Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study.

BACKGROUND: New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. METHODS: This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. RESULTS: Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point's reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. CONCLUSION: rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. TRIAL REGISTRATION: CTRI/2023/05/053247.

Evaluation of short-term face rejuvenation effects of non-ablative bipolar radiofrequency treatment performed by Med-RF© device.

OBJECTIVE: Skin laxity and wrinkling are common signs of the aging process. This physiological condition of the skin is often accompanied by psychological and social concerns, especially for females, entailing considerable expenses for cosmetics and pharmaceuticals to cease or slow down its advancement. The objective of this study was to evaluate the short-term impact of a new non-ablative radiofrequency device available in the skin face cosmetic field. METHODS: A randomized study was run on 62 healthy subjects with normal-age related-grade skin laxity, subdivided into two groups. Group 1 received one treatment with Modula RF device (Wavemed, San Cesareo RM, Italy) over the whole face surface. Group 2 received three monthly treatments. RESULTS: Clinical improvements of the exposed areas were detected by measuring skin parameters, such as total water content, elasticity, and sebum levels at baseline and 1 h after the treatment. Data showed significant effects of Med-RF treatment on skin hydration (p < 0.001), skin elasticity (p < 0.0001), and sebum (p = 0.0009). Moreover, a negative linear correlation was obtained between women's age and hydration. CONCLUSION: In conclusion, the results of this study suggest that radiofrequency significantly improves the subjective and objective judgment of patients and doctors, supported by the positive results obtained on the skin quality parameters evaluated. These results confirm that Med-RF technology represents an important tool to achieve face rejuvenation in the field of non-invasive procedures.

Design, development and validation of a questionnaire to assess dentists' knowledge and experience in diagnosing, recording, and managing root caries.

OBJECTIVES: The prevalence of root caries is increasing globally, especially in the elderly population, and even though the number of patients with root caries lesions is augmenting, there are still many discrepancies in how dentists manage this condition. The present study aimed to develop and validate a questionnaire to evaluate how dentists diagnose, record and manage root caries lesions, and to verify the validity and reliability of this questionnaire. MATERIALS AND METHODS: An expert panel developed a self-administered questionnaire survey with three domains: (1) dentists' knowledge on diagnosis, recording, and managing root caries; (2) information about their current general clinical routines; (3) their demographics. The original English [E] version was translated into three different languages (French [F], German [G], Italian [I]), and subsequently back-translated into English by independent dentists. For the validation, 82 dentists (20-22 for each of the translated versions) accepted to answer the questionnaire at two different time-points (with 1-week interval). The data was quality checked. Construct validity, internal reliability, and intra-class correlation (ICC) were assessed. RESULTS: Seventy-seven dentists completed the questionnaire twice [E: 17; F: 19; G: 19; I: 22]. The mean ICC (standard deviation) was 0.98(0.03) for E, 0.90(0.12) for F, 0.98 (0.04) for G, and 0.98 (0.01) for I. Overall, the test-retest reliability was excellent (mean ICC (SD): 0.96 (0.08)). Furthermore, the questionnaire demonstrated good internal reliability (inter-observer reliability; Fleiss kappa: overall:0.27(fair); E:0.30 (fair); F: 0.33(fair); G: 0.33(fair); I: 0.89 (almost perfect)). CONCLUSION: The questionnaire was validated and is suitable to be used in the four languages to assess the knowledge of dentists on diagnosing, recording and managing root caries. CLINICAL SIGNIFICANCE: The present questionnaire was validated and seems to be a good tool to evaluate how dentists diagnose, record, and manage root caries lesions both in its original (English) and its translated (French, German, and Italian) versions.

