Therapeutics and Clinical Risk Management最新文献

The Bardet Biedl syndrome (BBS) is a rare inherited disorder considered a model of non-motile ciliopathy. It is in fact caused by mutations of genes encoding for proteins mainly localized to the base of the cilium. Clinical features of BBS patients are widely shared with patients suffering from other ciliopathies, especially autosomal recessive syndromic disorders; moreover, mutations in cilia-related genes can cause different clinical ciliopathy entities. Besides the best-known clinical features, as retinal degeneration, learning disabilities, polydactyly, obesity and renal defects, several additional clinical signs have been reported in BBS, expanding our understanding of the complexity of its clinical spectrum. The present review aims to describe the current knowledge of BBS i) pathophysiology, ii) clinical manifestations, highlighting both the most common and the less described features, iii) current and future perspective for treatment.

Purpose: Preseptal and pretarsal botulinum toxin injections are approved for treatment of hemifacial spasm and blepharospasm. However, the long-term data is limited. We compared the efficacy, safety, and costs between preseptal and pretarsal injection in hemifacial spasm and blepharospasm.

Patients and methods: The data were retrieved between 2011 and 2021. Consecutive hemifacial spasm and blepharospasm botulinum toxin patients were categorized as preseptal or pretarsal. Study outcomes were the difference in pre-and post-treatment modified Jankovic scale, self-reporting scales, time-related treatment, safety, and cost.

Results: Of 152 botulinum toxin-injected patients, 117 (77.0%) patients had hemifacial spasm and 35 (33.0%) patients had blepharospasm. Analysis included data pertinent to 1665 injections in hemifacial spasm (920 preseptal and 745 pretarsal) and 527 injections in blepharospasm (210 preseptal and 317 pretarsal). The difference between pre-and post-treatment modified Jankovic scale was lower in the preseptal group than in the pretarsal group in both hemifacial spasm and blepharospasm (1.5±0.8 vs 1.8±0.6, P-value <0.001 and 1.8±0.8 vs 3.1±0.9, P-value <0.001). There was no difference in duration of maximum response in hemifacial spasm between groups, while the blepharospasm with preseptal had a longer duration than blepharospasm with pretarsal. The preseptal injection was associated with more adverse events overall than the pretarsal (9.4% vs 5.2%, P-value <0.001). The total dose and cost per session in the preseptal group is lower for onabotulinum toxin but higher for abobotulinum toxin.

Conclusion: Pretarsal injections reduced symptom severity with fewer side effects. Further studies on the pharmacoeconomics of both techniques are required.

Articular cartilage repair is a sophisticated process that has is being recently investigated. There are several different approaches that are currently reported to promote cartilage repair, like cell-based therapies, biologics, and physical therapy. Cell-based therapies involve the using stem cells or chondrocytes, which make up cartilage, to promote the growth of new cartilage. Biologics, like growth factors, are also being applied to enhance cartilage repair. Physical therapy, like exercise and weight-bearing activities, can also be used to promote cartilage repair by inducing new cartilage growth and improving joint function. Additionally, surgical options like osteochondral autograft, autologous chondrocyte implantation, microfracture, and others are also reported for cartilage regeneration. In the current literature review, we aim to provide an up-to-date discussion about these approaches and discuss the current research status.

Background: The visualization of the glottis may be inadequate in morbidly obese patients when a standard Macintosh blade laryngoscope (MCL) is used. The Vie Scope^® (VS) is a novel type laryngoscope consisting of a straight, enclosed, illuminated tube that offers intubation via a bougie using the paraglossal technique. In this prospective, nonrandomized comparative study, we tested the research hypothesis that the VS may improve visualization of the glottic larynx in comparison to the MCL.

Materials and methods: After obtaining institutional ethics committee approval, 60 morbidly obese patients (BMI >40 kg/m²) undergoing elective non-head and neck surgery were included in the study. After induction of general anesthesia (GA), the glottic visualization was performed using the two laryngoscopes in succession, first MCL size 3 or 4 followed by the VS and was assessed using the modified Cormack-Lehane scale. Tracheal intubation was performed using the VS The first pass intubation success and the total success rate was recorded only for the VS Intubation time was not measured because of the paired study design.

Results and discussion: Mean demographic data included: age 41.9±8.2 years, height 171.2±10.2 cm, weight 129.9±21.6 kg, BMI 44.95±3.85 kg/m². Using MCL, Cormack-Lehane grade 1 was observed in 36 (60%) cases; grade 2 in 7/60 (11.6%); grade 3 in 13/60 (21.7%); and grade 4 in 4/60 (6.7%). Poor laryngeal views represented by grades 3 and 4 were observed in 28.4% of patients with the MCL. Grades obtained with the VS were all grade 1 (100%). The first attempt intubation success was in 58/60 (96.7%) with the VS. No complications were observed.

