Functional Improvement Research Articles

EXTENSIVE SUBRETINAL FIBROSIS ASSOCIATED WITH PSEUDOXANTHOMA ELASTICUM.

The purpose of this study was to report an unusual case of pseudoxanthoma elasticum presenting with an inflammatory phenotype associated with atypical and rapidly progressive subretinal fibrosis. This was an observational case report. A patient with a history of pseudoxanthoma elasticum presented with rapidly progressive subretinal fibrosis, particularly in the left eye, over the course of one year. The patient was noted at presentation to have intraocular inflammation, outer retinal attenuation, multifocal choroiditis-like lesions, and intraretinal fluid (in the absence of obvious clinical or angiographic signs of exudative choroidal neovascular membranes). An ocular inflammatory phenotype was diagnosed, and the patient was treated with a combination of local steroids and systemic corticosteroids/immunomodulatory agents. After initiation of these agents, the patient demonstrated functional and structural improvement, with partial outer retinal reconstitution, decreased intraretinal fluid, and lack of further progression of subretinal fibrosis. This report describes an inflammatory phenotype of pseudoxanthoma elasticum associated with severe and atypical subretinal fibrosis. This case expands upon the currently known spectrum of inflammatory phenotypes associated with pseudoxanthoma elasticum. Treatment with corticosteroids or immunomodulatory treatment should be considered in similar cases.

Correlation of imaging characteristics of degenerative cervical myelopathy and the surgical approach with improvement for postoperative neck pain and neural function: a retrospective cohort study

Correlation of imaging characteristics of degenerative cervical myelopathy and the surgical approach with improvement for postoperative neck pain and neural function: a retrospective cohort study

Electronic Immunization Registry in Rwanda: Qualitative Study of Health Worker Experiences.

Monitoring childhood immunization programs is essential for health systems. Despite the introduction of an electronic immunization registry called e-Tracker in Rwanda, challenges such as lacking population denominators persist, leading to implausible reports of coverage rates of more than 100%. This study aimed to assess the extent to which the immunization e-Tracker responds to stakeholders' needs and identify key areas for improvement. In-depth interviews were conducted with all levels of e-Tracker users including immunization nurses, data managers, and supervisors from health facilities in 5 districts of Rwanda. We used an interview guide based on the constructs of the Human, Organization, and Technology-Fit (HOT-Fit) framework, and we analyzed and summarized our findings using the framework. Immunization nurses reported using the e-Tracker as a secondary data entry tool in addition to paper-based forms, which resulted in considerable dissatisfaction among nurses. While users acknowledged the potential of a digital tool compared to paper-based systems, they also reported the need for improvement of functionalities to support their work, such as digital client appointment lists, lists of defaulters, search and register functions, automated monthly reports, and linkages to birth notifications and the national identity system. Reducing dual documentation for users can improve e-Tracker use and user satisfaction. Our findings can help identify additional digital health interventions to support and strengthen the health information system for the immunization program.

Effect of human heart valve-derived ECM and NP/PCL electrospun nanofibrous sheet on mice bone marrow mononuclear cells and cardiac repair

BackgroundBiomaterials can improve cardiac repair combined with transplantation of bone marrow mononuclear cells (BMMNCs). In this study, we compared the phenotype and cardiac repair between human heart valve-derived scaffold (hHVS) and natural protein/polycaprolactone (NP/PCL) anchored BMNNCs. Methods and resultsBMMNCs were obtained from mice five days following myocardial infarction. Subsequently, BMMNCs were separately cultured on hHVS and PCL. Proliferation and cardiomyogenic differentiation were detected in vitro. Cardiac function was measured after transplantation of cell-seeded cardiac patch on MI mice. After that, the BMMNCs were collected for mRNA sequencing after culturing on the scaffolds. Upon anchoring onto hHVS or PCL, BMMNCs exhibited an increased capacity for proliferation in vitro, however, the cells on hHVS exhibited superior cardiomyogenic differentiation ability. Moreover, both BMMNCs-seeded biomaterials effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. Cell-seeded hHVS was superior to cell-seeded PCL. ConclusionBMMNCs on hHVS showed better capacity in both cell cardiac repairing and improvement for cardiac function than on PCL. Compared with seeded onto PCL, BMMNCs on hHVS had 253 genes up regulated and 189 genes down regulated. The reason for hHVS’ better performance than PCL as a scaffold for BMMNCs might be due to the fact that optimized method of decellularization let more cytokines in ECM retained.

Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters

BackgroundBalloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We...

Characterizing the Impact of Facial Rehabilitation on Acute Facial Paralysis.

Evidence on facial rehabilitation therapy (FRT) for acute facial paralysis (FP) remains limited. We present a retrospective review of patients with acute FP who have received FRT with physical therapists within one (1) year of FP onset as determined by Sunnybrook Facial Grading Scale (SFGS) composite scores. 702 patients with a clinical diagnosis of FP were referred to a university rehabilitation program between January 1, 2015, and January 1, 2022. Seventy-six patients met the criteria, defined as FP diagnosis <12 months before FRT initiation, ≥3 therapy sessions, and sufficient follow-up data. Average number of treatment sessions between SFGS scores was 7.7. History of cancer, sex, number of treatment sessions, and initial SFGS score were correlated with change in SFGS. Time to treatment was not correlated with change in SFGS score. SFGS improved with each additional treatment session (p<.01). Each additional point in the initial SFGS was correlated with less change in the final SFGS score (p<.01). FRT can provide meaningful improvement in functionality for patients with acute FP, regardless of time to treatment. Furthermore, patients who present with poorer functionality at baseline and those who undergo more treatment are most likely to see SFGS improvement. Research comparing the effect of facial rehabilitation compared to other treatment modalities and to a control cohort is warranted.

Disentangling the Diagnoses of Psychotic Depression, Catatonia, Neurocognitive Disorders, and Delirium: A Multidisciplinary Approach

An ambiguous clinical presentation can create diagnostic uncertainty, leading to delays in effective interventions and increasing the likelihood of adverse clinical outcomes. Unfortunately, many psychiatric conditions share overlapping clinical symptoms. Psychotic depression, catatonia, neurocognitive disorders, and delirium are all examples of distinct clinical conditions with overlapping symptomatology, and all require decidedly different therapeutic interventions. While much literature is devoted to the diagnostic criteria and management of these clinical conditions, little is dedicated to the challenge of disentangling these diagnoses when faced with a complex clinical presentation.We present here a complicated psychiatric inpatient hospitalization of a 77-year-old male who exemplified this diagnostic challenge. He primarily presented with severely depressed mood and decreased functionality, remaining in bed for much of the day with little attention to basic hygiene and oral intake. While records from a recent outside hospitalization carried a historical diagnosis of catatonia, his moderate level of engagement with providers and somatic delusion of disseminated prostate cancer suggested an alternate diagnosis of psychotic depression. However, before a diagnostic conclusion could be reached, other clinical characteristics surfaced. Following a singular administration of olanzapine shortly after his initial assessment, he developed Lilliputian hallucinations, prominent parkinsonism, and significantly altered mentation.Neuroleptic sensitivity raised clinical suspicion for an underlying neurocognitive disorder such as dementia with Lewy bodies, and a consult was placed to the neuropsychology service. While dementia could not be fully ruled out, they did recommend additional workup to rule out herpes simplex encephalitis, autoimmune limbic encephalitis, and paraneoplastic syndromes. After his MRI imaging revealed moderate microvascular ischemic changes, a true multidisciplinary approach to care was taken, as neurology was consulted to also help narrow the differential. An EEG was unremarkable and a serum encephalitis panel was also unremarkable. Olanzapine was discontinued with significant improvement in parkinsonism and cognition; however, severe neurovegetative symptoms and somatic and nihilistic delusions persisted. While antipsychotics remained clinically indicated for a suspected depression with psychotic features, caution was taken due to established neuroleptic sensitivity, subtle catatonic features, and the related risks of neuroleptic malignant syndrome. Ultimately, low-dose quetiapine was initiated with some benefit; however, he continued to remain acutely depressed and withdrawn with prominent negativism. Trials with benzodiazepines for these catatonic features were also approached with caution to avoid potential risks of delirium.Over time, a multidisciplinary approach to psychopharmacologic interventions and medication trials led the team to a principal diagnosis of major depressive disorder with psychotic features and subtle catatonia. The abrupt changes observed early in the hospital course were determined to be related to olanzapine-induced anticholinergic delirium. With greater diagnostic certainty, the team was able to counsel the patient and family about the importance of pursuing electroconvulsive therapy (ECT). The patient's cardiovascular risk factors and known microvascular changes were considered in the determination of the appropriateness for ECT. After starting ECT, he was immediately noted to have objective improvement, and following his fifth treatment, he was deemed appropriate for discharge after exhibiting significant improvement in depression and functionality and reporting near-resolution of somatic delusions. He was able to complete ECT on an outpatient basis and follow-up visits note durable improvements in mood, functionality, and quality of life, continuing to enjoy an active lifestyle of socializing with family and playing tennis. We use this case to further explore the clinical challenges that stem from the symptomatic similarity between psychotic depression, catatonia, neurocognitive disorders, and delirium and discuss optimal therapeutic approaches when the presentation appears complex and equivocal.