LAight® Therapy Significantly Enhances Treatment Efficacy of 16 Weeks of Topical Clindamycin Solution in Hurley I and II Hidradenitis Suppurativa: Results from Period A of RELIEVE, a Multicenter Randomized, Controlled Trial.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, burdensome skin disease where medical first-line treatment is still limited to long-term, topical and/or systemic antibiotics. The RELIEVE study aimed at evaluating the efficacy of LAight® therapy - a combination of intense pulsed light and radiofrequency - as an adjunct treatment to first-line therapies in Hurley stage I and II HS. METHODS: The RELIEVE study was performed as a two-period multicenter randomized controlled trial with blinded assessment. For period A from week 0 to week 16, the 88 participating subjects were randomized into either an intervention group (IG) or a control group (CG). The IG received topical clindamycin 1% solution combined with 8 additional bi-weekly treatments with LAight® therapy. The CG was treated with topical clindamycin 1% solution only. After 16 weeks, patients entered open-label period B and both groups were treated exclusively with LAight® therapy for an additional 16 weeks (8 sessions). The primary efficacy endpoint was the change in International Hidradenitis Suppurativa Score System (∆IHS4) at week 16 to baseline. Secondary endpoints were DLQI, HiSCR, Pain-NRS, and HADS. RESULTS: In total, from the 88 patients enrolled in RELIEVE, 81 patients were included in the endpoint analysis after period A. After 16 weeks of treatment, the ∆IHS4 of the group treated with the combination of LAight® therapy and topical clindamycin 1% solution was -7.2 ± 6.7 (-60.0%), which was significantly higher in magnitude than the ∆IHS4 in the group treated with clindamycin 1% solution alone (-1.8 ± 5.6, -17.8%, p < 0.001). Secondary endpoints, including other clinical scores as well as patient-reported outcomes, confirmed that the efficacy of the combined treatment was superior to monotherapy. CONCLUSION: The results of the primary endpoint analysis of period A of the RELIEVE study show that the combined therapy with LAight® and topical clindamycin 1% solution, resulted in a significantly higher decrease in disease severity and an improvement of quality of life in comparison to topical clindamycin 1% solution monotherapy. Treatment was well tolerated, and side effects were all mild and transitory. These data speak for the implementation of the combined treatment as a first-line therapy in Hurley stage I and II HS. LAight® therapy as long-term monotherapy (results from period B), will be analyzed in a consecutive paper.

How do carious root lesions develop after the end of professional preventive measures?-Preliminary findings of a randomized clinical trial.

Aim of this randomized clinical trial was to assess the development of root caries lesions with and without (adjuvant) professional prevention treatment over 24 months. 20 participants with two or three non-cavitated root carious lesions were included (n = 52), whereby lesions were randomly assigned to one out of three groups depending on varnish application (CF: Cervitec F [n = 20], P: placebo [n = 20], DP: Duraphate [n = 12]). All lesions were assessed by quantitative light-induced fluorescence (QLF; QRayCam); following outcome parameters were analyzed: fluorescence loss (ΔF %), lesion volume (ΔQ %µm2) and bacterial activity (ΔR %). Professional tooth cleaning and adjuvant varnish application were performed at baseline, after 3, 6, and 9 months. A follow-up examination was performed 1 year after preventive care with varnish application 24 months after baseline. ∆F showed a significant time effect in CF (p = 0.03), which was not confirmed in post hoc analysis (p > 0.05). For P and DP, no time effect was detected (p > 0.05). ∆Q was significantly higher 12 months after baseline in CF (p = 0.02). In P, a significant time effect occurred (p = 0.01), without significant results in post hoc testing. ∆R showed higher values at baseline vs. 12 months in CF (p = 0.03) and 24 months compared to 12 months in DP (p = 0.02). Professional preventive treatment inhibited the progression of root caries lesions beyond their termination for 12 months, irrespective of an adjunctive varnish application. Preventive measures have a long-term effect on root carious lesions, even 1 year after their termination.

Does physiotherapy applied in conjunction with compression brace treatment in patients with pectus carinatum have efficacy? A preliminary randomized-controlled study.

