First-line Treatment Option Research Articles

Elucidating the Signaling Pathways Involved in Erectile Dysfunction

Background: Erectile Dysfunction (ED) is a common sexual disorder among men aged 20 years and over. It is predominantly characterized by alterations in the key physiological pathways regulating erectile function, such as nitric oxide and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK). Beyond these pathways, multiple molecular signaling networks are involved in ED pathogenesis. Objective: This review aims todescribe the major signal transduction pathways that impact erectile function and contribute to the introduction of the pathogenesis of ED. Methods: A literature review of ED was performed from 2000 to 2023 using PubMed, Scopus, and Embase. “ED” and “related signaling pathway”, “molecular mechanisms” terms were used. Results: Further basic and clinical studies are required to define the underlying molecular mechanisms of ED. The signaling pathways that were not affected by phosphodiesterase type 5 inhibitors (PDE5i) may be the reason for the reduced efficacy of this first-line treatment option in a variety of conditions. Conclusion: There is still a need for a deeper description of the molecular mechanisms in terms of fibrosis, angiogenesis, apoptosis, inflammation, oxidative stress, autophagy, and hypoxia to identify new possible targets underlying the pathogenesis of ED. This comprehensive review expounds on the principal signaling pathways, offering valuable insights that may catalyze the development of innovative and enhanced therapies for managing ED.

SSA-ZP on Scalp Seborrheic Dermatitis: Regulating Sebum Levels and Scalp Barrier.

The occurrence of scalp seborrheic dermatitis (SD) is closely related to the production of sebum and scalp barrier function. Supramolecular salicylic acid has the keratolytic and anti-inflammatory properties, and zinc pyrithione is an antifungal drug delivered as a microparticle to skin epithelia. This study aimed to assess the efficacy and safety of 2% supramolecular salicylic acid (SSA) combined with 0.8% zinc pyrithione conditioner (SSA-ZP) in treating scalp SD focusing on key outcome measures including sebum levels and scalp barrier function. Five patients with mild to moderate scalp SD were included in the 2-week self-controlled prospective study, receiving daily SSA-ZP treatment. Evaluation on days 0, 7, and 14 included dermoscopy, the adherent scalp flaking scale (ASFS), sebum level, transepidermal water loss (TEWL), pH, and stratum corneum hydration. We also performed the fungal count across specific scalp regions, such as the left and right sides of the forehead, the top of the head, and the occiput. Five patients with mild to moderate scalp SD participated in this study. After 2 weeks of SSA-ZP treatment, significant reductions in ASFS scores, sebum levels, and fungal count were observed, alongside improvements in TEWL and pH values across multiple scalp regions. Moreover, there was no difference in the hydration of stratum corneum. SSA-ZP demonstrated efficacy in treating scalp SD without adverse effects, suggesting its potential as a first-line treatment option. Further research with larger sample sizes and longer follow-up periods is warranted to validate these findings.

The predictive value of left atrial functional parameters for recurrence of atrial fibrillation after catheter ablation in patients

