Sex Therapy Research Articles

Association among major adverse cardiovascular events with immune checkpoint inhibitors: A systematic review and meta-analysis.

This meta-analysis aimed to determine the incidence and overall risk of major adverse cardiovascular events (MACEs) related to immune checkpoint inhibitors (ICIs). We systematically searched all cohort studies, including the available MACE data in cancer patients receiving ICIs, in PubMed, Embase, and the Cochrane Library, from their inception to September 5, 2023. The primary outcome was the incidence of MACEs associated with ICI exposure, and the secondary outcome was the overall risk of MACEs associated with ICI exposure versus non-ICI exposure controls. Risk ratios with 95% confidence intervals were used in the random- or fixed-effects models. Overall, 26 cohort studies met the inclusion criteria, involving 109,883 cancer patients. In the median follow-up period ranging from 3.3 to 55.2 months, the incidence of MACEs associated with ICI exposure was 8.22%, ranging from 0.55% to 3.98%, among the nine MACEs, including myocarditis, tachyarrhythmia, pericarditis, pericardial effusions, cardiovascular death, myocardial infarction, heart failure, stroke, and conduction disorder. The incidence of MACE associated with non-ICI exposure was 3.84%, ranging from 0.81% to 4.72%. The risks of all-grade MACEs and pericardial effusions were significantly higher in the ICI group than in the non-ICI controls. ICI treatment, age, male sex, and prior radiation therapy were significantly associated with MACEs. The risk of MACEs during ICI treatment in patients with cancer is more common than is currently recognized. ICI use is closely associated with an increased risk of MACEs. Patients at risk were older, male, and had a history of radiation therapy.

PATH-26. MIDLINE INVOLVEMENT IS ASSOCIATED WITH ABERRANT RB1 SIGNALING IN PATIENTS WITH GRADE 4 IDH-MUTANT ASTROCYTOMA

Abstract BACKGROUND The prognostic factors impacting the survival of grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide are not well-described. METHODS A retrospective cohort was generated of all patients diagnosed at Mayo Clinic with grade 4 IDH-mutant astrocytoma (2021 WHO Classification) on initial diagnosis between 2002-2023, and who received standard radiation/temozolomide. The impact of patient, tumor and molecular variables on overall survival (OS) and progression-free survival (PFS) was evaluated using survival analyses and Cox regression models. RESULTS Fifty-eight patients were identified. The median age was 36 years, 64% were male and 93% were white. The median follow up was 3.3 years. The median OS and PFS were 6.9 years and 2.4 years, respectively. CDKN2A/B homozygous deletion significantly reduced both OS (2.5 years vs NR, HR=3.9, p=0.0168) and PFS (1.4 vs 4.5 years, HR=4.2, p=0.0005). Midline involvement (brainstem, basal ganglia, thalamus, cerebellum or corpus callosum) also significantly reduced both OS (2.4 vs 12.8 years, HR=7.0, p=0.0014) and PFS (1.4 vs 4.5 years, HR=4.8, p=0.0002). MGMT promoter hypermethylation showed a trend toward significance for PFS (p=0.082) but did not impact OS. Age, sex, tumor size, ATRX immunohistochemistry and tumor-treating field therapy did not impact survival outcomes. Multivariable analyses revealed that PFS remained significantly impacted by both CDKN2A/B homozygous deletion (HR=3.5, p=0.0051) and midline involvement (HR=3.1, p=0.0125). A significant association between CDKN2A/B homozygous deletion and midline involvement was unexpectedly observed (53% if midline, 24% if non-midline; χ2=4.3, p=0.037). Exploratory analyses revealed that 15/15 (100%) of patients with midline involvement demonstrated aberration in RB1 signaling (CDKN2A/B homozygous deletion, n=8; CDKN2A/B hemizygous deletion or loss of heterozygosity, n=6; CDK4 amplification, n=1). CONCLUSION CDKN2A/B homozygous deletion and midline involvement independently impact PFS in patients with grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide. Furthermore, midline involvement may be associated with aberrant RB1 signaling.