PURPOSE: Non-invasive treatment of pectus carinatum (PC) deformity includes the use of a compression brace and exercises. In this study, we aimed to examine the effect of a physiotherapy protocol applied as adjunct to compression brace treatment in patients with PC. METHODS: The study included 30 male patients between 11 and 18 years of age. Patients were randomly assigned into two groups: a brace treatment only group (Group 1) and a brace and physiotherapy group (Group 2). Patient demographics and disease-related properties, protrusion measurements, postural evaluations, deformity perceptions, life quality, and treatment satisfaction were evaluated. RESULTS: Although both groups showed improvements based on external chest measurements related to PC protrusion following treatment (p < 0.001), Group 2 had more benefit from the treatment (effect size > 0.36) and displayed greater improvement in maximum protrusion degree and lateral length values (p < 0.05). Additionally, we found that patient perception of deformity, posture, psychological life quality, and treatment satisfaction scores were significantly better in Group 2 (p < 0.05). CONCLUSION: Owing to the satisfaction and additional benefits observed in the physiotherapy group, we think that a proper cardiopulmonary and musculoskeletal exercise program should be applied concurrently with brace treatment for patients with PC deformity. Nevertheless, long-term outcomes need to be clarified in future studies.

Positional treatment without mechanical ventilation in a very preterm infant with unilateral pulmonary interstitial emphysema: case report and review of the literature.

BACKGROUND: Pulmonary interstitial emphysema (PIE) in very low birth weight infants is a rare but severe complication. Although most of these air leaks develop in mechanically ventilated infants, they have also been reported in infants exposed only to nasal continuous positive airway pressure (CPAP). The optimal treatment for PIE is still under discussion and includes different approaches such as unilateral intubation, high frequency oscillation ventilation and even surgical lobectomy. However, as yet, there has been no report on complete resolution of unilateral PIE by positioning therapy without mechanical ventilation. CASE PRESENTATION: We report the case of a 28+1gestational week twin, 990 g birth weight, Apgar 9-10-10. After stabilization with nasal CPAP the baby received surfactant by less invasive surfactant application (LISA) technique in the delivery room after 35 min of life, and continued respiratory support with nasal CPAP. At day 5 X-ray presented unilateral PIE, while pCO2 increased from 40 mmHg to 55 mmHg and FiO2 from 0.21 to 0.28 to achieve SpO2 in the target range of 89-94%. The baby was treated by strict positioning on the affected hemithorax in a special splint while spontaneously breathing on High Flow Nasal Cannula (HFNC). Complete resolution of the unilateral PIE was observed after 96 h. No chronic lung disease developed. CONCLUSION: For unilateral PIE in very preterm infants, positioning on the affected hemithorax without mechanical ventilation is a therapeutic option.

A novel topical agent in the treatment of seborrheic keratoses: A proof of concept study by clinical and dermoscopic evaluation.

In this proof of concept study, 50 lesions from 15 patients with multiple seborrheic keratoses (SKs) were treated with a novel aqueous solution containing nitric acid, zinc and copper salts, and organic acids (acetic, lactic, and oxalic acid). Treatment consisted in the application of an amount of the solution sufficient to obtain a whitening/yellowish reaction. Application of the nitric-zinc solution was performed every other week until clinical and dermoscopic clearance or crust formation, for a maximum of 4 applications. Efficacy evaluation was performed at 8 weeks (T1) and 6 months (T2). All subjects, who reported no or minimal discomfort during and after the application of the solution, completed the study. At T1, a complete clinical and dermoscopic resolution was observed in 37 lesions after an average of 3 applications/lesion (range 2-4). A partial response, with minimal persistent residual spots, was detected in the remaining 13 lesions. All patients with complete clearance showed no relapses at a 6-month follow-up (T2). The positive preliminary results indicate that this novel solution may represent a promising alternative option for SKs especially in patients not keen or eligible to undergo invasive tissue-destructive procedures.

Satisfaction with dental care among patients who receive invasive or non-invasive treatment for non-cavitated early dental caries: findings from one region of the National Dental PBRN.

