Additional Treatment Options Research Articles

Real-World Use and Outcomes of Therapies, Including Venetoclax-Based Treatments, after Discontinuation of a Covalent BTK Inhibitor in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Background Current treatment guidelines for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) support the use of covalent BTK inhibitor (cBTKi)-based regimens in the front-line setting. Optimal treatment sequencing following the discontinuation of cBTKi therapy, however, remains unknown. Venetoclax-based regimens, such as the combination of venetoclax plus rituximab, are commonly employed in the treatment of relapsed/refractory CLL/SLL; however, published clinical trial evidence is limited in the post-cBTKi setting due to the small numbers of patients treated with venetoclax-based therapies after cBTKi. This real-world study evaluated patient characteristics, treatment patterns, and clinical outcomes associated with immediate subsequent treatment, including the use of venetoclax-based treatment, after initial cBTKi discontinuation among US patients with CLL/SLL. Methods This descriptive, retrospective observational study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients with CLL/SLL aged 18 years or older were included who received at least one cBTKi (ibrutinib, zanubrutinib, or acalabrutinib) and at least one additional line of treatment immediately after their initial cBTKi treatment discontinuation from December 01, 2011, through March 31, 2022. Initial cBTKi treatment could be first line or second or later line of therapy. Patient characteristics and outcomes (time to treatment discontinuation or death [TTD-D], time to next treatment or death [TTNT-D], and overall survival [OS]) were reported. Kaplan Meier method was used for time-to-event outcomes, which were measured from the start of the post-cBTKi treatment. Results In this study, n=1,243 patients were analyzed with a median age of 72 years (range, 37-86) at post-cBTKi treatment initiation (Table 1). Most patients received their immediate post-cBTKi treatment in the second (61%) or third line (28%) setting. Twenty-three percent (n=288) of patients received venetoclax-containing regimens as the immediate post-cBTKi therapy, with 10% (n=120) who received venetoclax monotherapy (VenMono), 5% (n=63) venetoclax plus rituximab (VenR), and 8% (n=105) venetoclax plus other (e.g., chemoimmunotherapy, obinutuzumab). In the entire post-cBTKi cohort, the median TTD-D and TTNT-D were 6.5 (95% CI, 5.8-7.5) and 18.8 (95% CI, 16.1-21.7) months, respectively (Table 2). The median TTD-D and TTNT-D in the cohort that included all venetoclax-containing treatments were 12.9 (95% CI, 10.6-16.5) and 30.1 (95% CI, 23.8-39.4) months, respectively. For patients who received VenMono or VenR, the median TTD-D was 10.6 (95% CI, 7.5-16.0) months and median TTNT-D was 29.5 (95% CI, 18.6-39.4) months. Median OS was not reached for any of the cohorts investigated. Conclusions The findings of this study suggest that the outcomes observed in clinical trials of venetoclax-containing regimens, where patient populations may differ, may not be routinely extrapolated to patients who received a prior cBTKi. In addition, outcomes for patients treated in the post-cBTKi setting appear to be suboptimal overall. These data suggest the need for additional treatment options and sequencing data to determine the best treatment strategy following the discontinuation of initial cBTKi therapy.

The Co-Use of Stromal Vascular Fraction and Bone Marrow Concentrate for Tendon Healing.

The Achilles tendon is the most frequently injured tendon in the human body, despite being the strongest. Many conventional treatments including medication, surgical interventions, and physical therapy are available, however, the desired results are often not achieved. Stromal vascular fraction (SVF) and bone marrow concentrate (BMC) are two additional cellular treatment options. The purpose of this study is to evaluate the effect of SVF and BMC, used as a combination, for the treatment of Achilles tendon injuries. Five male New Zealand rabbits were used for each of the 6 study groups. A 3-mm of SVF and BMC were injected on the Achilles tendons at certain ratios. The histological results were classified by the Movin grading system for tendon healing. The collagen type-I and type-III structures in the tendons were examined by immunohistochemical evaluation. The expressions of tendon-specific genes were also examined by using the RT-PCR method to analyze tendon healing. Histological and immunohistochemical evaluation indicated that tendons receiving the SVF and BMAC mixture performed better than control and individual groups (p < 0.05). Moreover, RT-PCR evaluation showed that mixture-receiving groups were the closest similar to the uninjured group (p < 0.05). The combined use of BMC and SVF improved Achilles tendon healing when compared to the individual use of each mixture.

