Success Rate Of Therapy Research Articles

Abstract 4843: Characterization of T-cell metabolic defects in chronic lymphocytic leukemia preclinical model

Abstract Chronic lymphocytic leukemia (CLL) is the most predominant leukemia affecting elderly population in western countries. T-cell dysfunction is a CLL hallmark contributing to the low success rates of adoptive cell therapy in patients. Generally, exhausted states of tumor infiltrating lymphocytes are associated with defects in metabolic and mitochondrial adaptation, preventing normal cytotoxic functions. A handful of recent reports have demonstrated metabolic defects in CLL patients’ T-cells. Nevertheless, the field is still lacking sufficient studies to validate these metabolic changes in the preclinical Eµ-TCL1 murine model which is the most established model for CLL. Our aim is to uncover T-cell mitochondrial and metabolic defects in the Eµ-TCL1 splenic microenvironment. In this study, CLL was induced in mice via the adoptive transfer of leukemic splenocytes from transgenic Eµ-TCL1 mice into wild type (WT) recipients. Multiparameter flow cytometry was used to investigate mitochondrial properties and cellular glucose uptake of splenic CLL CD8+ T-cells. Moreover, we measured the expression levels of PGC-1α, a master regulator of mitochondrial function, and exhaustion-related markers in CD8+ T-cells. T-cell mitochondrial function was measured using mitochondrial stress test following in vitro CD3/CD28 stimulation for 72 hours. Nanostring gene expression analysis was done to compare metabolic gene expression profiles of CD8+ T-cells from either WT or Eµ-TCL1 mice. Probing Eµ-TCL1 splenocytes with mitotracker green and tetramethylrhodamine methyl ester revealed accumulation of depolarized mitochondria in CD8+ T-cells compared to WT counterparts. Our results also showed significant changes in mitochondrial and cellular reactive oxygen species levels as indicated by mitosox and H2DCFDA staining, respectively. Additionally, marked reduction of glucose uptake by Eµ-TCL1 CD8+ T-cells was noted following incubation with 2-NBDG glucose analog. Observed mitochondrial abnormalities in the Eµ-TCL1 CD8+ T-cells were associated with a significant downregulation of PGC-1α expression. Flow cytometry analysis demonstrated a significant increase in the expression of exhaustion markers in Eµ-TCL1 CD8+ T-cells and reduction in self-renewal marker, TCF-1. Interestingly, the abnormal mitochondrial properties were directly correlated with PD-1 expression in Eµ-TCL1 T-cells. Nanostring significance score analysis of Eµ-TCL1 versus WT CD8+ T-cell RNA revealed upregulation of glycolysis, mitochondrial respiration, T-cell receptor and costimulatory pathways. On the other hand, there was a downregulation in autophagy, AMPK and amino acid transporter pathways. In conclusion, our work characterizes for the first time the metabolic and mitochondrial defects of CD8+ T-cells from Eµ-TCL1 murine model and outlines the correlation of these defects with T-cell exhaustion in CLL. Citation Format: Wael Gamal, Melanie Mediavilla-Varela, Kamira Maharaj, Angimar Uriepero, Vishaal Kunta, Eva Sahakian, Javier Pinilla-Ibarz. Characterization of T-cell metabolic defects in chronic lymphocytic leukemia preclinical model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4843.

Rox Index Dynamics According to High Flow Nasal Cannula Success in Intensive Care Unit Patients with COVID-19-Related Acute Respiratory Failure