BACKGROUND: The objectives were to: (1) quantify patient satisfaction with treatment for early dental caries overall, and according to whether or not (2a) the patient received invasive treatment; (2b) was high-risk for dental caries, and had dental insurance; and (3) encourage practitioners to begin using non-invasive approaches to early caries management. METHODS: Ten practitioners recorded patient, lesion, and treatment information about non-cavitated early caries lesions. Information on 276 consecutive patients with complete data was included, who received either non-invasive (no dental restoration) or invasive (dental restoration) treatment. Patients completed a patient satisfaction questionnaire and were classified as dissatisfied if they did not "agree" or "strongly agree" with any of 14 satisfaction items. RESULTS: Patients had a mean (± SD) age of 41.8 (±15.8) years, 64% were female and 88% were white. Twenty-five percent (n = 68) were dissatisfied in at least one of the 14 satisfaction items. Satisfaction levels did not significantly vary by patient's gender, race, caries risk category, or affected tooth surface location. Overall, 11% (28 of 276) received invasive treatment; satisfaction did not differ between patients who had invasive or non-invasive treatment. Seven patients received invasive treatment at their request even though that was not what their practitioner recommended; 5 out of 6 were satisfied with their treatment nonetheless. CONCLUSIONS: About one-fourth of patients treated for non-cavitated early caries were dissatisfied with at least some aspect of their dental care experience. Satisfaction of patients who received invasive treatment did not differ from those who received non-invasive treatment.

Survival analysis of high-intensity focused ultrasound therapy vs. transarterial chemoembolization for unresectable hepatocellular carcinomas.

BACKGROUND & AIMS: High-intensity focused ultrasound (HIFU) ablation is a non-invasive treatment for unresectable hepatocellular carcinomas (HCCs), but long-term survival analysis is lacking. This study was to analyse its outcome compared to that of transarterial chemoembolization (TACE). METHODS: From October 2003 to September 2010, 113 patients received HIFU ablation as a treatment of HCCs at our hospital. Twenty-six patients had HCCs sized 3-8 cm. Fifty-two patients with matched tumour characteristics having TACE as primary treatment were selected for comparison. Short-term outcome and long-term survival were analysed. RESULTS: In the HIFU group (n = 26), 46 tumours were ablated. The median age of the patients was 69 (49-84) years. The median tumour size was 4.2 (3-8) cm. In the TACE group (n = 52), the median age of the patients was 67 (44-84) years. The median tumour size was 4.8 (3-8) cm. There was no hospital mortality in any of the groups. In the HIFU group, the rates of complete tumour response, partial tumour response, stable disease and progressive disease were 50%, 7.7%, 25.6% and 7.7% respectively, according to the modified Response Evaluation Criteria in Solid Tumours. The TACE group had the corresponding rates at 0%, 21.2%, 63.5% and 15.4% respectively (P < 0.0001). The 1-year, 3-year and 5-year survival rates were 84.6%, 49.2% and 32.3% respectively, in the HIFU group and 69.2%, 29.8% and 2.3% respectively, in the TACE group (P = 0.001). CONCLUSION: HIFU ablation is a safe and effective method for unresectable HCCs. A survival benefit is observed over sole TACE.

Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy.

PURPOSE: To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome. METHODS: The study subjects were 20 patients with biopsy-verified BCC (9) or AK (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod treatment and after 3 months. Lesions were identified clinically and with OCT. Thickness and morphology of the lesions were recorded at each visit. Any remaining lesions were biopsied at follow-up. RESULTS: Complete data sets were available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant patients were excluded. OCT identified all lesions. Previously suggested OCT-criteria identified 5/8 BCCs. Crusting, ulceration and active treatment significantly reduced image quality. All BCCs cleared, but at follow-up residual structures were seen clinically in 4 cases. OCT and histology both ruled out residual BCC. For AKs significant thinning occurred after 1 week of treatment (P = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of all lesions (P = 0.02). CONCLUSIONS: OCT could identify superficial BCC and AK before treatment. Monitoring during imiquimod treatment revealed impaired image quality most likely caused by inflammation, crusting and ulceration. On follow-up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs cleared, but where residual tissue was suspected clinically this could be ruled out by OCT.