PATH-23. SARCOMATOUS TRANSFORMATION OF GLIOBLASTOMA IS ASSOCIATED WITH A DISTINCT MOLECULAR SIGNATURE

Abstract A subset of IDH-wildtype glioblastoma (GBM) undergo sarcomatous transformation to gliosarcoma at recurrence which is associated with a propensity for dural and calvarial invasion. However, the underlying biology of sarcomatous transformation and predictive biomarkers for these aggressive tumors are unknown. We performed comprehensive histopathologic, genomic, and epigenomic evaluation of paired initial and recurrent GBM from 106 patients. Eighteen patients (17%) developed sarcomatous transformation at recurrence as defined by fascicular growth, intercellular reticulin deposition, and immunohistochemical evidence of glial to mesenchymal transdifferentiation. Compared to conventional GBM, patients who developed gliosarcoma had shorter interval between initial surgery and first recurrence (8.3 vs. 11.2 months, p=0.002) and reduced overall survival (18.2 vs. 21.9 months, p=0.164). While there were no differences in sex, age, tumor location, or adjuvant therapy, we found differences in the molecular signatures of GBM that transformed to gliosarcoma at recurrence, including a significant enrichment in NF1, TP53, and RB1 alterations and an absence of EGFR amplification. GBM which underwent sarcomatous transformation were enriched for the Mesenchymal epigenetic class at initial surgery (69% vs. 25%) and became enriched for the novel Mesenchymal subclass B at recurrence (43% vs. 2%). Among approximately 850,000 interrogated CpG sites, we identified 1,503 and 2,090 CpG sites within gene regulatory regions that were significantly more hypermethylated or hypomethylated in those initial GBM that transformed to gliosarcoma at recurrence compared to those that did not. Gene Ontology biologic processes enriched in these differentially methylated genes include immune cell signaling, cell-cell adhesion, and TGF-beta signaling. Together, these findings reveal GBM which undergo transformation to gliosarcoma represent a biologically distinct subtype with aggressive clinical course. Enrichment for NF1 and RB1 alterations and differentially methylated immune cell and TGF-beta signaling suggests potential unique therapeutic vulnerabilities for affected patients.

Immune Activation Is Associated With Neurocognitive Performance in Ugandan Adolescents Living With HIV.

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 sociodemographically matched HIV-negative controls), completed a tablet-based neurocognitive test battery. Control-derived z-scores for 12 individual tests and a global/overall z-score were calculated. We measured plasma (soluble CD14 and CD163), monocyte (proportions of monocyte subsets), and T-cell (expression of CD38 and HLA-DR on CD4 + and CD8 + ) activation and gut markers. Spearman rank correlations and median regressions examined associations between test performance and immune activation. The median [IQR] age was 15 [13-16] years, and 40% were girls. The median time on antiretroviral therapy was 10 years [7-11] for PHIV; 87% had viral load <50 copies/mL. Compared with controls, global z-scores were lower among PHIV ( P = 0.05) and significantly worse on tests of executive functioning and delayed recall ( P 's ≤ 0.05). Overall, monocyte activation significantly correlated with worse test performance on global z-score (r = 0.21, P = 0.04), attention, processing speed, and motor speed (r = 0.2-0.3, P ≤ 0.01). T-cell activation was significantly correlated with worse performance on tests of learning, executive functioning, and working memory (r = 0.2-0.4, P ≤ 0.04). In PHIV, after adjusting for age, sex, and antiretroviral therapy duration, activated CD4 T cells remained associated with worse memory (β-0.3, 95% CI: -0.55 to -0.07, P = 0.01). PHIV with virologic suppression on antiretroviral therapy shows evidence of worse neurocognitive test performance compared with controls. Monocyte and T-cell activation is correlated with worse neurocognition in Ugandan youth with and without HIV, which has not been previously investigated in this setting.

Results of a randomized waitlist-controlled trial of online cognitive behavioral sex therapy and online mindfulness-based sex therapy for hypoactive sexual desire dysfunction in women.