Abstract Background Catheter ablation (CA) is a first-line treatment option for patients with symptomatic or drug-refractory atrial fibrillation (AF), yet the recurrence rate of AF post-CA remains considerably high. Studies have reported that left atrial (LA) functional parameters can serve as predictive factors for AF recurrence, however, the results remains controversial. Purpose This study aims to investigate the predictive value of LA functional parameters for AF recurrence following CA in patients. Methods We prospectively enrolled patients with AF who underwent CA for the first time from June 2022 to May 2023 and met the inclusion criteria at our institution. All patients underwent pre-ablation evaluation of LA structure and function, including LA diameter (LAD), LA maximum volume (LAVmax), LA minimum volume (LAVmin), LA pre-systolic volume (LAVpre), LA reservoir strain (LASr), LA strain conduit (LAScd), LA contraction strain (LASct), and LA ejection fraction (LAEF) using three-dimensional speckle tracking echocardiography. AF recurrence was defined as atrial tachycardia occurring 3 months after ablation and lasting longer than 30s. Patients were followed up for 9 months post-CA , and the primary end point was any atrial tachycardia occurring at 3 months after ablation. Results A total of 85 patients with AF were ultimately included in this study, with an average age of 68.9±11.0 years, 54.2% of whom were male. During the 9-month follow-up, 30 patients (35.29%) experienced recurrence postoperatively, while 55 patients (64.71%) still maintained sinus rhythm. Compared with the AF non-recurrence group, the AF recurrence group had significantly increased LAD (46.4±5.5mm vs. 42.3±4.5mm, p<0.05), LAVmax (80.7±21.3mL vs. 67.1±22.0mL, p<0.05), LAVmin (63.8±18.0mL vs. 42.8±16.9mL, p<0.05) and LAVpre (72.4±19.4mL vs. 53.9±16.8mL, p<0.05). Meanwhile, in AF recurrence group, LAEF (21.7±6.8% vs. 37.5±8.0%, p<0.05), LASr (5.1±3.1% vs. 12.0±5.4%, p<0.05), LAScd (-4.0±3.6% vs. -7.3±5.7%, p<0.05), and LASct (-1.0±3.8% vs. -3.3±4.9%, p<0.05) were significantly decreased. Multivariate logistic regression analysis revealed that LASr (OR=0.640, 95%CI 0.425-0.964, p<0.05) and LAEF (OR=0.816, 95%CI 0.694-0.960, p<0.05) were independent risk factors for predicting AF recurrence. ROC curve analysis showed that both LAEF (AUC=0.935, 95%CI 0.871-0.999) and LASr (AUC=0.903, 95%CI 0.833-0.973) possess high predictive values. Furthermore, the combined model of LAEF and LASr (AUC=0.954, 95%CI 0.905-1.000) had a greater predictive value than any one of the two indicators (p<0.05). Conclusion Taken together, these findings indicate that LAEF and LASr are independent predictors of AF recurrence following CA in patients with AF. Combination of the two indicators can more accurately assess the risk of recurrence in AF patients post-CA.

Beyond Painkillers: A Meta-Analysis of Non-Pharmacological Approaches for Managing Dysmenorrhea Symptoms

Dysmenorrhea, commonly known as painful menstruation, is a highly prevalent gynecological condition affecting millions of women globally. While pharmacological interventions offer temporary relief, they often come with undesirable side effects. Non-pharmacological approaches present a potentially safer and more sustainable alternative for managing dysmenorrhea symptoms. A comprehensive search of electronic databases, including PubMed, Scopus, and Web of Science, was conducted to identify randomized controlled trials (RCTs) published between 2014 and 2024 that investigated the effectiveness of non-pharmacological interventions for dysmenorrhea. The primary outcome was pain intensity reduction, while secondary outcomes included quality of life, absenteeism, and medication use. Data were pooled using a random-effects model, and standardized mean differences (SMDs) were calculated. Six RCTs met the inclusion criteria, encompassing a total of 600 participants. The non-pharmacological interventions evaluated included aerobic exercise, yoga, acupuncture, transcutaneous electrical nerve stimulation (TENS), heat therapy, and relaxation techniques. The pooled analysis revealed significant reductions in pain intensity across all interventions compared to control groups (SMD = -2.00, 95% CI: -2.39 to -1.61, p < 0.001). Aerobic exercise and yoga demonstrated the largest effect sizes (SMD = -2.5 and -2.5, respectively). Significant improvements were also observed in quality of life, absenteeism, and medication use. Non-pharmacological approaches, particularly aerobic exercise and yoga, are effective in managing dysmenorrhea symptoms. These findings strongly support the integration of non-pharmacological interventions into clinical practice as a first-line or adjunctive treatment option for dysmenorrhea.

The development and testing of a single-arm feasibility and acceptability study of a whole foods diet intervention for adults with prediabetes and their offspring