Diagnosing and recording root caries: A survey among Swiss dentists.

OBJECTIVES: Despite the increase in the root caries prevalence, little is still known about how dentists manage this condition. The present study aimed to evaluate the knowledge of dentists on diagnosing and recording root caries lesions (RCL). METHODS: The survey consisted of three domains: (1) dentists' knowledge on diagnosing, recording and managing RCL; (2) information about their current general clinical routines; and (3) their demographics. The four Swiss Universities distributed the survey via e-mail lists for alumni or professionals participating in continuing education. The data was quality checked. Construct validity, internal reliability and intraclass correlation (ICC) were assessed. RESULTS: The survey was answered by 383 dentists from 25(out of 26) cantons [mean(SD) working experience: 22.5(12) years]. The majority replied that they see less than 5 patients with RCL per week, whereas 41 have at least 5 per week, and 40 % (157 dentists) do not distinguish RCL from coronal caries in their patients' medical records. When diagnosing active RCL, tactile sensation was the most predominant criterion (n = 380), whereas color (n = 224) and visual appearance (n = 129) of the lesion were less often selected. The most often chosen risk factors for RCL were poor oral hygiene and presence of biofilm.The responses were significantly influenced by the participants' place of education, their age and working area. CONCLUSION: The present survey highlights the huge diversity in diagnosing, recording and assessing risk factors of RCL. The benefits of an appropriate diagnosis, recording and management of risk factors of RCL should be highlighted in under- and postgraduate dental education. CLINICAL SIGNIFICANCE: A great diversity in diagnosing, recording and assessing risk factors of RCL was observed, which migh strongly impact how dentists manage RCL. The study emphasizes the necessity for intensive efforts to bridge the gap between guideline recommendations and their implementation in private dental practices.

Current trends in non-surgical management of Peyronie's disease-A narrative review.

Peyronie's disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non-surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non-surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha-2b can also be an option in such patients. Among other non-invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non-surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non-surgical management of PD is highly warranted.

Effectiveness of Tai Chi as a non-invasive intervention for mild cognitive impairment in the elderly: A comprehensive review and meta-analysis.

The aging population warrants the increase of mild cognitive impairment (MCI) prevalence, a condition that could progress to dementia. Efforts have been made to improve the MCI and prevent its progression, including the introduction of Tai Chi, a Chinese traditional exercise. The aim of this systematic review and meta-analysis was to evaluate the efficacy of Tai Chi in attenuating MCI among the elderly population. Records investigating the effect of Tai Chi exercise intervention on cognitive function among elderly patients were searched systematically from PubMed, ScienceDirect, Google Scholar, and Europe PMC as of April 13, 2023. The risk of bias (RoB 2.0) quality assessment was employed in the quality appraisal of the studies included. Review Manager 5.4.1 was used for data extraction and meta-analysis, where the standard mean difference (SMD) and 95% confidence interval (95%CI) were computed. Eight randomized control trials with a total of 1379 participants were included in this meta-analysis. Six trials assessed Montreal Cognitive Assessment scores, where its pooled analysis suggested that Tai Chi was as effective as conventional exercise (SMD=0.15, 95%CI: -0.11 to 0.40, p=0.26). However, pooled analysis of the Mini-Mental Status Examination suggested that Tai Chi intervention more effectively improved cognitive function and reduced the rate of cognitive impairment in elderly patients (SMD=0.36, 95%CI: 0.18 to 0.54, p<0.01) as compared to the control group. This systematic review and meta-analysis suggest that, in some extent, Tai Chi is efficacious in improving cognitive function and slowing down the rate of cognitive impairment among elderly patients.

Effectiveness of TENS and Acetaminophen for Pain Control During Orthodontic Treatment: A Comparative Study.