This study aimed to investigate the efficacy of two internet-delivered psychological treatments for hypoactive sexual desire dysfunction (HSDD) in women: internet-based cognitive behavioral sex therapy (iCBST) and internet-based mindfulness-based sex therapy (iMBST). Women with HSDD were randomly assigned to one of three groups: iCBST, iMBST, or a waitlist control group. The interventions consisted of eight modules delivered via an e-health platform with e-coach support to enhance adherence. Sexual desire and sexual distress were assessed at baseline and at 3-, 6-, and 12-month follow-ups (active conditions only). Per protocol, of the 266 consenting women, 106 were randomized to iCBST (Mage = 36.1, SD = 10.3), 106 to iMBST (Mage = 36.4, SD = 0.2), and 54 to the control condition (Mage = 36.7, SD = 11.0). Primary analyses utilized an intention-to-treat approach with linear mixed models. Clinical significance, assessed with clinical cutoffs and the reliable change index, was examined for active conditions. Compared to the control condition, both iCBST and iMBST demonstrated significant improvements in sexual desire and sexual distress at 3-month (d = 0.89-1.14) and 6-month follow-up (d = 0.74-1.18). Results were sustained at 12-month follow-up, with 35 and 41% demonstrating reliable improvements and additional 20 and 24% achieving clinically significant improvements in sexual desire after iCBST and iMBST. Regarding sexual distress, 49 and 42% exhibited reliable change, with an additional 37%-42% achieving clinically significant improvements. Results provide support for the overall long-term efficacy of psychological therapies in treating HSDD in women. However, fewer than one in four women showed improvements in sexual desire that met the threshold for clinically significant change. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Postmenopausal dyspareunia.

Dyspareunia in the postmenopausal woman is often multifactorial and requires a thorough history, a targeted physical examination, and coordination of multiple disciplines, including medical professionals, pelvic floor physical therapists, and sex therapists. Although we have come a long way since early assessments of painful sex, evaluation and treatment of dyspareunia remain an unmet need. This is particularly true in postmenopausal women in whom it is commonly assumed that pain with penetrative sex is solely a consequence of atrophy.

Supplemental Material for Results of a Randomized Waitlist-Controlled Trial of Online Cognitive Behavioral Sex Therapy and Online Mindfulness-Based Sex Therapy for Hypoactive Sexual Desire Dysfunction in Women

Supplemental Material for Results of a Randomized Waitlist-Controlled Trial of Online Cognitive Behavioral Sex Therapy and Online Mindfulness-Based Sex Therapy for Hypoactive Sexual Desire Dysfunction in Women

Risk of Revictimization within Intimate Relationships among Women Survivors of Childhood Sexual Abuse: The Role of Cumulative Trauma and Self-Capacities Disturbances

Childhood sexual abuse, especially in the context of cumulative childhood interpersonal trauma (CCIT), is associated with an increased risk of revictimization by an intimate partner among women. The aim of the present study is to examine the role of self-capacities disturbances in the association between CCIT and revictimization by an intimate partner. The sample comprised of 247 adult women survivors consulting in sex therapy. Path analyses showed an indirect effect of self-capacities disturbances in the association between CCIT and revictimization (ORs = 1.49 and 1.62), demonstrating the importance of intervening in relational and affective difficulties among women survivors to prevent the risk of revictimization.

DISCREPANCY BETWEEN PATIENT VERSUS PROVIDER ASSESSMENT OF ERECTION QUALITY

ObjectiveTo characterize the discrepancy between patients’ and providers’ assessments of erection rigidity and its association with patient characteristics and penile ultrasound parameters. MethodsPatients presenting for penile doppler ultrasound between July 2022 and October 2023 were reviewed retrospectively. After intracavernosal injection, patients and providers independently rated erection rigidity from 1 to 10 prior to ultrasound. We defined discrepancy as a difference of 2 out of 10 or greater between the two assessments. Chi-squared and Mann Whitney U tests were used for hypothesis testing. Results65/297 (22%) of patients demonstrated a discrepancy in perceived erection quality. 58/65 (89%) of these patients rated their erections lower than their providers. There was a higher incidence of ED as the primary diagnosis in the discrepant group as compared to the concordant group (p=0.01). The discrepant group also showed a higher resistive index on penile ultrasound (p=0.04), with no difference in peak systolic velocity, end diastolic velocity, or other clinical variables between the two groups. ConclusionDiscrepancy in perceived erection rigidity was mainly driven by lower patient perception, although these patients had noninferior penile hemodynamics to their peers. These findings underscore the influence of subjective perception of virility on sexual function. It is critical for clinicians to identify patients with poor perception of erectile function out of proportion to physiologic abnormalities. Thoughtful counseling about treatment goals and expectations, emphasizing functional outcomes, and adjunctive treatments such as sex therapy or psychotherapy are critical to therapeutic success in this population.

