ± 26.3 minutes in the SV group, whereas it was 58.4 ± 20.1 minutes in the HV group (p = 0.031). Fragmentation rate of the stones per minute was higher in the HV group with the difference being statistically significant (p = 0.003). In the preoperative period, while hematuria was seen at higher rates in the HV group, the difference was not statistically significant (p = 0.671). Stone-free rates (Grades A-B-C) and the rates of postoperative complications were comparable between the groups (p = 0.605 and p = 0.676, respectively). Conclusion: Using HV mode during the RIRS decreased the operative time and provided the surgeon with the ability to target the laser more effectively. Surgeons might prefer using the HV mode during RIRS in a mobile kidney to reduce their operative time and perform comfortable surgery. ClinicalTrials.gov: The trial is registered at ClinicalTrials.gov with the registration number of NCT05792670.

Clinical outcome of surgical management of mild cervical compressive myelopathy based on minimum clinically important difference

BACKGROUND CONTEXTCervical compressive myelopathy (CCM), caused by cervical spondylosis (cervical spondylotic myelopathy [CSM]) or ossification of the posterior longitudinal ligament (OPLL), is a common neurological disorder in the elderly. For moderate/severe CCM, surgical management has been the first-line therapeutic option. Recently, surgical management is also recommended for mild CCM, and a few studies have reported the surgical outcome for this clinical population. Nonetheless, the present knowledge is insufficient to determine the specific surgical outcome of mild CCM. PURPOSETo examine the surgical outcomes of mild CCM while considering the minimum clinically important difference (MCID). STUDY DESIGNRetrospective study. PATIENT SAMPLEPatients who underwent subaxial cervical surgery for CCM caused by CSM and OPLL between 2013 and 2022 were enrolled. OUTCOME MEASURESThe Japanese Orthopedic Association score (JOA score) was employed as the clinical outcomes. Based on previous reports, the JOA score threshold to determine mild myelopathic symptoms was set at ≥14.5 points, and the MCID of the JOA score for mild CCM was set at 1 point. METHODSThe patients with a JOA score of ≥14.5 points at baseline were stratified into the mild CCM and were examined while considering the MCID. The mild CCM cohort was dichotomized into the improvement group, including the patients with an achieved MCID (JOA score ≥1 point) or with a JOA score of 17 points (full mark) at 1 year postoperatively, and the nonimprovement group, including the others. Demographics, symptomatology, radiographic findings, and surgical procedure were compared between the two groups and studied using the receiver operating characteristic (ROC) curve. RESULTSOf 335 patients with CCM, 43 were stratified into the mild CCM cohort (mean age, 58.5 years; 62.8% male). Among them, 25 (58.1 %) patients were assigned to the improvement group and 18 (41.9 %) were assigned to the nonimprovement group. The improvement group was significantly younger than the nonimprovement group; however, other variables did not significantly differ. ROC curve analysis showed that the optimal cutoff point of the patient's age to discriminate between the improvement and nonimprovement groups was 58 years with an area under the curve of 0.702 (p=.015). CONCLUSIONSIn the present study, the majority of patients with mild CCM experienced improvement reaching the MCID of JOA score at 1 year postoperatively. The present study suggests that for younger patients with mild CCM, especially those aged below 58 years, subjective neurological recovery is more likely to be obtained. Meanwhile, the surgery takes on a more prophylactic significance to halt disease progression for older patients. The results of this study can help in the decision-making process for this clinical population.

Enhancing prognostic accuracy in head and neck squamous cell carcinoma chemotherapy via a lipid metabolism-related clustered polygenic model

ObjectiveSystemic chemotherapy is the first-line therapeutic option for head and neck squamous cell carcinoma (HNSCC), but it often fails. This study aimed to develop an effective prognostic model for evaluating the therapeutic effects of systemic chemotherapy.MethodsThis study utilized CRISPR/cas9 whole gene loss-of-function library screening and data from The Cancer Genome Atlas (TCGA) HNSCC patients who have undergone systemic therapy to examine differentially expressed genes (DEGs). A lipid metabolism-related clustered polygenic model called the lipid metabolism related score (LMRS) model was established based on the identified functionally enriched DEGs. The prediction efficiency of the model for survival outcome, chemotherapy, and immunotherapy response was evaluated using HNSCC datasets, the GEO database and clinical samples.ResultsScreening results from the study demonstrated that genes those were differentially expressed were highly associated with lipid metabolism-related pathways, and patients receiving systemic therapy had significantly different prognoses based on lipid metabolism gene characteristics. The LMRS model, consisting of eight lipid metabolism-related genes, outperformed each lipid metabolism gene-based model in predicting outcome and drug response. Further validation of the LMRS model in HNSCCs confirmed its prognostic value.ConclusionIn conclusion, the LMRS polygenic prognostic model is helpful to assess outcome and drug response for HNSCCs and could assist in the timely selection of the appropriate treatment for HNSCC patients. This study provides important insights for improving systemic chemotherapy and enhancing patient outcomes.