High-flow nasal cannula therapy has been shown to be useful in the treatment of patients with acute respiratory failure caused by severe acute respiratory syndrome-coronavirus disease-2. The ROX index can help predict the success of high-flow nasal cannula in coronavirus disease-19-related acute respiratory failure. However, the timing of ROX- index assessment is still unclear to protect the patients from complications due to early or delayed intubation. To evaluate the relation between ROX index patterns within the first 48 hours of the therapy and high-flow nasal cannula success rates. The secondary aim was to determine other possible predictors of high-flow nasal cannula failure. A cross-sectional study. Patients admitted to the intensive care unit between April 2020 and January 2022 with coronavirus disease-19-related acute respiratory failure and treated with high-flow nasal cannula were included in the study. Patients’ demographics, clinical characteristics and laboratory findings at intensive care unit admission; ROX indices at initiation, 2nd, 8th, 12th, 24th and 48th hours of high-flow nasal cannula; and outcomes were recorded. In the study period, 69th patients were managed with high-flow nasal cannula for at least 2 hours. While 24 patients (34.7%) were successfully weaned from high-flow nasal cannula, 45 (65.3%) patients failed. Overall mortality at day 28 was 44.9%. ROX indices were lower in the high-flow nasal cannula failure group through the 12th, 24th, and 48th hours of the therapy, no significant change was observed (P = 0.33). While an overall increase in ROX index patterns were detected in patients weaned from high-flow nasal cannula (P = 0.002). Pairwise analyses revealed that ROX indexes remain stable during the first 8th hours in both groups, then improved to 12th hours of the therapy in successfully high-flow nasal cannula-weaned patients. Dynamic assessments of the ROX indexes could be more suggestive rather than a point assessment to identify patients who would benefit from the high-flow nasal cannula or deteriorate in coronavirus disease-19 related acute respiratory failure.

OUT-OF-HOSPITAL CARDIAC ARREST COMPLICATED WITH ANTERIOR SPINAL ARTERY SYNDROME

Background and objective: The success rate of thrombolytic therapy for patients with ultralong cardiac arrest caused by pulmonary embolism (PE) has been increasing. Thrombolytic timing to reduce the risk of bleeding is critical in preventing anterior spinal artery syndrome (ASAS). Methods: This is a case report of an out-of-hospital cardiac arrest (OHCA) caused by massive PE caused to a patient who received thrombolytic therapy after 140[Formula: see text]min of pre-hospital cardiopulmonary resuscitation (CPR). Results: A 51-year-old female was admitted to the emergency department due to an OHCA, presenting with no vital signs. After 140[Formula: see text]min of CPR, vital signs remained unstable, so thrombolytic therapy with 50-mg Alteplase was performed, spontaneously improving circulation. After admission to the ICU, the muscle strength of the lower limbs was 0 and both shallow and deep reflexes disappeared. After discharge, there was no improvement in the lower limbs at the six-month follow-up. A search of the PubMed database identified 13 cases of OHCA caused by PE who underwent in-hospital CPR before thrombolytic therapy for 2–150[Formula: see text]min, with an 8% incidence of ASAS and a 50% recovery rate. Conclusion: Ultralong CPR for patients with cardiac arrest caused by PE does not affect the outcome of thrombolytic therapy. However, it is necessary to identify these patients early and perform thrombolytic therapy to prevent the complications of CPR as well as the injury to the upper motor neurons caused by thrombosis.

High Expression of PR-A and Low Expression of PR-B is Correlated with Inflammation in Endometrioma Cases

BACKGROUND: Progestin therapy has been commonly used in endometriosis. The regulation of progesterone receptors B (PR-B) greatly affects the success rate of therapy in cases of endometriosis. The presence of tumor necrosis factor (TNF)-a in endometriosis triggers PR-B hypermethylation, decreasing PR-B expression and PR-B/A ratio that induce progesterone resistance. It may also occur in endometrioma. Studies regarding the distribution of PR-A and PR-B with TNF-a expression in endometriosis with endometrioma tissue samples has not been elucidated well. Therefore, this study was conducted to measure and compare the distribution of PR-A and PR-B expression, and to assess the effect of PR-B/A ratio on TNF-a in endometrioma and benign cysts.METHODS: A cross-sectional study was conducted by collecting paraffin blocks of endometriomas and benign cysts as controls, from patients undergoing surgery at Dr. Sardjito Hospital, Yogyakarta. Immunohistochemistry was performed to assess the expressions of PR-A, PR-B, TNF-a and PR-B/A ratio, to compared differences between endometriomas and benign cysts.RESULTS: Twenty-three endometrioma and 22 benign cyst tissue samples were collected. The mean PR-B expression and PR-B/A ratio were found to be lower in endometriomas than benign cysts, and mean expression of PR-A and TNF-a in endometriomas was higher than in benign cysts. However, there were no significant correlations between the expression of PR-A, PR-B, PR-B/A ratio, and TNF-a with endometriosis severity.CONCLUSION: In endometrioma cases, the expression of PR-A and TNF-a was higher, while the expression of PR-B and PR-B/A ratio was lower. However, there was no significant relationship between the ratio of PR-B/A and TNF-a.KEYWORDS: progesterone receptor, tumor necrosis factor-alpha, endometriosis, endometrioma, benign cyst, ovarian cyst

Ethical Need for a Fertility Decision-Aid for Transgender Adults of Reproductive Age

Ethical Need for a Fertility Decision-Aid for Transgender Adults of Reproductive Age

Porous Framework Materials for Bioimaging and Cancer Therapy.