A brief package of tele-sexual counseling based on Islamic emotion-focused therapy versus tele-sexual health education on sexual intimacy in pregnant women: A randomized clinical trial

BACKGROUND: Physical and emotional changes in pregnancy may reduce sexual intimacy. Pregnant women need empowerment through short-term cultural-based interventions regarding sexual intimacy for better expression of sexual beliefs and expectations. Since studies are limited regarding Islamic emotion-focused therapy (IEFT), this study was conducted to compare the effect of tele-sexual counseling (IEFT) versus tele-sexual health education on sexual intimacy in pregnant women. MATERIALS AND METHODS: A parallel randomized clinical trial was conducted among 52 pregnant women with gestational age at least 20–24 weeks through convince sampling referred to Amir Social Welfare Clinic, who were randomly assigned into two groups (each group = 26 women). The intervention group received online six weekly IEFT, and the control group participated in online sexual health education. Primary outcome sexual intimacy was measured via Botlani’s sexual intimacy questionnaire at baseline, end of intervention at week 6, and follow-up at week 10. Secondary outcome satisfaction was assessed via a satisfaction scale at weeks 6 and 10 of the intervention. Data were analyzed using Mann–Whitney, the T-test, the analysis of variance, and repeated measures in SPSS. RESULTS: Sexual intimacy was not significantly different between the two groups at baseline. Sexual intimacy was significantly high in the intervention group in weeks 6 (intervention group: 83.12 ± 5.22 versus control group: 70.62 ± 4.42) (P &lt; 0.001) and 10 (intervention group: 84.08 ± 5.03 versus control group: 70.54 ± 4.37) (P &lt; 0.001). Satisfaction in week 6 was 52.38 ± 10.48 in the intervention group versus 42.69 ± 10.98 in the control group (P = 0.001), and at week 10, it was 55.58 ± 10.71 in the intervention group versus 45.12 ± 11.56 in the control group (P = 0.001), with more satisfaction in the intervention group. CONCLUSION: Both short-term tele-interventions, IEFT or sexual health, improved sexual intimacy and satisfaction, but Islamic EFT was significantly superior. It seems women need cultural-religious-based interventions such as IEFT to facilitate positive sexual relationship changes, assertiveness in sexual emotion expression, and compassion through the sharing of skills with the husband that can continue individually even after intervention. The study findings can be applied to midwifery education, prenatal care booklets, couple and sex counselors and therapists, and other health care providers.

Mastering Ejaculation Challenges Through Comprehensive Strategies: A Case Report

Background This case report explores the successful management of psychogenic anejaculation in a 31-year-old poultry farmer. Despite an 8-year history of anejaculation during intercourse, the patient achieved ejaculation during masturbation. Initial pharmacological intervention with duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, provided partial success. To address persisting challenges, dual sex therapy and sensate focus therapy were introduced, based on the work of Masters and Johnson. The integrated approach proved effective, leading to successful ejaculation and the conception of the patient's wife. This case emphasizes the necessity of a comprehensive approach to psychological anejaculation, combining pharmacological and psychotherapeutic interventions for successful outcomes.

When sexual distress shares the bed: the role of sexual self-esteem in the relationship between dispositional mindfulness and sexual distress in sex therapy patients.