BackgroundDiet is considered a first-line treatment option for prediabetes, a condition that affects 96 million United States (U.S.) adults. Diet patterns that prioritize whole foods (e.g., Mediterranean) are currently recommended to treat prediabetes. However, no studies have tested whether a U.S.-style diet pattern that prioritizes whole foods can be used to treat prediabetes. The purpose of this study was to assess the feasibility and acceptability of a whole foods diet for adults with prediabetes and their offspring prior to conducting a larger clinical trial.MethodsA 2-week single-arm pre-post experimental controlled-feeding intervention of a 2020–2025 Dietary Guidelines for Americans adapted whole foods diet (e.g., primarily focused on foods that have undergone limited processing or refinement) was conducted in adults (25–59 years) with prediabetes and their biological offspring (6–17 years). Families received 2 weeks of menus and grocery delivery and weekly counseling by a registered dietitian. Families were invited to attend an optional focus group session. Feasibility was based on having a ≥ 50% family completion rate with ≥ 80% completion of study outcomes. Measures included adult–child anthropometrics (weight [kg], body mass index [BMI] including BMI% and Z-scores for offspring, waist circumference [cm]) and child diet quality estimated using the 2015 Healthy Eating Index (HEI) from a single random food record. Wilcoxon signed rank was used to compare differences between baseline and 2-week anthropometrics measures and offspring total HEI scores. Qualitative data were analyzed using thematic analysis to understand factors attributed to diet adherence and acceptability.ResultsEight families enrolled (n = 8 adults, n = 12 offspring), with 7 families completing the study (12% attrition) and completing 100% of study outcome measures. Adults experienced a median weight loss of − 1.0 kg from baseline to 2 weeks (79.5 kg to 78.5 kg). Offspring had a 24-point increase in total 2015 HEI scores (median difference 50 to 74). Focus group participants (n = 4 adults) reported being satisfied with the program and expressed a willingness to continue the diet despite identified barriers.ConclusionsA whole foods diet that provides dietary support was found to be feasible and acceptable for families at risk for T2D. Future studies are needed to test the effects of the diet on prediabetes outcomes, diet quality, and diet adherence in adults and families.Trial registrationNCT05483972 at ClinicalTrials.gov. Registered July 25, 2022. https://clinicaltrials.gov/study/NCT05483972?cond=prediabetes&term=whole%20foods%20&rank=1

Prevalence of urinary incontinence in postpartum women and physiotherapy interventions applied: An integrative review.

This integrative review identified studies that reported the prevalence of physiotherapeutic interventions for urinary incontinence among postpartum women. This is an integrative literature review study. We used the integrative literature review framework proposed by Whittemore and Knafl to search for relevant literature. The search strategy for electronic databases was developed from the research question and definitions of key concepts, assisted by the librarian. Databases that were searched include Google Scholar, Medline (PubMed), CINAHL, and the Joanna Briggs Institute databases. Both qualitative and quantitative studies that met the inclusion criteria were included. We used the CASP tool to assess the quality of selected papers. The included articles were thematically analyzed. Thirty-six papers met the inclusion criteria for the review. Six themes emerged from the analysis: prevalence of postpartum UI; risk factors for postpartum UI; antenatal pelvic floor muscle training; conservative treatment and quality of life; experiences of postpartum women with UI; and possible coping strategies adopted by women. Most of the articles were quantitative studies (80.5%); 16.6% were qualitative and 2.7% adopted mixed methods. Urinary incontinence is common in postpartum women. Antenatal pelvic floor muscle training is protective against postpartum UI and should be the first-line treatment option.

Antibiotic Susceptibility among Infective Endocarditis Population: Syndromic Antibiogram Evaluation at Indonesian National Cardiovascular Center

Infective Endocarditis (IE) is a life-threatening disease with a high mortality rate (25%). Laboratory approaches to support the diagnosis of IE especially blood and/or cardiac vegetation culture, are crucial for providing definitive therapy. However, negative culture is frequently observed, therefore empirical use of antibiotics seems unavoidable and may lead to increasing antimicrobial resistance. This study aims to observe the prevalence of antibiotic susceptibility among the IE population using the WISCA approach. This retrospective study observed medical record data of all inpatients diagnosed with IE according to ICD-10 at Cardiovascular Center Harapan Kita Hospital (NCCHK) between January 2018 and December 2022. Patient data were combined with bacterial identification and antibiotic susceptibility test data from the laboratory information system, and evaluated based on period (year). A total of 67,858 inpatients and 1.1% (n=772) were diagnosed with IE. Successful culture growth (blood and/or cardiac vegetation specimen) was between 36.8% and 70% annually. Streptococcus viridans group (82/237, 34.6%) and Coagulase-negative Staphylococci (57/237, 24.1%) were dominantly observed among the IE population. Low susceptibility among Penicillin (34.3%) towards Gram-positive bacteria, as first-line treatment option in IE. Meanwhile, high susceptibility range was observed in Ceftriaxone (95.7%), Gentamicin (80.4%), Rifampicin (84.4%), and Vancomycin (98.7%) as second-line treatment in IE. Despite the low prevalence, the occurrence of antimicrobial resistance in IE has become a priority concern. Continuing the syndromic antibiogram is mandatory to assist the trend of empirical antibiotic usage and refine the established local treatment guidelines.

Pemetrexed and platinum with or without pembrolizumab for advanced non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis.