Cancer remains one of the most pressing diseases in the world. Traditional treatments, including surgery, chemotherapy, and radiotherapy still show certain limitations. Recently, numerous cancer treatments have been proposed in combination with novel materials, such as photothermal therapy, chemodynamic therapy, immunotherapy, and a combination of therapeutic approaches. These new methods have shown significant advantages in reducing side effects and synergistically enhancing anti-cancer efficacy. In addition to the above approaches, early diagnosis and in situ monitoring of lesion areas are also important for reducing side effects and improving the success rate of cancer therapy. This depends on the decent use of bioimaging technology. In this review, we mainly summarize the recent advances in porous framework materials for bioimaging and cancer therapy. In addition, we present future challenges relating to bioimaging and cancer therapy based on porous framework materials.

Leech therapy for the treatment of venous congestion in digital re-plants and revascularizations

Aims: Leech therapy was first used in Egypt around 1500 BC to treat a range of ailments from nosebleeds to gout. Medicinal leeches have been part of the therapeutic armamenterium of hand surgeons for more than 60 years. Venous congestion after digital replantation or revascularization threatens digit survival in theimmediate postoperative period. External bloodletting, including leech therapy, provides a central role in salvage of the congested finger. Although there have been previous studies few published articles and no consensus guidelines have discussed the weaning of leeches in the postoperative period.describing the initiation of leech therapy for digits experiencing venous insufficiency Methods: Analyzing articles on treatment and follow-up after finger replantation published between 2000 and 2022 on the treatment of venous congestion after finger replantation and revascularization. We conducted a systematic review, taking into account the studies that applied leech therapy. The collected data revealed the relevant indications, treatment procedures, efficacy, adjuvant treatments, side effects. Results: For this indication, the success rate of leech therapy ranged from 65 to 85% (83.7% in our series) according to the situations encountered. Optimal frequency of application ranged from 2 to 8 hours, while average overall duration ranged from 4 to 10 days. Antibiotic prophylaxis against Aeromonas is highly advisable. A ciprofloxacin and trimethoprim-sulfametoxazole combination currently appears as the most relevant prophylactic antibiotherapy. Conclusion: Hirudotherapy is a reliable treatment in cases of patent venous insufficiency of only artery only digit replantation. Even though the relevant literature is highly heterogeneous, we have attempted to put forward a specific protocol bringing together dosage, delivery route, frequency of administration and appropriate prophylactic antibiotherapy

Effect of Neuro-Adaptive Electrostimulation Therapy versus Sham for Refractory Urge Urinary Incontinence Due to Overactive Bladder: A Randomized Single-Blinded Trial.

This randomized clinical trial evaluates the success rate of neuro-adaptive therapy (NAT), applied with a specific neuro-adaptive regulator device, the Self-Controlled Electro Neuro-Adaptive Regulation (SCENAR), versus a sham for urge incontinence due to an overactive bladder (OAB). From February 2019 to May 2021, 66 patients were recruited. All subjects were randomized 1:1 at the first intervention visit to the NAT or sham procedure. Inclusion criteria were females between 18 and 80 years old with leakages due to an overactive bladder with unresponsiveness to medical therapy. Subjects were scheduled to receive up to eight weekly 20 min intervention sessions to obtain a complete (CR) or partial response (PR). Patients with no response after three sessions were considered as a failure. The primary end point of this trial was to assess the efficacy of NAT compared to an inactive sham intervention, evaluated 1 month after the last session. Analysis showed 23 (70%) patients responded (20 complete and 3 partial response) in the NAT group compared to 16 (48%) patients (all complete response) in the placebo arm (p = 0.014). Significant differences were maintained after the intervention, with persistent response at 3 months in 19 (58%) patients after active treatment and 14 (42%) after the placebo (p < 0.001), and at 6 months in 18 (55%) vs. 11 (33%) (p = 0.022), respectively. The number of sessions to achieve CR was similar in both arms, with 4.3 ± 1.9 in NAT and 3.9 ± 1.8 in the sham group (NS). Significant differences were observed between both groups for patients' satisfaction (p = 0.01). The binary model selected age as a predictor of response at the last follow-up. The odds ratio indicates that each year of increase in age, the probability of a positive response to treatment at 6 months decreases 0.95 (95% CI 0.9-0.99) times (p = 0.03). In conclusion, this pilot randomized trial gives evidence that neuro-adaptive electrostimulation is effective to treat refractory urge urinary incontinence due to OAB. The security and long-term efficacy of this treatment merits further evaluation. Moreover, its favorable profile and the economic advantages of the device make the evaluation of this promising technique mandatory in a primary therapeutic scenario.