Sexual distress (eg, feeling distressed, unhappy, frustrated, stressed, dissatisfied, or bothered about their sexuality) is a central concern reported by patients seeking sex therapy, and might be related to sexual self-esteem and mindfulness disposition, yet research is needed to examine the links among those variables within the specific population of patients seeking therapy. This study aimed to examine the indirect role of sexual self-esteem in the relationship between dispositional mindfulness and sexual distress. The study was conducted among 696 patients undergoing sexual therapy (mean age 34.19 ± 11.21 years, age range 18-78years). Participants identified as women (57.3%), men (38.5%), or nonbinary (4.2%). They completed self-report questionnaires assessing dispositional mindfulness (Five Facet Mindfulness Questionnaire), sexual self-esteem (Multidimensional Sexuality Questionnaire), and sexual distress (Sexual Distress Scale-Revised), during their first few sessions (ie, first to third sessions [the assessment phase]). Sexual distress was the main outcome, as measured with the Sexual Distress Scale-Revised. Results indicated that 54% (n = 376) of patients reported elevated sexual distress based on the questionnaire threshold score. Path analyses indicated an indirect effect in which higher dispositional mindfulness was associated with higher levels of sexual self-esteem, which in turn was associated with lower sexual distress. Results also highlighted that specific facets of mindfulness were related to higher sexual self-esteem (ie, describing, and nonreacting) and lower sexual distress (ie, nonjudgment and acting with awareness). The integrative model explained 23% of the variance of sexual distress scores. Findings suggest that addressing specifically sexual self-esteem and mindfulness may represent relevant clinical avenues to reduce sexual distress among sex therapy patients. Strengths of this study include the novel examination of the role of sexual self-esteem in the link between mindfulness disposition and sexual distress in a large clinical sample of patients seeking sex therapy. Limitations includes reliance on patient self-report and a cross-sectional design that limit conclusion regarding causality. This study makes a valuable contribution to the existing body of research highlighting the pivotal roles of sexual self-esteem in the link between dispositional mindfulness and reduced sexual distress among adults undergoing sex therapy, allowing us to identify potential targets of intervention.

Unveiling sex-disparities and the impact of gender-affirming hormone therapy on periodontal health

IntroductionAs personalized medicine advances, the need to explore periodontal health across different sexes and gender identities becomes crucial. This narrative review addresses the gap in understanding how biological sex and gender-affirming hormone therapy (GAHT) influence periodontitis risk.ResultsResearch has uncovered significant sex-based immunological disparities driven by X and Y chromosome gene expression and sex-hormones, which may influence susceptibility to periodontitis. Additionally, preliminary findings suggest that GAHT, particularly testosterone therapy in transgender men, could exacerbate pro-inflammatory cytokine production and alter immune cell responses, which may exacerbate inflammatory pathways crucial in the progression of periodontitis. Conversely, the effects of estrogen therapy in transgender women, although less extensively studied, suggest modifications in B cell functionality. These observations highlight the complex role of GAHT in modulating immune responses that are central to the development and exacerbation of periodontal disease.DiscussionThe review highlights a complex interaction between sex hormones, gene expression patterns, immune responses, and periodontitis risk. While cisgender males show increased susceptibility to periodontitis that could be linked to specific immune pathways, GAHT appears to modify these pathways in transgender individuals, potentially altering their risk and disease progression patterns.ConclusionThere is a critical need for more focused research on the direct impacts of GAHT on periodontal health. Understanding the nuances of immune modulation by GAHT will aid in crafting personalized periodontal care for transgender individuals, aligning with the broader goals of inclusive and effective healthcare.

Postoperative bowel dysfunction in patients with rectal cancer – Does a minimally invasive surgical approach improve outcomes?

IntroductionThe purpose of this study was to evaluate the association of MIS approaches for rectal cancer with long-term postoperative bowel dysfunction. Materials and methodsThis was an Institutional Review Board-approved observational cohort study including consecutive patients with rectal or rectosigmoid cancer who underwent surgical resection between 2007 and 2017. The primary exposure was surgical approach, defined as open surgery or MIS (laparoscopy or robotic surgery). The primary outcome was major LARS, defined as a LARS score of ≥30. Subgroup analyses were performed by tumor height and type of MIS approach. ResultsAmong 749 potentially eligible patients, 514 (68.6 %) responded to the survey and were included for analysis. In total, 195 (37.9 %) patients underwent an MIS approach – 117 (60.0 %) laparoscopic and 78 (40.0 %) robotic. At a median follow-up of 6.1 (3.7–9.6) years from surgery, 222 patients (43.2 %) had major LARS (MIS: 41.0 % vs. open: 44.5 %, p = 0.44). On multivariable logistic regression, surgical approach had no association with major LARS (MIS, aOR: 1.21, 0.79–1.86). Older age (aOR: 1.03, 1.01–1.04), female sex (aOR: 1.75, 1.16–2.67), TME (aOR: 1.74, 1.01–3.02), diverting ileostomy (aOR: 2.74, 1.49–5.02) and radiation therapy (aOR: 2.63, 1.60–4.33) were all associated with major LARS. On subgroup analysis of patients with mid and low rectal cancers (n = 197), there remained no association between surgical approach and major LARS (MIS, aOR: 1.50, 0.68–3.33). ConclusionsMIS approach to rectal cancer surgery was not associated with decreased risk of major LARS and should not be touted as a reason to offer MIS.