The impact of multimodal physiotherapy in an interdisciplinary setting for the management of women with persistent pelvic pain and pelvic floor tension myalgia

Purpose To determine the effectiveness of multimodal physiotherapy in an interdisciplinary setting for the treatment of women with persistent pelvic pain (PPP) who have concomitant pelvic floor tension myalgia (PFTM). Materials and methods Prospective cohort study with 2-year follow-up at an interdisciplinary tertiary referral centre for PPP and endometriosis. Thirty-four women with PPP of gynaecological origin >6 months duration and PFTM on examination underwent individualised physiotherapy. Outcome measures were pain, measured by Visual Analogue Scale (VAS) on a scale of 0–100, quality of life assessed by AQoL-6D score range 0.0–1.0 and sexual function measured by the Female Sexual Function Index (FSFI). Results Participants attended a median of 4 physiotherapy sessions (range 1–11) with the median treatment duration 7 weeks (range: 1–16 weeks). Results at 3 months demonstrated a significant decrease in VAS scores for dysmenorrhoea (72.5 vs. 52, p=.015), low back pain (55 vs. 47.5, p=.004), dyschezia (45 vs. 30.5, p=.031), abdominal pain (52 vs. 36.5, p=.049) and non-menstrual pain (53 vs. 41, p=.018) with a non-significant decrease in dyspareunia (57 vs. 50, p=.365). At 2 years, improvements in dysmenorrhoea persisted (72.5 vs. 60, p=.002) and dyspareunia was significantly improved (57 vs. 36, p=.033). For the 11/24 (46%) women who had no medical or surgical co-intervention throughout the study duration, quality of life score was improved at 2 years compared with baseline (0.72 vs. 0.84, p=.002). Conclusions Physiotherapy may improve certain pain outcomes in the short and long term. It offers an additional treatment option for women with PPP.

A Review of FLT3 Kinase Inhibitors in AML.

Acute myeloid leukemia (AML) is a highly aggressive illness distinguished by the accumulation of abnormal hematopoietic precursors in both the bone marrow and peripheral blood. The prevalence of FLT3 gene mutations is high and escalates the probability of relapse and mortality. The survival rates for AML patients, particularly those over 65, are low. FLT3 mutation screening at diagnosis is mandatory, and FLT3 inhibitors are crucial in treating AML patients with mutations. There are two categories of FLT3 mutations: FLT3-ITD located in the juxtamembrane domain and FLT3-TKD in the tyrosine kinase domain. FLT3-ITD is the most common type, affecting nearly a quarter of patients, whereas FLT3-TKD only affects 6-8% of patients. FLT3 inhibitors are now crucial in treating AML patients with FLT3 mutations. When dealing with FLT3-mutated AML, the recommended course of treatment typically involves chemotherapy and midostaurin, followed by allogeneic hematopoietic cell transplantation (HCT) to maximize the likelihood of success. Maintenance therapy can lower the risk of relapse, and gilteritinib is a better option than salvage chemotherapy for relapsed or refractory cases. Clinical trials for new or combined therapies are the most effective approach. This review discusses treatment options for patients with FLT3-mutated AML, including induction chemotherapy and options for relapsed or refractory disease. Additional treatment options may become available as more studies are conducted based on the patient's condition and susceptibility.

A - 172 STEP-Home Intervention Improves Inhibitory and Anger Control, Reintegration, and Neurobehavioral Symptoms in Post-9/11 Veterans with TBI and Other Common Comorbidities.