This meta-analysis aimed to evaluate the efficacy and safety of combining pemetrexed and platinum with or without pembrolizumab for the treatment of advanced non-small-cell lung cancer (NSCLC). A systematic search of PubMed, Embase, Cochrane Library, and Web Of Science databases was conducted to identify studies comparing pemetrexed and platinum with or without pembrolizumab in advanced NSCLC. Raw data were extracted from eligible studies to calculate Hazard Ratios (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), as well as rates of adverse events of all grades and those of Grade 3 or higher. Eight studies with 1639 patients occurred advanced NSCLC included. The group receiving pembrolizumab in combination with pemetrexed and platinum showed significant benefits in terms of OS (HR 0.63; 95% CI 0.54-0.73; p < 0.00001) and PFS (HR:0.64; 95% CI 0.48-0.85; p = 0.002) compared to the group receiving pemetrexed and platinum alone. However, this benefit was accompanied by a higher incidence of Grade 3 or higher adverse events (OR: 1.55; 95% CI 1.24-1.95; p = 0.0001). The combination of pemetrexed and platinum with pembrolizumab is recommended as a first-line treatment option for advanced NSCLC due to its significant efficacy benefits. However, the increased risk of Grade 3 or higher adverse events suggests the need for careful consideration and assessment when considering this regimen for second-line or subsequent therapy.

Targeting Hypoxia and Autophagy Inhibition via Delivering Sonodynamic Nanoparticles With HIF-2α Inhibitor for Enhancing Immunotherapy in Renal Cell Carcinoma.

Immune checkpoint blockers (ICBs) therapy stands as the first-line treatment option for advanced renal cell carcinoma (RCC). However, its effectiveness is hindered by the immunosuppressive tumor microenvironment (TME). Sonodynamic therapy (SDT) generates tumor cell fragments that can prime the host's antitumor immunity. Nevertheless, the hypoxic microenvironment and upregulated autophagy following SDT often lead to cancer cell resistance. In response to these challenges, a hypoxia-responsive polymer (Poly(4,4'-azobisbenzenemethanol-PMDA)-mPEG5k, P-APm) encapsulating both a HIF-2α inhibitor (belzutifan) and the ultrasonic sensitize (Chlorin e6, Ce6) is designed, to create the nanoparticle APm/Ce6/HIF. APm/Ce6/HIF combined with ultrasound (US) significantly suppresses tumor growth and activates antitumor immunity in vivo. Moreover, this treatment effectively transforms the immunosuppressive microenvironment from "immune-cold" to "immune-hot", thereby enhancing the response to ICBs therapy. The findings indicate that APm/Ce6/HIF offers a synergistic approach combining targeted therapy with immunotherapy, providing new possibilities for treating RCC.

Asia-Pacific consensus recommendations on the management of generalized pustular psoriasis.

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life-threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia-Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts' collective expertise. The experts agreed that GPP is a rare, severe, and potentially life-threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient's unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first-line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision-making processes.

Could macrocytosis predict survival In advanced breast cancer patients that were treated with CDK 4–6 inhibitors?

IntroductionCyclin Dependent Kinase (CDK) 4–6 inhibitors are the recommended first-line treatment option for hormone-positive metastatic breast cancer (MBC). They show their effects by causing cell cycle arrest in G1-S phase. Neutropenia is the most common haematological side effect. In the literature, data on the association between CDK 4–6 inhibitors and macrocytosis are limited. We aimed to investigate the effect of macrocytosis on survival. MethodsWe retrospectively analysed 133 patients with de novo hormone positive MBC using CDK 4–6 inhibitors in first line treatment. Mean Corpuscular Volume (MCV) > 100 was considered macrocytosis and patients were divided into two groups; MCV<100 and MCV >100. The association of macrocytosis with clinicopathological features, Progression Free Survival (PFS) and Overall Survival (OS) were evaluated. Results42 patients were receiving palbociclib and 81 patients were receiving ribociclib. Median OS was determined as 33 months and median PFS was determined as 22 months. Macrocytosis ever rate was 45.8 % during follow-up. Macrocytosis was observed in 4.2 % of the patients in the first month, 16.7 % in the third month, 41.6 % in the sixth month and 42.2 % in the twelfth month. ER receptor level, ki-67, macrocytosis at 6–12 months and macrocytosis-ever which were found to affect OS as a result of univariate Cox regression analysis, were evaluated with multivariate Cox regression models and it was observed that they had significant effect on PFS and OS. ConclusionMacrocytosis may be a useful biomarker for the prediction of PFS and OS in MBC patients receiving CDK 4–6 inhibitors.