The Outcome of Prescribing Antibiotics for the Management of Patients with Endodontic Infections.

This study aimed to evaluate the efficacy and duration of antibiotic therapy with different regi- mens of antibiotics for patients presenting with primary and secondary endodontic infections. In a case series outcome study, all patients needing antibiotics due to endodontic infection were included. In patients with no history of hypersensitivity to penicillin, amoxicillin was used as the first-line antibiotic, followed by adding metronidazole if the symptoms did not show signs of recovery during the first 24 hours after prescribing the medication. If a patient did not respond to the combination of amoxicillin and metronidazole, amoxicillin was substituted with a parental penicillin G procaine. Patients who had sensitivity to penicillin received clindamycin. In cases where drainage was possible, the effect of the procedure on the success rate of antibiotic therapy was evaluated. All patients were asked to continue taking the antibiotic for up to two days following the relief of symptoms. Data were analysed by Chi-square, Fisher exact test, Indepen- dent t-test, and One-way ANOVA. Over a period of 6 years, 97 patients were eligible to be included in this study. In patients with no history of sensitivity to penicillin (95.9% of the patients), 52.7% of patients on amoxicillin and 43% of patients on amoxicillin plus metronidazole overcame the endodontic infections. In addition, drainage significantly increased the success rate of antibiotic therapy when amoxicillin was prescribed (p=0.046). There were no significant differences between the gender, age, type of tooth, need for primary or secondary endodontic treatment, previous history of infection, need for drainage or duration of antibiotic consumption (p>0.05), and the success of antibiotic prescription. However, patients who received a single antibiotic (either amoxi- cillin or clindamycin) had significantly shorter average times for the recovery of symptoms (p<0.05). Amoxicillin helped patients recover from endodontic infection symptoms in more than half of the cases. However, it is necessary to monitor the patients to understand if they should be needed further treatment, such as another antibiotic or drainage. (EEJ-2022-11-138).

Pulp Therapy of Primary Dentition; its Relevance despite Insufficient Histological Evidence: A Review.

Pulp treatment in primary dentition is generally divided into vital and non-vital pulp therapies and assists in the preservation of pulpally involved primary teeth in the dental arch until the affected tooth naturally exfoliates. The success of pulp therapies depends on several factors; e.g. proper case selection, accurate diagnosis and good coronal seal. To date, studies on the success and failure rates of pulp treatments are based on clinical signs and symptoms, radiographic findings and histological analysis. However, the clinical and radiographic evidence may not completely portray the true status of the dental pulp. Histological evidence remains the gold standard in the assessment of pulp condition, whether it is in a healthy or adverse state. The aims of the current research were to summarise the treatment outcomes of pulp therapy in primary dentition based on clinical, radiographic and histological criteria, and to support its relevance in the presence of limited histological evidence to measure authentic treatment success. An electronic database search of dental literature from 1990 to 2022 was carried out using the MEDLINE, i.e. PubMed, database. Current dental literature showed that the success rates of primary tooth pulp therapy are high. The obtained results were based largely on clinical and radiographic studies with narrow histological investigations to assess the treatment outcome(s) of pulp therapy in primary dentition. Despite the scarcity of histological evidence, pulp therapies in primary teeth are still practical due to their statistically empirical success compared to their failure. Consequently, pulp therapy of primary dentition is still relevant, and should continue to be indicated as an important treatment option.

Adequate amounts of probiotics increase the success rate of Helicobacter pylori eradication therapy in children.

Adequate amounts of probiotics increase the success rate of Helicobacter pylori eradication therapy in children.