Post-9/11U.S. Veterans are clinically complex with multiple co-occurring health conditions contributing to morbidity/mortality and decreased quality of life. TBI diagnosis can worsen these outcomes. STEP-Home is a cognitive-behavioral transdiagnostic intervention for TBI and common comorbidities. This study determines if STEP-Home improves anger control, frontal system function, civilian readjustment, neurobehavioral symptoms, and work/life functioning in post-9/11 Veterans. TBI may influence Veterans' ability to learn core skills and, thus, impact response to treatment. Treatment outcomes for Veterans with and without TBI will be explored. 56 (39M/17F; mean age = 39.9) post-9/11 Veterans with high rates of psychiatric comorbidity, with and without TBI received 12weeks of the STEP-Home cognitive-behavioral intervention. Assessments at baseline, posttreatment (12weeks), and follow-up (12weeks posttreatment) included: State-Trait Anger Expression Inventory 2 (STAXI-2); Military to Civilian Questionnaire (M2CQ); Post-Deployment Readjustment Inventory (PDRI); Frontal Systems Behavioral Scale (FrSBe); Neurobehavioral Symptom Inventory (NSI); World Health Disability Scale (WHODAS); PTSD Checklist (PCL-5); Depression Anxiety and Stress Scale (DASS-21). STEP-Home significantly improved anger expression (STAXI-2 p = 0.0320), inhibitory control (FrSBe p = 0.0001), and reintegration status (MC2Q p = 0.0001; PDRI p = 0.0097) posttreatment. Similar improvements were seen in neurobehavioral symptoms, work/life functioning, PTSD, depression, and stress (p's < 0.01). Treatment gains were maintained at follow-up (p's < 0.001). Treatment response did not differ by TBI status. STEP-Home teaches Veterans cognitive-behavioral skills to improve anger and impulse control, executive functioning, reintegration, and work/life functioning. Treatment gains were comparable for Veterans with and without TBI. This is critical given TBI prevalence among post-9/11 Veterans and the need for additional palatable treatment options.

The Excretion of Cisplatin after Hyperthermic Intrathoracic Chemotherapy.

Hyperthermic intrathoracic chemotherapy (HITOC) is an additional intraoperative treatment option within the multimodality therapy of pleural malignancies. A chemotherapy perfusion with high-dose cisplatin is performed over a period of 60 min after surgical cytoreduction to improve local tumour control through the eradication of residual tumour cells. Although HITOC is increasingly used, there is only little scientific evidence about the necessary safety measures after HITOC. Therefore, the objective of this study was an analysis of cisplatin excretion via various body fluids after HITOC, with the aim of providing recommendations on occupational health and safety. Five patients undergoing HITOC were included. Before and after the HITOC, as well as during the following days, serum, urine, and bronchial secretion, as well as pleural effusion, were sampled. The platinum levels in the samples were measured using ICP-MS (inductively coupled plasma-mass spectrometry). Immediately after the HITOC, the mean levels of cisplatin increased dramatically in the serum (from 0.79 to 1349 µg/L), urine (from 3.48 to 10,528 µg/g creatinine), and bronchial secretion (from 0.11 to 156 µg/L). Thereafter, the cisplatin levels dropped to 133 µg/L in the serum and 994 µg/g creatinine in the urine within nine days after the HITOC. The AUC ratio shows 59% of the cisplatin being excreted via the urine after 48 h. The sampling of pleural effusion started 24 h after the HITOC, and the cisplatin levels decreased from 618 to 93 µg/L within nine days. Although the cisplatin levels in the body fluids of HITOC patients are much lower compared to patients receiving intravenous chemotherapy, a significant amount of cisplatin is excreted via these body fluids. Consequently, safety precautions must be implemented in the post-HITOC care of patients to avoid occupational exposure to cisplatin.

SAT085 Oral Glucagon-like Peptide-1 Receptor Agonist As Adjuvant Treatment In HNF1A-MODY

Abstract Disclosure: D.T. Broome: Grant Recipient; Self; NIH U54DK118612-04. Research Investigator; Self; Fractyl Laboratories, Novo Nordisk. Maturity-onset diabetes of the young (MODY) is an inherited form of monogenic diabetes caused by a mutation in a single gene. HNF1A-MODY is the most common treatment-requiring form of MODY with a reported frequency of 1.2%1. Early genetic diagnosis leads to more precise treatment, and sulfonylureas have been recognized as first-line treatment in patients with HNF1A-MODY. Although sulfonylurea treatment is often effective early in the disease course, patients often experience sulfonylurea treatment failure. As a result, there has been recent investigation into additional treatment options that are effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have previously been published for use in patients with HNF1A-MODY2,3, and recognized as a potential effective treatment in patients with HNF1A-MODY. Although GLP-1 RAs have been reported for use as injectable agents, there is currently no evidence reporting their effectiveness as oral medications. In this report, we present a novel case of use of oral semaglutide as adjuvant treatment to sulfonylurea in a patient with HNF1A-MODY. A 48-year-old female with a history of diabetes since age 22, later confirmed as HNF1A-MODY at age 45 (Heterozygous HNF1A mutation, c.608G&amp;gt;A (p.Arg203His), NM_000545.5), was glimepiride for 3 years and without micro- or macrovascular complications. She developed a 15-lb weight gain, and her HbA1c increased to 7% (HbA1c gradually increasing from 5.4% to 7.0% over 3 years) despite her taking glimepiride 4 mg twice daily prescribed by her primary care physician. Thereafter, her primary care physician prescribed oral semaglutide 3 mg once daily for 4 weeks, which was titrated to 7 mg once daily. After initiation of oral semaglutide, her glimepiride was reduced to 2 mg once daily, her HbA1c improved to 5.4%, and she lost 30 lbs over a 6-month timeframe. This is the first report demonstrating the benefits of oral GLP-1 RA treatment in a patient with HNF1A-MODY, and this clinical case provides further support of use GLP-1 RA use as adjuvant treatment to sulfonylurea in patients with HNF1A-MODY.