Patient Risk-Benefit Preferences for Transcatheter Versus Surgical Mitral Valve Repair.

Transcatheter edge-to-edge repair (TEER) of mitral regurgitation is less invasive than surgery but has greater 5-year mortality and reintervention risks, and leads to smaller improvements in physical functioning. The study objective was to quantify patient preferences for risk-benefit trade-offs associated with TEER and surgery. A discrete choice experiment survey was administered to patients with mitral regurgitation. Attributes included procedure type; 30-day mortality risk; 5-year mortality risk and physical functioning for 5 years; number of hospitalizations in the next 5 years; and risk of additional surgery in the next 5 years. A mixed-logit regression model was fit to estimate preference weights. Two hundred one individuals completed the survey: 63% were female and mean age was 74 years. On average, respondents preferred TEER over surgery. To undergo a less invasive procedure (ie, TEER), respondents would accept up to a 13.3% (95% CI, 8.7%-18.5%) increase in reintervention risk above a baseline of 10%, 4.6 (95% CI, 3.1-6.2) more hospitalizations above a baseline of 1, a 10.7% (95% CI, 6.5%-14.5%) increase in 5-year mortality risk above a baseline of 20%, or more limited physical functioning representing nearly 1 New York Heart Association class (0.7 [95% CI, 0.4-1.1]) over 5 years. Patients in general preferred TEER over surgery. When holding constant all other factors, a functional improvement from New York Heart Association class III to class I maintained over 5 years would be needed, on average, for patients to prefer surgery over TEER.

Guillain-Barre in the long-term acute care hospital setting: Ventilation does not prolong stay

Objective Guillain-Barre Syndrome (GBS) is a rare acute inflammatory demyelinating polyneuropathy, resulting in loss of muscle function and potentially respiratory failure requiring prolonged mechanical ventilation. Data describing the demographics and outcomes of patients with severe GBS requiring prolonged ventilation in the long-term acute care hospital (LTACH) setting is limited. We hypothesized that patients with GBS requiring prolonged mechanical ventilation require longer lengths of stay in an LTACH and are discharged with poorer functional status than GBS patients who do not require mechanical ventilation. Design, Setting, and Participants We conducted a retrospective study of GBS patients admitted over a 9-year period at an independent, large LTACH and compared ventilated versus non-ventilated GBS patients’ lengths of stay and functional ability at the time of admission and discharge. Interventions Not Applicable Main Outcome Measures and Results We found no significant difference in mean (standard error of means) lengths of stay between ventilated and non-ventilated GBS patients admitted to an LTACH (48.4 (± 8.0) vs. 38.8 (± 5.7) days, P 0.37). We also found that ventilated patients with GBS were discharged from an LTACH with similar functional ability than non-ventilated GBS patients (4.5 vs. 4.0, P 0.43 on 10 ft walk; 4.7 vs. 4.5 on P 0.70; 5.0 vs. 4.2, P 0.21 on 150 ft walk). Conclusion These findings suggest that GBS patients suffering from prolonged mechanical ventilation may expect similar lengths of stay in an LTACH as non-ventilated GBS patients and a similar or greater rate of functional improvement during their stay. These data support admission of chronically ventilated GBS patients to an LTACH for ongoing care after their acute care without the anticipation of greater length of stay or less rehabilitation outcomes with respect to non-ventilated GBS patients. Keywords: Guillain-Barre Syndrome, Assisted Ventilation, Pulmonary Rehabilitation, LTACH, Critical Care