Floppy iris. How is floppy iris syndrome managed? What do urologists and ophthalmologists say?

This study focuses on the effect of chronic treatment on the eye, regarding the so-called Intraoperative Floppy Iris Syndrome (IFIS) or Floppy Iris Syndrome, which can occur during cataract surgery. The study aimed to establish the influence of tamsulosin, used in benign prostatic hyperplasia (BPH) treatment on the iris, during cataract surgery, considering the increased incidence of both conditions in older age. This study included one hundred male patients, operated on for cataracts at the Ofta Total Clinic and Dr. Stănilă Medical Centre, in Sibiu, out of 601 patients operated on for cataracts between February and October 2022. Of the 100 patients, 24 used medication for BPH. 5 patients used prostamol, a phytotherapeutic preparation, which is an extract from Serenoarepens, and the remaining 19 used tamsulosin, which is an alpha-blocker, most commonly used in the treatment of BPH, considered the first-line treatment option. In 15 patients, we intraoperatively managed, a medium mydriasis through pharmacological dilation, including intracameral administration of phenocaine and mechanical dilation or stripping. In 4 patients it was necessary to apply iris dilators. Due to the small pupil in 2 patients, we caught the iris in the phacoemulsification probe, and a small, incomplete iris coloboma was formed. Sometimes, there was a turnover of Descemet in 4 patients. The pupil remained semi-dilated and slightly areflective in the patients to whom we applied iris hooks. The patients' visual acuity was satisfactory, between 0.9 and 0.6. The topic gives rise to many discussions. It seems that stopping the administration of tamsulosin for a short time does not help the occurrence of IFIS, because the iris lesions seem irreversible. Patients at risk of developing cataracts should be evaluated and possibly referred to an ophthalmologist to determine surgery before starting treatment for BPH and to competently assess the administration of this medication. Collaboration between urologists and ophthalmologists is required for patients prone to the appearance of cataracts since both conditions are frequently encountered in elderly patients.

A Holistic View on Erectile Dysfunction: South African Medicinal Plants as Sustainable Alternative Therapies

Erectile dysfunction is a common problem affecting men worldwide, especially as they age. This condition is characterized by the inability to achieve or maintain an erection firm enough for sexual intercourse and may result from various factors, including vascular, neurogenic, hormonal, and psychological. Common first-line treatment options for the disease have relied on phosphodiesterase-5 inhibitors such as sildenafil (Viagra), which are costly, inaccessible, and sometimes result in adverse health effects. Consequently, there has been increasing interest in exploring medicinal plants as alternative remedies because of their easy access and affordability. In South Africa, 75 plant species with properties that affect testosterone levels, luteinizing hormone, and follicle-stimulating hormone are used as aphrodisiacs. Some plant extracts can increase blood testosterone concentrations and stimulate penile erection by maintaining nitric oxide levels. This paper presents current information about the possible utilization of South African medicinal plants as viable and readily available therapeutic alternatives for managing erectile dysfunction. In addition, it discusses in detail the various mechanisms of action of medicinal plants in managing the disease. The information on the efficacy of African medicinal plants in managing erectile dysfunction provided in this review will help increase awareness of the sustainable use of natural products. It may serve as a basis for including indigenous herbal remedies in the guidelines for erectile dysfunction management as potential treatment options in Africa.

Choroidal Changes and Choroidal Neovascularization in Pathological Myopia

Among the complications of pathological myopia, myopic macular neovascularization (mMNV) is one of the most vision-threatening complications. Despite significant advances in understanding the epidemiology, pathogenesis, and natural history of the disease, there is no standard definition of mMNV. Although the sensitivity of mMNV diagnosis increases to 97% with the combined use of fundus fluorescein angiography and optical coherence tomography, multimodal imaging is valuable in differential diagnosis. Intravitreal anti-vascular endothelial growth factor therapy has become the standard and first-line treatment option for mMNV. Continued monitoring of patients is required to assess any progression or recurrence.