Use of Mobile Applications in Smoking, Alcohol and Substance Use Disorders

Currently, technology and mobile health applications are developing and being applied in different fields every day. Especially the use of mobile technology in many health fields offers various opportunities for the use of mobile applications in smoking, alcohol and substance use disorders, which is an important public mental health problem. The aim of this review study was to examine 16 mobile applications designed for the treatment and monitoring of smoking, alcohol and substance use. It was concluded that self-monitoring, notification and warning systems, location services, peer and expert support services were frequently used in the analyzed mobile applications. As a result of the studies, the use of mobile applications as a preventive intervention in the prevention of addiction and as an additional treatment option in addiction treatment is promising. However, this situation brings along various harms, risks and obstacles. This review of the relevant literature provides a critical update of mobile applications used in smoking, alcohol and substance use disorders. This review is expected to be an important guide for mental health professionals and mobile application designers working on addiction.

Clinical Trial and Real-World Outcomes of Patients With Metastatic NSCLC in the Post-Platinum–Based Chemotherapy Failure Setting

IntroductionA literature review was undertaken to identify clinical trials and real-world studies of patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy. MethodsThe EMBASE and MEDLINE databases were used to search for English-language studies published between September 28, 2017, and September 28, 2021. Studies were included in the review if they (1) were clinical trials or real-world analyses of one or more treatment regimens for patients with stage IV NSCLC who had progressed on or after treatment with platinum-based chemotherapy, (2) contained an end point including efficacy, effectiveness, or safety, and (3) included 45 or more patients. ResultsIn total, there were 15 publications (nine unique trials and three real-world studies) included. Sample size ranged from 49 to 1253 patients. At least one treatment arm in eight of the nine clinical trials reported an overall response rate of ≥15%. Median progression-free survival (PFS) and overall survival ranged from 1.9 to 5.2 months and 5.4 to 15.4 months in clinical trials and 4.4 to 6.8 months and 8.3 to 18.0 months in real-world studies, respectively. Within studies reporting median PFS, a median PFS of more than or equal to 3 months was reported in eight of 11 clinical trials and both real-world studies. Discontinuation due to adverse events ranged from 1.9% to 18% across all included studies. ConclusionsPatients with stage IV NSCLC had limited response and a high burden of adverse events during treatment after progression on platinum-containing chemotherapy. There remains a pressing unmet need for additional, effective, and tolerable treatment options in this setting.

Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms.

Objective: To review the safety, efficacy, and tolerability of fezolinetant for the treatment of vasomotor symptoms associated with menopause. Data Sources: A literature search was conducted through PubMed using the following search terms: fezolinetant, ES259564, SKYLIGHT, vasomotor symptoms, and menopause. Study Selection and Data Extraction: Selected articles included those which described clinical studies of the pharmacology, pharmacokinetics, efficacy, safety, or tolerability of fezolinetant. Data Synthesis: Fezolinetant works by inhibiting neurokinin B from binding to its receptor in the hypothalamus, thereby decreasing the occurrence of vasomotor symptoms. Clinical trials have demonstrated fezolinetant is superior to placebo in decreasing the frequency and severity of vasomotor symptoms. Common adverse effects associated with the use of fezolinetant include headache and gastrointestinal disturbances, as well as elevations in liver transaminase levels. Conclusions: Clinical practice guidelines for the treatment of vasomotor symptoms associated with menopause recommend hormone therapy as the most effective treatment option. Risks associated with hormone use may limit the use of this option in some patients. Neurokinin B inhibitors, like fezolinetant, target the physiologic cause of vasomotor symptoms. With the approval of fezolinetant, as well as elinzanetant which is currently in phase 3 clinical trials, providers and patients have additional nonhormonal treatment options for vasomotor symptoms associated with menopause.