Sexual health and wellbeing and the menopause: An EMAS clinical guide

IntroductionSexual health and wellbeing are significant aspects of quality of life. However, taking a sexual history is often avoided in medical practice, leaving a void in management and awareness. As the menopause can have a major impact on sexual health, it is imperative that healthcare providers are appropriately trained in sexual health and wellbeing and the aligned disciplines in order to achieve optimal care. AimTo provide an evidence-based clinical guide for the assessment and management of sexual problems at the menopause and beyond. Materials and methodsReview of the literature and consensus of expert opinion. Results and conclusionThe assessment of sexual problems includes history taking, examination and laboratory investigation (if indicated), and occasionally the use of specific validated questionnaires. Management of sexual problems requires a multidimensional approach using biopsychosocial measures. Medical management and psychosexual counselling include pharmacological and non-pharmacological interventions, and sex therapy and psychoeducation. Furthermore, perimenopausal women should be advised about the need for contraception if they wish to avoid pregnancy. Also, sexually transmitted diseases can be acquired at any age. To conclude, taking a sexual history should be incorporated into medical practice and healthcare providers should be appropriately trained to assess and manage sexual problems at the menopause and beyond.

Sexual health after breast cancer: a clinical practice review.

Breast cancer (BC) diagnoses not only present physical challenges but profoundly affect survivors' psychosocial well-being leading to sexual health challenges. This clinical practice review aimed to discuss the current literature and outline the knowledge gaps related to care for sexual health after BC, including survivors' sexual health concerns, as well as available prospective surveillance programs. Current literature on the sexual health challenges of BC survivors was identified and sorted into contributing factors, treatments and interventions, and practice recommendations. This evidence was then used to identify gaps in the literature and make recommendations for future research. BC survivors experience a variety of physical symptoms, such as pain during sex or dyspareunia, which impair sexual well-being. Additionally, dissatisfaction with sexual function may arise due to psychosocial stressors (e.g., depression or body image concerns) and the inverse may worsen psychological well-being. Treatments can have lasting effects that may impact sexual function, often reciprocally related to physical and psychosocial factors. Current treatments for sexual dysfunction involve topical products for vaginal symptoms (e.g., creams, pH-balanced gels, hyaluronic acid or vitamin E suppositories, natural oils, topical estrogen, or lubricants) and various counseling and educational interventions (e.g., mental health counseling, sex therapy, or couples-based psychotherapy). There is a general lack of research considering the ways in which intersectional concerns can impact sexual health experiences after BC. Existing studies do not often consider potential differences in needs that may arise due to ethnicity, age, or socioeconomic background. To address these limitations a significant paradigm shift in survivorship care. This requires moving beyond disease management towards a more holistic, comprehensive, patient-centered approach prioritizing comfort and sexual well-being.

Risk Factors Associated with Antibiotic Exposure Variability in Critically Ill Patients: A Systematic Review.