Preparation and Formulation of a New Therapeutic Supplement by the Combination of Dendritic Cells and IPI-549 (Eganelisib) for the Treatment of Breast Cancer in BALB/c Mice

: Dendritic cell-based cancer immunotherapy is considered an innovative and promising approach aimed at enhancing the host's immune response to combat tumors. Additionally, IPI-549 has been identified as a first-line therapeutic option for breast cancer treatment. The objective of this research was to develop and formulate a novel therapeutic supplement by combining dendritic cells with IPI-549 (Eganelisib) for breast cancer treatment. The concurrent administration of dendritic cells and IPI-549 (DC-IPI) was utilized to treat mice and elicit immunological responses triggered by vaccination. Tumor regression and overall survival rates were evaluated across five distinct experimental groups. The administration of tumor cell lysate alongside DC-IPI resulted in a significant reduction in tumor growth and a two- to three-fold increase in the survival duration of treated mice. DC-IPI, whether decorated with mannan or not, elicited stronger responses in terms of delayed-type hypersensitivity, lymphocyte proliferation, and CD107a expression. Moreover, our findings demonstrated a reduction in IL-4 production in the supernatants of splenocyte cultures. A significant reduction in BRCA1 mRNA levels was also observed following treatment with DC-IPI. In conclusion, our results suggest that the DC-IPI antigen delivery system exhibited substantial anti-tumor efficacy in a breast cancer mouse model, representing a potential advancement in immunotherapy for human breast cancer.

First-line treatment of EGFR-mutated non-small cell lung cancer with brain metastases: a systematic review and meta-analysis

This systematic review and network meta-analysis evaluates first-line treatment options for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases. We analyzed 24 randomized controlled trials (RCTs) involving 2,682 patients, comparing various EGFR tyrosine kinase inhibitors (TKIs) and combination therapies. Direct comparisons showed that the addition of bevacizumab or chemotherapy to first-generation (1G) EGFR-TKIs improved overall survival (OS) compared to 1G TKIs alone, with HRs of 0.704 (95% CI: 0.433–0.973) and 0.682 (95% CI: 0.464–0.899), respectively. However, third-generation (3G) TKI monotherapy did not significantly improve OS compared with 1G TKIs, with an HR of 0.855 (95% CI: 0.511–1.198). Indirect comparisons suggested that the combination of 3G TKIs with chemotherapy provided the most significant improvements in OS and progression-free survival (PFS), significantly outperforming 3G TKIs, with HRs of OS 1.69 (95% CI: 1.14–3.4) and PFS 2.13 (95% CI: 1.28–3.54). Intracranial PFS was best with 1G TKIs plus bevacizumab. Our findings suggest that 3G EGFR-TKIs in combination with chemotherapy may be the most effective strategy for patients with EGFR-mutant NSCLC and brain metastases, though further head-to-head trials are needed for validation.

Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab–Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis

IntroductionNivolumab plus ipilimumab–based treatment regimens have shown long-term, durable efficacy benefits in patients with metastatic NSCLC. Here we report clinical outcomes from a pooled analysis of patients with metastatic NSCLC and tumor programmed death-ligand 1 (PD-L1) lower than 1% treated with first-line nivolumab plus ipilimumab with or without two cycles of chemotherapy versus up to four cycles of chemotherapy in the randomized phase 3 CheckMate 227 and CheckMate 9LA studies. MethodsPatients were aged 18 years or older and had stage IV/recurrent NSCLC with no sensitizing EGFR/ALK alterations. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety. ResultsIn patients with tumor PD-L1 lower than 1% in the nivolumab plus ipilimumab with or without chemotherapy (n = 322) versus chemotherapy (n = 315) arms, median OS was 17.4 versus 11.3 months, respectively, (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.54–0.76; 5-y OS rate, 20% versus 7%) at a median follow-up of 73.7 months. The OS benefit was observed across key subgroups, including difficult-to-treat populations such as those with baseline brain metastases (HR = 0.44, 95% CI: 0.26–0.75) or squamous NSCLC (HR = 0.51, 95% CI: 0.36–0.72). In the overall pooled population, the median PFS was 5.4 versus 4.9 months (HR = 0.72, 95% CI: 0.60–0.87; 5-y PFS rate, 9% versus 2%), the objective response rate was 29% versus 22%, and the median duration of response was 18.0 versus 4.6 months. No new safety signals were observed. ConclusionNivolumab plus ipilimumab with or without chemotherapy provides a long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 lower than 1%, supporting the use of this strategy as a first-line treatment option in this population with high unmet need. Clinical Trial Registrations: NCT02477826, NCT03215706

Systemic Therapy Options for Peritoneal Mesothelioma.