Procalcitonin is elevated in severe malaria and is a promising biomarker of severe malaria and multi-organ dysfunction: A cross-sectional study and meta-analysis

BackgroundElevated procalcitonin (PCT) has been reported in bacterial infection and is positively associated with the severity of the disease. Patients with severe Plasmodium falciparum malaria also display higher procalcitonin levels compared to those with non-severe disease, indicating a possible role for bacterial infection in severe disease, however this observation remained variable in different study population. Furthermore, the significance of PCT in different clinical categories of severe malaria has not been evaluated so far. MethodsA total of 74 P. falciparum-infected subjects were enrolled in the study comprising of 55 cases complicated malaria [cerebral malaria- 14; non-cerebral severe malaria- 21; multi-organ dysfunction- 20] and 19 uncomplicated cases. Serum levels of PCT were quantified by fluorescence immunoassay. For meta-analysis, the literature search was performed in different databases, and all relevant articles were screened, and eligible reports were identified based on predefined inclusion and exclusion criteria. The meta-analysis was performed by comprehensive meta-analysis software V3 and MedCalc 20.218. ResultsPatients with severe P. falciparum malaria had significantly higher PCT levels compared to uncomplicated cases (p = 0.01). Analysis of PCT in different categories of patients with severe malaria revealed significantly elevated PCT in multi-organ dysfunctions compared to those with uncomplicated malaria (p = 0.004) and cerebral malaria (p = 0.05). Interestingly the receiver operating characteristics curve analysis showed procalcitonin as a promising biomarker for differentiating severe malaria (AUC: 0.697, p = 0.01) and multi-organ dysfunction (AUC: 0.704, p = 0.007) from uncomplicated malaria and other clinical categories of falciparum malaria, respectively. Furthermore, meta-analysis also revealed an elevated procalcitonin in severe malaria and it could be an important biomarker in the management of severe disease. ConclusionsPCT is elevated in P. falciparum-infected patients and could be a good biomarker for diagnosis of severe malaria and multi-organ dysfunction. It can help in the management of severe disease with additional treatment options.

Disease burden among patients with atopic dermatitis treated with systemic therapy for 4–12 months: results from the CorEvitas Atopic Dermatitis Registry

BackgroundReal-world data on the effectiveness of systemic therapy in atopic dermatitis (AD) are limited.MethodsAdult patients with AD in the CorEvitas AD registry (2020–2021) who received systemic therapies for 4–12 months prior to enrollment were included based on disease severity: body surface area (BSA) 0%–9% and BSA ≥10%. Demographics, clinical characteristics, and outcomes were assessed using descriptive statistics. Pairwise effect sizes (ES) were used to compare BSA groups.ResultsThe study included 308 patients (BSA 0%–9%: 246 [80%]; BSA ≥10%: 62 [20%]). Despite systemic therapy, both BSA groups reported the use of additional topical therapy and the presence of lesions at difficult locations. Moderate-to-severe AD (vIGA-AD®) was reported by 11% (BSA 0%–9%) and 66% (BSA ≥10%; ES = 0.56) of patients. Mean disease severity scores: total BSA (2% and 22%; ES = 3.59), EASI (1.1 and 11.1; ES = 2.60), and SCORAD (12.1 and 38.0; ES = 1.99). Mean scores for PROs: DLQI (3.7 and 7.5; ES = 0.75), and peak pruritus (2.2 and 4.5; ES = 0.81). Inadequate control of AD was seen in 27% and 53% of patients (ES = 0.23).ConclusionsPatients with AD experience a high disease burden despite systemic treatment for 4–12 months. This study provides potential evidence of suboptimal treatment and the need for additional effective treatment options for AD.

Advances in chemoablation in upper tract urothelial carcinoma: overview of indications and treatment patterns.