Background: Orthodontic treatment often induces pain, especially post appliance placement. This study compares transcutaneous electrical nerve stimulation (TENS) and acetaminophen for orthodontic pain management. Materials and Methods: A randomized trial included 120 fixed orthodontic patients divided into three groups (n = 40): Group A received TENS, group B received acetaminophen, and group C was the control. Data were expressed as mean ± SD. Repeated ANOVA analysis compared mean values, followed by post-hoc Tukey analysis. Pain levels were assessed using a visual analog scale before any intervention and at 30 minutes, 6 hours, and 24 hours post activation. Results: TENS and acetaminophen significantly reduced pain compared to the control. Group A (TENS) showed significant pain reduction post activation. Group B (acetaminophen) exhibited comparable pain relief, with no significant difference between groups. Conclusion: Both TENS and acetaminophen effectively manage orthodontic appliance activation pain.

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression.

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air-liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

Bridging present and future: A narrative review and visionary outlook on innovative solutions for the diagnosis and treatment of urinary incontinence.

Urinary incontinence, characterized by the involuntary leakage of urine, significantly impacts millions globally, affecting their quality of life, social interactions, and psychological well-being. Traditional diagnostic methods and treatments often fall short, especially for refractory urinary incontinence, due to their invasive nature and limited scope for continuous, real-time assessment. This narrative review critically examines current approaches to diagnosing and managing urinary incontinence, highlights significant gaps in practice, and underscores the urgent need for innovative solutions. We explore the evolution of diagnostic and treatment modalities and introduce a preliminary method involving a conceptual catheter device that promises to shift toward non-invasive, real-time monitoring and management. This review synthesizes prevailing research and provides a visionary outlook on how emerging technologies could revolutionize urinary incontinence care, offering a future of personalized, patient-centered strategies. Our discussion extends to the limitations of conventional urodynamic studies, which are often uncomfortable and fail to capture the dynamic nature of urinary incontinence in everyday settings. The proposed preliminary method features an advanced, smart-device solution integrating sensors and artificial intelligence to offer precise, real-time insights into bladder activity. This device, still in the conceptual stages, has the potential to transform the landscape of urinary incontinence management by enhancing diagnostic accuracy and therapeutic efficacy. By bridging the gap between current limitations and future possibilities, this paper aims to inspire ongoing innovation and research in the field of urogynecology.

Study Protocol of a Randomized, Two-Arm, Phase I/II Trial Investigating the Feasibility, Safety, and Efficacy of Local Treatment with US-Guided High-Intensity Focused Ultrasound in Combination with Palliative Chemotherapy in Inoperable Pancreatic Cancer.

BACKGROUND: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects. STUDY DESIGN: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Treatment of Post-Tonsillectomy Hemorrhage With Nebulized Tranexamic Acid: Initial Investigation of a Novel Therapeutic Modality.

OBJECTIVES: The use of nebulized tranexamic acid (TXA) in massive pulmonary hemorrhage is well-described. Published utilization in post-tonsillectomy bleeding (PTB) is limited to a single case. This study examines whether TXA resulted in change of operative intervention necessity and narcotic utilization. METHODS: This was a retrospective cohort study at a single, urban academic medical center in the United States. Chart review was conducted of all patients who presented to the hospital for post-tonsillectomy bleed (PTB) between 3/1/2018 and 7/1/2020. Demographic data, intervention modality, need for control under general anesthesia, and opioid use were collected and analyzed. RESULTS: Twenty-one patients underwent a total of 23 visits for PTB over the study period. Control of hemorrhage without need for operating room intervention for PTB was 100% (6/6) for patients receiving TXA nebulizer and 53% (9/17) for those receiving other treatment modalities. Opioid usage in hospital and on discharge was also lower in patients receiving TXA nebulizers. All results were statistically significant. CONCLUSIONS: Our study supports nebulized TXA as an effective, non-invasive mode of hemostasis in patients presenting to the emergency department for post-tonsillectomy hemorrhage. Nebulized TXA may prevent the need for general anesthesia and operative intervention. Otolaryngologists should consider addition of this novel treatment appropriation of TXA to their management options for postoperative tonsillar hemorrhage.