Peritoneal mesothelioma is an uncommon malignancy affecting approximately 300 new patients annually in the United States. Due to its low incidence, prospective clinical trials specific to this disease are scant. Recommendations regarding systemic therapy are mostly extrapolated from clinical trials conducted among patients with pleural mesothelioma. At present, the recommended first-line systemic treatment options may include immunotherapy with nivolumab plus ipilimumab or chemotherapy with pemetrexed plus either cisplatin or carboplatin. For second-line treatment, the other previously unchosen first-line option can be used. Off-label bevacizumab may be considered in combination with chemotherapy among carefully selected patients. The benefit of third-line treatment or beyond is less clear. Nonetheless, a number of single-agent regimens show modest activity. Anecdotal reports of children or young adults with peritoneal mesothelioma harboring ALK rearrangement have suggested the efficacy of ALK inhibitors for this rare population. In summary, there is a growing number of systemic therapy options for peritoneal mesothelioma. To gain a better insight into this disease, future prospective trials in mesothelioma should include more patients with peritoneal mesothelioma.

Distribution of Certified Pelvic Health Physical Therapists Across the United States

Purpose: Pelvic floor dysfunction (PFD) describes a range of impairments affecting people of all genders. Pelvic health physical therapy (PHPT), a first-line treatment option for PFD, has been associated with improvements in myriad related conditions. This study aimed to examine the number of PHPT specialists in the United States and each state individually in order to assess distribution of care. We hypothesized that this number is low when compared with the estimated demand for services. Methods: This descriptive cross-sectional study identified PHPT specialists as those with a Certificate of Achievement in Pelvic Health Physical Therapy (CAPP-Pelvic), a Women’s Health Clinical Specialist (WCS) Board Certification, or a Pelvic Rehabilitation Practitioner Certification (PRPC), as of May 31, 2022. Researchers utilized 3 online databases to identify 1135 PHPT providers across the US and compared statewide data with current state population to determine providers per million people. Results: The number of PHPT providers per state ranged from 1 (Vermont) to 119 (California). When compared to state population, the lowest PHPT provider ratio was approximately 1 per million people (Alabama) and the highest was approximately 8 per million people (Oregon). Discussion: The data indicate that the number of PHPT providers available varies by state. The number of PHPT providers in the US is low overall and relative to states’ populations. Given the prevalence of PFD in the US, it is unlikely that the total number of providers in most states is sufficient to meet clinical demands.

A Dedicated Algorithm for Endovascular Approach as a First-Line Treatment Option for Visceral Artery Aneurysms

Few data are reported in literature about visceral artery aneurysms (VAAs) management. The aim of the present study was to analyze VAAs management in a single institution, with a dedicated algorithm for endovascular approach as the first line treatment. A single-center retrospective cohort study was performed. Patients with a VAA submitted to either endovascular repair or open surgery from 2016 to 2023 were included. A dedicated algorithm was used to evaluate the endovascular approach feasibility assessing on the preoperative computed tomography angiography the following parameters: (a) the tortuosity of the involved artery (<150°), (b) the healthy arterial diameter (>4mm), (c) the VAA proximity to the hilum and/or the presence of a bifurcation of the aneurysmatic artery, and (d) the circumferential calcium presence. An endovascular approach was chosen if (a) and (b) criteria were satisfied without (c) and (d) ones. Otherwise, it was deemed a challenging anatomy, and an open surgical treatment was considered. In the absence of (a) and/or (b) criteria open surgery was the preferred option. Thirty-one asymptomatic aneurysms (28 patients) were treated electively. The most frequent VAA location was the splenic artery (18 cases; 58%), followed by the renal arteries (6 cases; 19%), the common hepatic artery (5 cases; 16%), the gastroepiploic artery (1 case, 3.2%) and the pancreatoduodenal artery (1 case; 3%). Twenty-two aneurysms (71%) were initially treated by an endovascular approach (stent-graft deployment and/or transcatheter embolization) with 3 (13%) of them needing a surgical conversion. Nine aneurysms (29%) were submitted directly to a surgical treatment (aneurysm resection with or without interposition bypass) with no peri-operative and long-term complications. Technical success was 90.3%. Endovascular management as a first line approach is safe and effective in most cases. A preoperative dedicated algorithm is useful to identify suitable cases. Open surgery can be considered an alternative option in specific challenging anatomical situations or in case of endovascular failure.