Accelerating HEP simulations with Neural Importance Sampling

Many high-energy-physics (HEP) simulations for the LHC rely on Monte Carlo using importance sampling by means of the VEGAS algorithm. However, complex high-precision calculations have become a challenge for the standard toolbox, as this approach suffers from poor performance in complex cases. As a result, there has been keen interest in HEP for modern machine learning to power adaptive sampling. While previous studies have shown the potential of normalizing-flow-powered neural importance sampling (NIS) over VEGAS, there remains a gap in accessible tools tailored for non-experts. In response, we introduce ZüNIS, a fully automated NIS library designed to bridge this divide, while at the same time providing the infrastructure to customise the algorithm for dealing with challenging tasks. After a general introduction on NIS, we first show how to extend the original formulation of NIS to reuse samples over multiple gradient steps while guaranteeing a stable training, yielding a significant improvement for slow functions. Next, we introduce the structure of the library, which can be used by non-experts with minimal effort and is extensivly documented, which is crucial to become a mature tool for the wider HEP public. We present systematic benchmark results on both toy and physics examples, and stress the benefit of providing different survey strategies, which allows higher performance in challenging cases. We show that ZüNIS shows high performance on a range of problems with limited fine-tuning.

Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case.

Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke. Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE). VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas.

We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using three main classes and a total of five subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320. All patients with at least one available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation. Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%) and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (p=0.061). All class 1 patients (2/2), 75% of class 2 patients (3/4) and only 10% of class 3 patients (1/10) had clinical benefit. Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials.

Community-based rehabilitation services implemented by multidisciplinary teams among adults with stroke: a scoping review with a focus on Chinese experience

BackgroundDespite the growing interest in hospital rehabilitation services for communities, studies on existing community-based rehabilitation (CBR) services remain scarce owing to limitations in the development of community health services and regional cultural diversity. As a guaranteed measure for ensuring the quality of rehabilitation services and achieving the desired service outcomes, clear roles and responsibilities in multidisciplinary teams and effective service delivery are particularly important.ObjectiveThis scoping review aimed to determine the scope of community stroke rehabilitation programs involving existing multidisciplinary teams and to analyze the implementation content and implementers’ functional roles to provide guidance for future CBR programs.MethodsThe scoping review design followed the methodology of the Joanna Briggs Institute and was based on the normative scoping review framework proposed by Arksey and O’Malley. The comprehensive CBR framework was proposed by World Health Organization-guided data charting and analysis.ResultsOf the 22,849 identified citations, 74 studies were included, consisting of 6,809 patients with stroke and 49 primary caregivers, most of whom were from China. The most common working mode in CBR programs was a dual approach involving both healthcare professionals in medical institutions and community healthcare professionals. The number of programs in each discipline was in the following descending order: nursing, medical care, rehabilitation, psychology, nutrition, and public health. Among these, multidisciplinary teams comprising medical, nursing, and rehabilitation disciplines were the most common, with a total of 29 programs. Disciplinary members were mainly responsible for implementing their respective disciplinary content, with physicians providing guidance for the programs. More than 82.4% of the studies reported 2–4 intervention strategies. The intervention forms of rehabilitation content were the most diverse, whereas preventive interventions were more homogeneous than others. Physical function and socio-psychological measurements were the most commonly reported outcomes.ConclusionCBR services implemented by multidisciplinary teams can effectively achieve functional and emotional improvement in patients with stroke, and nurses are the most involved in implementation, especially in community settings. The results further emphasize the importance of strengthening the exploration of nurses’ maximum potential to implement CBR plans in future practice.Trial registrationThe registration information for this scoping review can be found at osf.io/pv7tg.

Generalizable anchor aptamer strategy for loading nucleic acid therapeutics on exosomes.

Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.

Reprogramming of astrocytes to neuronal-like cells in spinal cord injury: a systematic review.

A Systematic Review OBJECTIVES: To determine the therapeutic efficacy of in vivo reprogramming of astrocytes into neuronal-like cells in animal models of spinal cord injury (SCI). PRISMA 2020 guidelines were utilized, and search engines Medline, Web of Science, Scopus, and Embase until June 2023 were used. Studies that examined the effects of converting astrocytes into neuron-like cells with any vector in all animal models were included, while conversion from other cells except for spinal astrocytes, chemical mechanisms to provide SCI models, brain injury population, and conversion without in-vivo experience were excluded. The risk of bias was calculated independently. 5302 manuscripts were initially identified and after eligibility assessment, 43 studies were included for full-text analysis. After final analysis, 13 manuscripts were included. All were graded as high-quality assessments. The transduction factors Sox2, Oct4, Klf4, fibroblast growth factor 4 (Fgf4) antibody, neurogenic differentiation 1 (Neurod1), zinc finger protein 521 (Zfp521), ginsenoside Rg1, and small molecules (LDN193189, CHIR99021, and DAPT) could effectively reprogramme astrocytes into neuron-like cells. The process was enhanced by p21-p53, or Notch signaling knockout, valproic acid, or chondroitin sulfate proteoglycan inhibitors. The type of mature neurons was both excitatory and inhibitory. Astrocyte reprogramming to neuronal-like cells in an animal model after SCI appears promising. The molecular and functional improvements after astrocyte reprogramming were demonstrated in vivo, and further investigation is required in this field.

Evaluation of visual field and ocular surface parameters by clinical comparison after blepharoplasty for dermatochalasis

To evaluate the effect of upper eyelid blepharoplasty surgery on corneal topography, visual field, ocular surface, meibography, corneal biomechanics and dry eye parameters. This prospective study included a total 80 eyes of 40 patients. Following a detailed ophthalmological examination, standardized patient satisfaction questions were posed to patients before and after upper eyelid blepharoplasty surgery. Visual field test, non-invasive break up time (NIBUT), meibography, and corneal topography parameters were analyzed and evaluated. The mean (+) visible areas in the visual field were found to be 46.20±24.96 preoperatively, 56.73±21.98 at the 1st postoperative month and 65.96±18.5 at the 3rd month, which were statistically significant. NIBUT values preoperatively, at 1 month and at 3 months were 11.26±4.48, 11.16±4.5 and 10.14±4.0, respectively, which were statistically significant. Meibomian gland loss rates on meibography preoperatively and postoperatively at 1 and 3 months were found to be 30.24±8.3, 29.36±8.2 and 28.22±7.7 respectively and were statistically significant. With the scoring system after blepharoplasty, patients reported improvement in their symptoms. Upper eyelid blepharoplasty surgery is predicted to increase the quality of vision. It was observed that there was a functional and cosmetic improvement in the complaints of the patients after blepharoplasty. However, blepharoplasty may cause changes in eyelid dynamics and cause dry eye syndrome.

Retrospective Long-Term Results After Dellon's Nerve Decompression In The Lower Leg For Polyneuropathy