Conclusion: The Vie Scope^® laryngoscope, using the paraglossal technique of tracheal intubation, significantly improves visualization of the vocal cords in morbidly obese patients compared to the standard Macintosh laryngoscope.

Introduction: Psoriasis is a chronic, immune-mediated skin condition with significant detriments to physical/mental health. While systemic therapies are available for the treatment of moderate-to-severe psoriasis, patients can experience therapeutic failure, loss of efficacy, or medical contraindications that require other therapeutic options.

Objective: With the recent approval of deucravacitinib, a first-in-class TYK2 small molecule inhibitor administered orally for psoriasis patients, we reviewed data from randomized controlled trials (RCTs) to synthesize its clinical utility. To our knowledge, this is the first systematic review and meta-analysis of deucravacitinib comparing its clinical efficacy to placebo in psoriasis.

Methods: A literature search was conducted in PubMed (MEDLINE), Embase, and the Cochrane Central Register of Controlled Trials to identify RCTs studying deucravacitinib in human patients with moderate-to-severe psoriasis.

Results: One placebo-controlled Phase II RCT and two placebo-controlled/active-comparator Phase III RCTs were included for review. Patients (N=1953) treated with deucravacitinib 6 mg daily showed marked improvement in disease severity (Psoriasis Area and Severity Index (PASI), static Physician Global Assessment (sPGA) and quality-of-life outcomes compared to patients administered comparator (apremilast) and placebo. Clinical improvement given deucravacitinib was noted for scalp psoriasis but not fingernail psoriasis. Meta-analysis (deucravacitinib, n=888; placebo, n=466) comparing rates of clearance (sPGA 0/1) demonstrated superior efficacy of deucravacitinib compared to placebo (odds ratio, 12.87; 95% confidence interval, 8.97-18.48; χ²=4.08, I²=51%). Deucravacitinib was well-tolerated, with similar rate of occurrence and type of adverse events reported among patients treated with placebo or apremilast at Week 12-16. No cardiovascular events, serious infections, or lab abnormalities were noted.

Conclusion: Deucravacitinib possesses good efficacy, with no report of safety concerns associated with prior JAK inhibitors used for psoriasis. Meta-analysis demonstrated deucravacitinib's superiority compared to placebo, indicating its promising clinical utility. Further studies are needed to observe long-term safety and efficacy, and to compare deucravacitinib to existing treatments.

Inborn errors of thymic stromal cell development and function which are associated with congenital athymia result in life-threatening immunodeficiency with susceptibility to infections and autoimmunity. Athymic patients can be treated by thymus transplantation using cultured donor thymus tissue. Outcomes in patients treated at Duke University Medical Center and Great Ormond Street Hospital (GOSH) over the past three decades have shown that sufficient T-cell immunity can be recovered to clear and prevent infections, but post-treatment autoimmune manifestations are relatively common. Whilst thymus transplantation offers the chance of long-term survival, significant challenges remain to optimise the outcomes for the patients. In this review, we will discuss unmet needs and offer practical guidance based on the experience of the European Thymus Transplantation programme at GOSH. Newborn screening (NBS) for severe combined immunodeficiency (SCID) and routine use of next-generation sequencing (NGS) platforms have improved early recognition of congenital athymia and increasing numbers of patients are being referred for thymus transplantation. Nevertheless, there remain delays in diagnosis, in particular when the cause is genetically undefined, and treatment accessibility needs to be improved. The majority of athymic patients have syndromic features with acute and chronic complex health issues, requiring life-long multidisciplinary and multicentre collaboration to optimise their medical and social care. Comprehensive follow up after thymus transplantation including monitoring of immunological results, management of co-morbidities and patient and family quality-of-life experience, is vital to understanding long-term outcomes for this rare cohort of patients. Alongside translational research into improving strategies for thymus replacement therapy, patient-focused clinical research will facilitate the design of strategies to improve the overall care for athymic patients.

Pompe disease (PD) is a neuromuscular disorder caused by a deficiency of acid alpha-glucosidase (GAA) - a lysosomal enzyme responsible for hydrolyzing glycogen. GAA deficiency leads to accumulation of glycogen in lysosomes, causing cellular disruption. The severity of PD is directly related to the extent of GAA deficiency - if no or minimal GAA is produced, symptoms are severe and manifest in infancy, known as infantile onset PD (IOPD). If left untreated, infants with IOPD experience muscle hypotonia and cardio-respiratory failure leading to significant morbidity and mortality in the first year of life. In contrast, late-onset PD (LOPD) patients have more GAA activity and present later in life, but also have significant respiratory function decline. Despite FDA-approved enzyme replacement therapy, respiratory insufficiency remains a major cause of morbidity and mortality, emphasizing the importance of early detection and management of respiratory complications. These complications include impaired cough and airway clearance, respiratory muscle weakness, sleep-related breathing issues, and pulmonary infections. This review aims to provide an overview of the respiratory pathology, monitoring, and management of PD patients. In addition, we discuss the impact of novel approaches and therapies on respiratory function in PD.