Endodontic Treatment in Elderly Patients: Success Rates, Satisfaction, and Outcomes

As the global population continues to age, addressing the nuances of healthcare for elderly individuals becomes increasingly crucial. Within the realm of dentistry, endodontic treatment, or root canal therapy, holds significant importance as it preserves natural teeth, alleviates pain, and enhances oral health. The success rates of endodontic therapy in the elderly are influenced by factors such as dentist experience, patient compliance, and case complexity. Patient satisfaction in this demographic is multifaceted, encompassing pain management, clinical success, communication, and emotional well-being. Clinical outcomes profoundly impact overall oral health and quality of life, including pain relief, infection control, and the preservation of natural dentition. While age-related changes and medical comorbidities introduce challenges, they do not inherently hinder treatment success. This review emphasizes that endodontic therapy remains a viable and effective option for elderly patients, with individualized care plans and patient-centered approaches being paramount. As the elderly population continues to grow, further research and refined practices are essential to meet their evolving dental needs effectively. Dental professionals must remain attuned to the unique challenges and priorities of elderly individuals to deliver highquality endodontic care.

Stem-cell therapy in stress urinary incontinence: A review.

The incidence of urinary incontinence (UI) is approximately 10%-40% in women, affecting one to two hundred million women worldwide. Stress UI (SUI) is characterized by involuntary urination due to increased abdominal stress and urine leakage without bladder contraction. Surgical treatments include midurethral slings, bulking agents, and Burch colposuspension to restore urethral continence. Nevertheless, an optimal treatment for all types of incontinence has not yet been established. Stem-cell therapy has emerged as a novel treatment for many diseases. Stem cells can self-renew and can differentiate into other cell types. Adult stem cells are suitable for clinical applications because they can be easily obtained noninvasively or minimal invasively. Stem-cell therapy for SUI has been studied preclinically and clinically. Muscle-derived progenitors have been used to treat SUI by promoting the regeneration of rhabdomyosphincters. The human trial used transurethral injection of autologous muscle-derived stem cells to improve sphincter contractility and function. Other sources of stem cells have also been studied in SUI treatment, such as umbilical cord blood, amniotic fluid, bone marrow, urine, and adipose tissue. The success rate of stem-cell therapy for SUI ranges from 13% to 100%. This review aimed to summarize the current status of stem-cell treatments for SUI, with respect to clinical trials, cell types, transplantation routes, and dosage volume and frequency.

Lung Cancer Classification in Histopathology Images Using Multiresolution Efficient Nets.

Histopathological images are very effective for investigating the status of various biological structures and diagnosing diseases like cancer. In addition, digital histopathology increases diagnosis precision and provides better image quality and more detail for the pathologist with multiple viewing options and team annotations. As a result of the benefits above, faster treatment is available, increasing therapy success rates and patient recovery and survival chances. However, the present manual examination of these images is tedious and time-consuming for pathologists. Therefore, reliable automated techniques are needed to effectively classify normal and malignant cancer images. This paper applied a deep learning approach, namely, EfficientNet and its variants from B0 to B7. We used different image resolutions for each model, from 224 × 224 pixels to 600 × 600 pixels. We also applied transfer learning and parameter tuning techniques to improve the results and overcome the overfitting problem. We collected the dataset from the Lung and Colon Cancer Histopathological Image LC25000 image dataset. The dataset acquisition consists of 25,000 histopathology images of five classes (lung adenocarcinoma, lung squamous cell carcinoma, benign lung tissue, colon adenocarcinoma, and colon benign tissue). Then, we performed preprocessing on the dataset to remove the noisy images and bring them into a standard format. The model's performance was evaluated in terms of classification accuracy and loss. We have achieved good accuracy results for all variants; however, the results of EfficientNetB2 stand excellent, with an accuracy of 97% for 260 × 260 pixels resolution images.

Sequential treatment with transurethral resection and hormonal therapy for bladder endometriosis of vesicoureteric junction

Objective: To estimate the efficacy of sequential treatment of bladder endometriosis (BE) of the vesicoureteric junction using transurethral resection (TUR) and hormonal therapy. Design: Case report. Setting: Private multispecialty hospital. Patient: A multiparous woman presented with perimenstrual lower urinary tract symptoms, cyclic chronic pelvic pain, and left loin pain. Intervention[s]: Ultrasonography revealed marked left renal dilatation. Computed tomography confirmed the presence of a bladder mass. A diagnostic cystoscopy revealed compression of the left vesicoureteral junction. Complete TUR BE with release of chocolate material during resection, followed by ureteric double J stent insertion for 3 months, was performed. Histopathology confirmed the diagnosis of BE, followed by adjuvant hormonal therapy (dienogest) for 3 months. Followup for about 2 years revealed complete relief of the symptoms without any recurrence. Main Outcome Measure[s]. Success and recurrence rates of sequential TUR and hormonal therapy of BE of the vesicoureteric junction. Result[s]. TUR BE followed by adjuvant hormonal therapy was very effective in eradicating BE of the vesicoureteric junction in a safe manner without recurrence on follow-up for 2 years. Conclusion[s]. BE of the vesicoureteric junction can be properly treated by sequential TUR and hormonal therapy without recurrence over a 2-year follow-up.