Patients affected by polyneuropathy often report pain, paraesthesia and numbness and are at risk of having an increased propensity to fall with the corresponding complications. In case of persistent symptoms after all conservative and medical treatment options have been exhausted, a nerve decompression in the lower leg as described by Dellon can lead to an improvement of the discomfort for many patients. This article presents our long-term results with Dellon's operation. In this retrospective study, we included 33 patients with diabetic or idiopathic polyneuropathy in whom we performed Dellon's nerve decompression in the lower leg in the years 2011-2013. In 29 out of the 33 patients, we investigated the level of pain (according to the numeric rating scale NRS 0-10), paraesthesia, numbness, Hoffman-Tinel sign, and Semmes-Weinstein monofilaments three months postoperatively. 88 months postoperatively (range 78-111 months), we were able to contact 20 of the 33 patients with a questionnaire asking about their present pain level (NRS 0-10), satisfaction with the postoperative result (NRS 0-10, 0=most satisfied, 10=not satisfied at all) and whether the patients would recommend the surgical procedure to their friends or family. 1. Significant pain reduction three months postoperatively, NRS 4.5 to 2.2, (p=0.000). 2. Significant reduction of paraesthesia three months postoperatively from 84.8 to 24.2% (p=0.000) 3. Significant reduction of numbness three months postoperatively from 97% to 39% (p=0.000). 4. Significant improvement of sensitivity three months postoperatively from 91% no sensitivity to 28% no sensitivity (p=0.000). 5. Significant improvement of Hoffmann-Tinel sign three months postoperatively from 76% to 13% (p=0.000). 88 months postoperatively, we saw a significant pain reduction from an average preoperative pain level of NRS 4.5 to a postoperative pain level of 2.7 (p=0.048). 88 months postoperatively, 65% of the patients would recommend the surgical procedure to their family and friends, and patient satisfaction was high (NRS 3,4). Our long-term results show that Dellon's nerve decompression in the lower extremities leads to a marked, lasting pain reduction and a functional improvement.

(063) Effect of Phosphodiesterase Type 4 Inhibitor on Erectile Function Recovery and Nerve Regeneration After Cavernous Nerve Injury in Rats

Abstract Introduction There is no consensus on the best treatment regimen for recovery of erectile function (EF) after radical prostatectomy (RP). Although many pharmacological interventions can improve EF in rats, there is still a lack of studies evaluating strategies that promote nerve regeneration of the cavernous nerve (CN). Phosphodiesterase type 4 inhibitors (PDE4Is), such as rolipram, have shown a neuroprotective effect after spinal cord injury in mice, facilitating functional recovery. It has also been suggested that the neuroprotective property of sildenafil is probably attributed to its effect on phosphodiesterase type 4. Objective Our aim was to evaluate the role of rolipram and its association with tadalafil in EF recovery and nerve regeneration after bilateral CN crush injury (BCNI) in rats. Methods Thirty-five male Wistar rats were randomly divided into four groups: (i) sham (no CN lesion); (ii) control (no treatment after BCNI); (iii) BCNI + tadalafil; (iv) BCNI + rolipram and (v) BCNI + tadalafil + rolipram. The initial laparotomy was performed and the CN were crushed with a hemostatic clamp. The animals in groups (iii) and (iv) received tadalafil (5mg/kg/d) or rolipram (1mg/kg/d) orally for 14 days, respectively. The animals in group (v) received tadalafil + rolipram at the same doses. Then, the animals were submitted to CN stimulation at frequencies 4, 8 and 16 Hz, with recording of mean arterial pressure (MAP) and intracavernosal pressure (ICP). EF was represented by the measurement of maximum ICP normalized to MAP (ICP/MAP ratio) and total normalized area under the curve (AUC) of ICP. The penises and CN of the animals were sent for structural evaluation with the immunohistochemical markers S100 and Ki-67. Results In the functional analysis, BCNI resulted in worse EF when compared to sham. This was observed when considering the maximum ICP/MAP and when analyzing normalized AUC of ICP for 4Hz and 8Hz. The different treatments were able to increase the ICP/MAP ratio after stimulation with 4Hz (p = 0.04) and 8Hz (p = 0.01). When considering normalized AUC of ICP, the different drugs (tadalafil, rolipram or tadalafil + rolipram) showed a significant improvement in EF in two of the three frequencies analyzed (4Hz and 8Hz) (figure 1). For 16hz, although it did not reach a statistical difference, a trend of improvement was observed after the different treatments (p = 0.08). With regard to immunohistochemical analysis, the tadalafil group had a higher expression of S100 in the dorsal penile nerve compared to the control group (p = 0.01). The rolipram group had a lower expression of Ki-67 in the CN compared to the control group (p = 0.03). Conclusions The combination of tadalafil and rolipram was associated with a functional improvement in EF in the experimental model with rats. The present study also suggests that rolipram may have a neuroprotective effect according to the structural evaluation of the CN. Disclosure No.