Localized upper tract urothelial carcinoma (UTUC) is a difficult disease for clinicians to treat, due to the multitude of oncological and patient factors to consider. Despite the challenges of diagnostic staging, endoscopic management, and disease recurrence, there is still a need for local therapeutic options that do not subject patients to the morbidities of radical nephroureterectomy (RNU). Intraluminal chemotherapies have allowed for improved oncological control in patients with low-grade disease receiving renal-sparing treatment approaches. This narrative review discusses the treatment modalities available for localized low-grade UTUC, with a focus on the current status of chemoablation. The OLYMPUS trial was a pivotal study that lead to the Food and Drug Administration (FDA) approval of UGN-101 (mitomycin-C) in April 2020 for the treatment of low-grade UTUC, and intraluminal chemotherapy is now a widely used modality for managing this disease. The trial reported a complete response (CR) rate of 59%, and an estimated treatment durability of 82% at 1 year. However, a concern was the reported 44% ureteral stricture rate using the retrograde approach. More research is currently underway to determine the ideal instillation method for intraluminal therapies (e.g., retrograde vs. antegrade). Lastly, we discuss upcoming treatment options. Newer novel agents like padeliporfin vascular targeted photodynamic (VTP) therapy (brand name TOOKAD) are currently being studied, which will in hope provide additional treatment options for UTUC patients.

Combined Laparoscopic Pyelolithotomy with RIRS in a Patient with Horseshoe Kidney Anomaly and Kidney Stone: A Case Report

Horseshoe Kidney is the most prevalent congenital kidney fusion anomaly, affecting 0.25 percent of the general population and occurring in 1 in 400 to 1600 births. Approximately forty percent of patients develop kidney stones due to anomalies. In our case, we aimed to perform combined laparoscopic pyelolithotomy with RIRS instead of PCNL in a patient with horseshoe anomaly. This procedure enabled us to detect the location of the mobile stone with RIRS and then successfully extract it with laparoscopic pyelolithotomy. Laparoscopic pyelolithotomy combined with RIRS is a reasonable additional treatment option for complicated stone surgery due to horseshoe kidney anomalies.

Diagnostic Approaches for Neuroendocrine Neoplasms of Unknown Primary (NEN-UPs) and Their Prognostic Relevance-A Retrospective, Long-Term Single-Center Experience.

Neuroendocrine neoplasms (NENs) represent a rare and heterogenous group of tumors with predominantly gastroenteropancreatic or pulmonary origin. Despite numerous diagnostic efforts, the primary tumor site remains unknown in up to 20% of the patients diagnosed with NEN. In this subgroup of NEN patients, a standard diagnostic algorithm has not yet been integrated into clinical routine. Of note, an undetermined primary tumor site in NENs is associated with an impaired clinical outcome by at least "formally" limiting treatment options exclusively approved for NENs of a certain histological origin. In this retrospective study, a patient cohort of 113 patients initially diagnosed with NEN of unknown primary (NEN-UP) was analyzed. In 13 patients (11.5%) a primary tumor site could be identified subsequently, amongst others, by performing somatostatin receptor (SSTR)-PET-based imaging, which was irrespective of the initial clinical or demographic features. Diagnostic work-up and therapeutic regimens did not differ significantly between patients with an identified or unidentified primary tumor site; only a detailed immunohistochemical assessment providing additional information on the tumor origin proved to be significantly associated with the detection of a primary tumor site. Our study revealed that a profound diagnostic work-up, particularly including SSTR-PET-based imaging, leads to additional treatment options, finally resulting in significantly improved clinical outcomes for patients with NEN-UPs.

Challenges and Future Trends in the Treatment of Psoriasis.

Psoriasis is a chronic inflammatory skin disorder, and current treatments include topical therapies, phototherapy, systemic immune modulators, and biologics, aiming to alleviate symptoms and improve quality of life. However, challenges persist, such as adverse effects, treatment resistance, high costs, and variability in response among individuals. The future of psoriasis treatment shows promising emerging trends. New biologic agents targeting novel pathways, such as interleukin 23 inhibitors like mirikizumab, offer enhanced efficacy. Small molecule inhibitors like RORγt inhibitors and ROCK2 inhibitors provide additional treatment options. Combination therapies, including biologics with methotrexate, may improve treatment response. Advancements in topical treatments utilizing microneedles and nanoparticle-based carriers can enhance drug delivery and improve therapeutic outcomes. Biomarkers and multi-omics technologies hold potential for personalized treatment approaches, thus aiding in diagnosis, predicting treatment response, and guiding therapeutic decisions. Collaboration among researchers, clinicians, and industry stakeholders is crucial to translating these scientific breakthroughs into clinical practice. By addressing current challenges and exploring these promising trends, we can optimize psoriasis management and improve the lives of those affected by this chronic condition.