Increased protein phosphatase 5 expression in inflammation-induced left ventricular dysfunction in rats

Titin phosphorylation contributes to left ventricular (LV) diastolic dysfunction. The independent effects of inflammation on the molecular pathways that regulate titin phosphorylation are unclear. We investigated the effects of collagen-induced inflammation and subsequent tumor necrosis factor-α (TNF-α) inhibition on mRNA expression of genes involved in regulating titin phosphorylation in 70 Sprague-Dawley rats. LV diastolic function was assessed with echocardiography. Circulating inflammatory markers were quantified by enzyme-linked immunosorbent assay and relative LV gene expression was assessed by Taqman® polymerase chain reaction. Differences in normally distributed variables between the groups were determined by two-way analysis of variance (ANOVA), followed by Tukey post-hoc tests. For non-normally distributed variables, group differences were determined by Kruskal-Wallis tests. Collagen inoculation increased LV relative mRNA expression of vascular cell adhesion molecule 1 (VCAM1), pentraxin 3 (PTX3), and inducible nitric oxide synthase (iNOS) compared to controls, indicating local microvascular inflammation. Collagen inoculation decreased soluble guanylate cyclase alpha-2 (sGCα2) and soluble guanylate cyclase beta-2 (sGCβ2) expression, suggesting downregulation of nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling. Inhibiting TNF-α prevented collagen-induced changes in VCAM1, iNOS, sGCα2 and sGCβ2 expression. Collagen inoculation increased protein phosphatase 5 (PP5) expression. Like LV diastolic dysfunction, increased PP5 expression was not prevented by TNF-α inhibition. Inflammation-induced LV diastolic dysfunction may be mediated by a TNF-α-independent increase in PP5 expression and dephosphorylation of the N2-Bus stretch element of titin, rather than by TNF-α-induced downregulation of NO-sGC-cGMP pathway-dependent titin phosphorylation. The steady rise in number of patients with inflammation-induced diastolic dysfunction, coupled with low success rates of current therapies warrants a better understanding of the systemic signals and molecular pathways responsible for decreased titin phosphorylation in development of LV diastolic dysfunction. The therapeutic potential of inhibiting PP5 upregulation in LV diastolic dysfunction requires investigation.

Low-Intensity Pulsed Ultrasound Therapy in Patients With Post-traumatic Delayed Union and Non-union.

Background Fracture non-union can lead to significant patient morbidity with poor quality of life. Due to the cost, complexity, and potential risks of revision surgery, there has been an increased popularity in the use of low-intensity pulsed ultrasound therapy (LIPUS), which accelerates and promotes bone consolidation. There is an ongoing debate regarding the use and efficacy of LIPUS in delayed union and non-union. This study aims to assess the success rate of LIPUS therapy in patients treated for delayed and non-union fractures, explicitly focusing on the impact of patient co-morbidities and fracture characteristics. Method A retrospective observational study was performed of all consecutive patients who received LIPUS therapy in a single institution from January 2016 to September 2022. Of 127 identified patients, only 99 patients met our inclusion criteria. Data collection entailed reviewing the clinical notes to assess patients' sex, age, co-morbidities, initial treatment method, time to initiate LIPUS, whether a CT was performed to diagnose non-union, time to union and whether revision surgery was needed. Two independent senior orthopedic doctors reviewed the patients' radiographs, measured the interfragmentary bone gap of all fractures, and assessed whether the radiographic union was achieved. Results The mean age of the included patients was 52.5 (SD±16.9) years with a male-to-female ratio of 1:1.6. At initial presentation, 65 (out of 99) patients were treated surgically, whereas the rest were managed conservatively. 80.8% of patients developed atrophic non-union. All 99 included patients were fitted with LIPUS once delayed/ non-union was diagnosed; the average time to fitting was 5.1 (SD±3.9) months. Of these, 61.6% of patients were successfully treated with LIPUS with a clinical and radiological union at an average of 4.3 (SD±1.9) months. The rest of the patients needed further surgical intervention due to ongoing non-union. The interfragmentary bone gap was the only statistically significant factor influencing the success of LIPUS therapy (p=0.003). In contrast, no statistically significant association was identified between the outcome of LIPUS therapy and the patient's age, sex, diabetes, and smoking status. Conclusion This study demonstrated a 61.6% progression to union rate of patients treated with LIPUS therapy for delayed union and non-union. The interfragmentary bone gap was identified as the only statistically significant factor influencing the success of LIPUS therapy. In the current climate post-lockdown and with ongoing Covid 19 outbreaks impacting elective waiting lists negatively, there is increased value and demand for non-surgical treatment options. LIPUS therapy represents an important complementary non-surgical and low-risk treatment pathway for delayed union and non-union.