(289) Combined Therapy with Low-intensity Shockwave Therapy and Daily PDE5i Showed Better Pain Relieve and Sexual Function Improvement in Acute Phase of Peyronie Disease

Abstract Introduction To compare the efficacy and safety of daily use PDE5i and PDE5i combined with linear low-intensity shockwave therapy (Li-SWT) in the treatment of acute phase of Peyronie disease (PD). Objective 68 patients with acute PD within 6 month onset were collected. The patients were 26–56 years old with an average of 42.3 years. The patients were randomly divided into two groups, 35 of which were orally administered with 5 mg of tadalafil every night for 3 months; the other 33 received 4 times of Li-SWT with daily PDE5i. Li-SWT uses the Renova shock wave therapy device with an energy density of 0.09mJ/mm2, each time 3200 times in the penile plaque, 900 times in the left and right penile shaft, and once a week for 4 consecutive treatments as a cycle. All patients underwent ultrasound or MRI, penile bending angle measurement, improvement of subjective symptoms, and IIEF-5 scale before and after treatment. Methods 68 patients with acute PD within 6 month onset were collected. The patients were 26–56 years old with an average of 42.3 years. The patients were randomly divided into two groups, 35 of which were orally administered with 5 mg of tadalafil every night for 3 months; the other 33 received 4 times of Li-SWT with daily PDE5i. Li-SWT uses the Renova shock wave therapy device with an energy density of 0.09mJ/mm2, each time 3200 times in the penile plaque, 900 times in the left and right penile shaft, and once a week for 4 consecutive treatments as a cycle. All patients underwent ultrasound or MRI, penile bending angle measurement, improvement of subjective symptoms, and IIEF-5 scale before and after treatment. Results In the PDE5i group, the pain symptom relieve were improved in 80% patients (28 of 35 cases), while the combined group (PDE5i+Li-SWT) were improved in 90.9% patients (30 of 33 cases). The IIEF5 score in the PDE5i group improved from 13.8±7.9 to 19.5±8.1 and from 13.4±7.6 to 21.3±9.2 in the combined group, with both improvement between two groups. The plaque size were shrinkage 5 cases in PDE5i group and 12 cases in combined group, but penile curvature did not change significantly in both groups. In the PDE5i group, 5 patients had mild dizziness and back pain, while 3 patients had mild dizziness and back pain in combined group. There was no obvious adverse reaction observed for Li-SWT treatment. Conclusions Both the daily use PDE5i and the PDE5i combined with Li-SWT can improve the symptoms of acute PD patients, mainly to relieve pain and improve erectile function in some patients. The combined group had a better pain symptom relieve rate and more improvement for sexual function. The two methods can reduce PD plaque size in some cases, while both groups did not significantly change penile curvature. Both methods have good safety in the treatment of acute phase PD. Disclosure No.

The role of comprehensive rehabilitation in the care of degenerative cervical myelopathy

Study designRetrospective cohort study.ObjectiveTo find out if comprehensive rehabilitation itself can improve daily performance in persons with DCM.SettingThe spinal department of a rehabilitation hospital.MethodsData from 116 DCM inpatients who underwent comprehensive rehabilitation after spinal surgery were retrospectively analyzed. The definitions of the calculated outcome variables made possible analyses that distinguished the effect of rehabilitation from that of spinal surgery. Paired t-tests were used to compare admission with discharge outcomes and functional gains. Spearman’s correlations were used to assess relationships between performance gain during rehabilitation and between time from surgery to rehabilitation.ResultsThe Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI) increased during rehabilitation from 57 (24) to 78 (19) (p < 0.001). The Spinal Cord Independence Measure 3rd version (SCIM III) gain attributed to neurological improvement (dSCIM-IIIn) was 6.3 (9.2), and that attributed to rehabilitation (dSCIM-IIIr) 16 (18.5) (p < 0.001). dSCIM-IIIr showed a rather weak negative correlation with time from spinal surgery to rehabilitation (r = −0.42, p < 0.001).ConclusionsThe study showed, for the first time, that comprehensive rehabilitation can achieve considerable functional improvement for persons with DCM of any degree, beyond that of spinal surgery. Combined with previously published evidence, this indicates that comprehensive rehabilitation can be considered for persons with DCM of any functional degree, before surgery.