Neuroendovascular Surgery Applications in Craniocervical Trauma.

Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions.

Identification of the HNSC88 Molecular Signature for Predicting Subtypes of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSC) exhibits genetic heterogeneity in etiologies, tumor sites, and biological processes, which significantly impact therapeutic strategies and prognosis. While the influence of human papillomavirus on clinical outcomes is established, the molecular subtypes determining additional treatment options for HNSC remain unclear and inconsistent. This study aims to identify distinct HNSC molecular subtypes to enhance diagnosis and prognosis accuracy. In this study, we collected three HNSC microarrays (n = 306) from the Gene Expression Omnibus (GEO), and HNSC RNA-Seq data (n = 566) from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) and validate our results. Two scoring methods, representative score (RS) and perturbative score (PS), were developed for DEGs to summarize their possible activation functions and influence in tumorigenesis. Based on the RS and PS scoring, we selected candidate genes to cluster TCGA samples for the identification of molecular subtypes in HNSC. We have identified 289 up-regulated DEGs and selected 88 genes (called HNSC88) using the RS and PS scoring methods. Based on HNSC88 and TCGA samples, we determined three HNSC subtypes, including one HPV-associated subtype, and two HPV-negative subtypes. One of the HPV-negative subtypes showed a relationship to smoking behavior, while the other exhibited high expression in tumor immune response. The Kaplan-Meier method was used to compare overall survival among the three subtypes. The HPV-associated subtype showed a better prognosis compared to the other two HPV-negative subtypes (log rank, p = 0.0092 and 0.0001; hazard ratio, 1.36 and 1.39). Additionally, within the HPV-negative group, the smoking-related subgroup exhibited worse prognosis compared to the subgroup with high expression in immune response (log rank, p = 0.039; hazard ratio, 1.53). The HNSC88 not only enables the identification of HPV-associated subtypes, but also proposes two potential HPV-negative subtypes with distinct prognoses and molecular signatures. This study provides valuable strategies for summarizing the roles and influences of genes in tumorigenesis for identifying molecular signatures and subtypes of HNSC.

Evidence-based guideline: unexplained infertility†.

Evidence-based guideline: unexplained infertility†.

Prescribing Patterns of Oral Antibiotics and Isotretinoin for Acne in a Colorado Hospital System: Retrospective Cohort Study.

Guidelines established by the American Academy of Dermatology recommend oral antibiotics as first-line therapy for mild, moderate, and severe acne. However, it is recommended to minimize the duration of oral antibiotic use, and there is increasing support for other systemic agents for acne. We sought to characterize the use of oral antibiotics and isotretinoin for the treatment of acne in the pediatric and young adult population aged 10 through 20 years and the adult population aged 21 to 45 years from 2011 to 2019. We conducted a retrospective, observational cohort study using electronic data from the enterprise data warehouse of the University of Colorado Anschutz Medical Campus and its affiliates, with data in the format of the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) common data model. Categorical values (sex, race, and ethnicity) were compared using chi-square tests, and continuous variables (age) were compared using 2-tailed t tests. Our cohort of 15,704 patients was composed of mostly White (12,776/15,704, 81.4%), non-Hispanic or Latino (13,307/15,704, 84.7%), and female (11,093/15,704, 70.6%) patients. Among the 4605 male patients in the eligible cohort, 1810 (39%) received an oral antibiotic treatment, in comparison to 3109 (28%) of the 11,093 eligible women (P<.001). Among the 4605 men who were eligible for treatment with isotretinoin in this population, 988 (21.5%) received a course of isotretinoin, compared to only 10.4% (1159/11,093) eligible women (P<.001). Male patients were 1.67 times more likely to have received an antibiotic prescription(odds ratio [OR] 1.67, 95% CI 1.55-1.79) and over twice as likely to have received an isotretinoin prescription (OR 2.34, 95% CI 2.13-2.57) than female patients. Minocycline was the most frequently prescribed antibiotic for the treatment of acne in this study cohort. From 2015 to 2019, there was no significant change in the number of antibiotic prescriptions over time. Men were significantly more likely to receive both oral antibiotics and isotretinoin than female patients. Multiple factors could be contributing to this discrepancy, including the burden of iPLEDGE, additional systemic treatment options for female patients, and the difference in acne severity across sexes. We could not determine the difference in severity of acne between male and female patients in our cohort, and further research is needed to ascertain the variation across sexes.