Fetal arrhythmias: Ten years' experience and review of the literature.

Fetal arrhythmias complicate 1-2% of all pregnancies. Ultrasound evaluation and Doppler technology are indispensable in both diagnosis and management. Digoxin, sotalol, flecainide and amiodarone are widely accepted antiarrhythmic agents that are frequently. We reviewed the maternal and fetal outcomes in cases with fetal arrhythmia in a tertiary care center in the last decade. Fetal arrhythmias were classified under three main groups: Irregular rhythms, tachyarrhythmia and bradyarrhythmia. Detailed anatomical evaluation and fetal echocardiography were performed in all cases to determine whether a structural cardiac and extracardiac anomaly accompanied fetal arrhythmia and the type of fetal arrhythmia. Digoxin was started primarily as first-line therapy in patients with persistent fetal tachyarrhythmia. In cases, not responding to digoxin, other antiarrhythmic agents (sotalol, flecainide) were combined with treatment without discontinuing digoxin. Fetal arrhythmia was detected in 36 cases during the study period. 50% (n=18/36) of the cases had supraventricular tachycardia, whereas 28% (n=10/36) of them were fetal bradyarrhythmia and 22% (n=8/36) of them were with various irregular rhythms. Transplacental therapy was initiated in 13 patients with persistent supraventricular tachycardia and atrial flutter regardless of the presence of hydrops. The success rate in transplacental therapy was 77% (n=10/13). Successful transplacental therapy was achieved in approximately 80% of cases and delivery could be postponed to advanced gestational weeks, confirming the crucial role of this treatment for the management of tachyarrhythmia.

Investigation on Utility of Some Novel Terpenes on Transungual Delivery of Terbinafine for the Management of Onychomycosis.

Onychomycosis is a fungal disorder of the nail which afflicts 5% of the population worldwide. The disease is strenuous to cure as it is chronic, hard to eliminate and tends to recur. Topical therapy is at the forefront for the treatment of many disorders of nail. However, the success rate of topical therapy has been halted owing to the poor permeation of topical therapeutics across densely keratinized nail barrier. Therefore, ungual drug permeation must be improved for an effective topical therapy. An approach to achieve this goal would be the use of terpenes from natural sources as potential penetration enhancers. This study is aimed to explore the effectiveness of some novel terpenes as potential penetration enhancers on transungual delivery of terbinafine. Ex-vivo permeation studies were performed by sopping the nail clippings of healthy human volunteers in control and working solutions containing terbinafine (5mg/ml) per se and terbinafine (5mg/ml) with 6% of each terpenes including lavandulol, safranal, rose oxide, limonene, 3-methyl-2-butene-1-ol, and linalool respectively for 48 hours. The terbinafine concentration in nail samples was determined using a HPLC (High Performance Liquid Chromatography method. Statistical analysis showed that studied terpenes increase transungual penetration of terbinafine in the following order: linalool > rose oxide > 3-methyl-2-butene-1-ol > safranal > limonene > lavandulol acetate. Accordingly, linalool was found to be the most effective penetration enhancer for the transungual delivery of terbinafine. It is concluded that linalool can be used as safe and potential penetration enhancer for enhancing the transungual delivery of terbinafine for onychomycosis.

The Potential Application of Human Gingival Fibroblast-Conditioned Media in Pulp Regeneration: An In Vitro Study.

Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.