Urinary incontinence is a common and debilitating problem in patients undergoing radical prostatectomy. Current methods developed to treat urinary incontinence include conservative treatments, such as lifestyle education, pelvic muscle floor training, pharmacotherapy, and surgical treatments, such as bulking agents use, artificial urinary sphincter implants, retrourethral transobturator slings, and adjustable male sling system. Pelvic floor muscle exercise is the most common management to improve the strength of striated muscles of the pelvic floor to try to recover the sphincter weakness. Antimuscarinic drugs, phosphodiesterase inhibitors, duloxetine, and a-adrenergic drugs have been proposed as medical treatments for urinary incontinence after radical prostatectomy. Development of new surgical techniques, new surgical tools and materials, such as male slings, has provided an improvement of outcomes after UI surgery. Such improvement is still ongoing, and the uptake of new devices might lead to even better outcomes after UI surgery.

Objective: This study aims to compare 1-month's efficacy and safety of single-session ethanol ablation and radiofrequency ablation for treating both purely cystic nodules and predominantly cystic thyroid nodules.

Materials and methods: This short-term retrospective study was approved by the Ethics Committee of the Institutional Review Board of Danang Family hospital, and written informed consent for procedures was obtained for all patients. Thirty-nine patients who presented with cystic thyroid nodules and met inclusion criteria were extracted from the computerized medical records. The internal fluid of cystic thyroid nodules was aspirated as much as possible. Ethanol ablation was performed using 18-gauge needles with 99.5% ethanol, and RFA used a cooled-electrode RFA system and 18-gauge internally cooled electrodes via the trans-isthmic approach, moving-shot technique. Nodule volume, therapeutic success rate, the largest diameter, thyroid function tests, and complications were evaluated and compared before and after treatment in each group.

Results: Among 39 patients, 17 patients were undergone EA (mean age of 47.35 years; the proportion of female of 76.5%; purely thyroid cyst percentage of 41.4%) and 22 patients were undergone RFA (mean age of 46.63 years; the proportion of female of 86.4%; purely thyroid cyst percentage of 54.5%). Both treatment techniques showed a significant reduction of the largest diameter and nodule volume (p<0.05) without complications. RFA reduced nodule volume and the largest nodule size greater than EA treatment at 1-month post-ablation (p<0.05). In addition, the therapeutic success rate in the RFA group was higher than in the EA group.

Conclusion: Both RFA and EA treatment with single-session confirm the efficacy and safety for cystic thyroid nodules at 1-month follow-up, RFA reduced greater in nodule volume and the largest nodule size than the EA treatment. Thus, the therapeutic success rate in the RFA group was higher than in the EA group.

Background: Whether hip revision with a metaphyseal-fixation femoral stem component can restore the bone mass of the proximal femur remains unclear. The aims of this study were to identify whether the bone mineral density (BMD) of the proximal femur increases following hip revision with a metaphyseal-fixation femoral stem and to identify the factors associated with BMD recovery.

Methods: This was a retrospective study involving 36 patients who underwent hip arthroplasty with a metaphyseal-diaphyseal fixation stem (standard length stem) and had indications for hip revision, which was performed with a proximal press-fit short-stem prosthesis for each patient. Dual-energy X-ray absorptiometry (DEXA) was used to obtain, evaluate, and compare the BMD at baseline and one year and two years postoperatively. The proximal femur was divided into several independent areas according to the Gruen zone (Gruen 1 to Gruen 7 from the greater trochanter counterclockwise to the lesser trochanter). Logistic regression analyses were used to assess potential factors significantly associated with an increase in BMD.

Results: An increased BMD was obviously identified in the proximal femur. Two years after the surgery, the BMD of the Gruen 1, Gruen 2, Gruen 6, and Gruen 7 areas had increased by 22.6%, 12.6%, 16.2% and 24.2%, respectively, relative to baseline. Three independent risk factors associated with bone mineral density recovery were identified: age (OR=1.100, 95% CI=1.005-1.203, P=0.038), osteoporosis (OR=14.921, 95% CI=1.223-182.101, P=0.034) and fair to poor hip function (OR=13.142, 95% CI=1.024-168.582, P=0.048).

Conclusion: This study confirms that metaphyseal-fixation stem hip revision can indeed help restore bone mass in the proximal femur, especially in the Gruen 1, Gruen 2, Gruen 6 and Gruen 7 zones. It was also found that advanced age, osteoporosis, and fair to poor hip joint function were three important risk factors affecting the recovery of proximal femur bone mass after surgery.

Trial registration: Retrospectively registered.