(1) Background: Knowledge about the behavior of antibiotics in critically ill patients has been increasing in recent years. Some studies have concluded that a high percentage may be outside the therapeutic range. The most likely cause of this is the pharmacokinetic variability of critically ill patients, but it is not clear which factors have the greatest impact. The aim of this systematic review is to identify risk factors among critically ill patients that may exhibit significant pharmacokinetic alterations, compromising treatment efficacy and safety. (2) Methods: The search included the PubMed, Web of Science, and Embase databases. (3) Results: We identified 246 observational studies and ten clinical trials. The most studied risk factors in the literature were renal function, weight, age, sex, and renal replacement therapy. Risk factors with the greatest impact included renal function, weight, renal replacement therapy, age, protein or albumin levels, and APACHE or SAPS scores. (4) Conclusions: The review allows us to identify which critically ill patients are at a higher risk of not reaching therapeutic targets and helps us to recognize the extensive number of risk factors that have been studied, guiding their inclusion in future studies. It is essential to continue researching, especially in real clinical practice and with clinical outcomes.

Increase in major osteoporotic fractures after therapy with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) can cause severe and sometimes long-standing immune-related adverse events (irAEs). Enhanced immune activation from ICI can theoretically result in osteoclast activation, bone loss and fracture. The...

Outcomes in non-small cell lung cancer with uncommon epidermal growth factor receptor L858 substitutions under first-line epidermal growth factor receptor tyrosine kinase inhibitors: A large real-world cohort study.

Atypical L858R or other L858X mutations in the epidermal growth factor receptor (EGFR) gene, beyond the classical EGFRL858R mutation caused by c.2573 T > G, have been identified in non-small cell lung cancer (NSCLC), yet their genomic features and survival benefits with EGFR tyrosine kinase inhibitor (TKI) treatment have not been fully explored. We retrospectively enrolled 489 NSCLC patients with baseline tumor tissue/plasma samples carrying uncommon EGFRL858R (N = 124), EGFRL858Q/M (N = 17), or classical EGFRL858R mutations (N = 348). The comparison of molecular features was performed using treatment-naïve tumor tissues. Survival benefits and resistance mechanisms of first-line EGFR TKI treatment were studied in an advanced disease subcohort. NSCLCs harboring uncommon EGFRL858R had lower TP53 mutation prevalence (p = 0.04) and chromosome instability scores (p = 0.02) than those with classical EGFRL858R. Concomitant EGFRL861Q mutations were enriched in NSCLCs with EGFRL858Q/M (p < 0.01), with cooccurrence in those carrying EGFRL858M. Patients with uncommon EGFRL858R experienced improved progression-free survival (PFS) compared to those with classical EGFRL858R (median: 13.0 vs. 10.0 months, hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.41-0.80). The association remained significant when adjusting for sex, age, histological subtype, TKI category, and anti-vascular therapy (HR: 0.55, 95% CI: 0.39-0.77). Furthermore, EGFRL858Q/M patients showed enhanced first-line PFS (vs. classical EGFRL858R, HR: 0.26, 95% CI: 0.10-0.67), potentially benefiting more from afatinib. Additionally, NSCLCs with uncommon EGFRL858R and classical EGFRL858R had similar resistance profiles to EGFR TKIs. In conclusion, NSCLCs carrying atypical EGFR L858 aberrations, which had fewer TP53 mutations and higher chromosome stability, exhibited improved PFS under first-line EGFR TKIs than those with the classical EGFRL858R.

Chronic Obstructive Pulmonary Disease and the Omicron Variant of COVID-19 Prognosis: A Retrospective Cohort Study.

This retrospective cohort study aimed to investigate the association between chronic obstructive pulmonary disease (COPD) and the prognosis of COVID-19 patients infected with the Omicron variant. The primary objective was to determine if COVID-19 patients with COPD had higher mortality rates compared to those without COPD. Secondary objectives included assessing the risk of respiratory failure, hospital stay length, intensive care unit (ICU) admission, and oxygen requirements in COPD patients with COVID-19. The study included 2761 COVID-19 patients admitted to the Princess Margaret Hospital, Hong Kong, between January 1 and June 30, 2022. Among them, 7.4% (n = 205) had COPD. Demographic and clinical data, including vaccination status and comorbidities, were collected. The primary outcome was 30-day mortality, and secondary outcomes included respiratory support requirement, hospital stay length, and ICU admission. Logistic regression analyses were conducted, adjusting for potential confounders. COPD did not independently increase the risk of COVID-19 mortality after adjusting for confounders. Instead, older age, male sex, incomplete vaccination, long-term oxygen therapy use, and specific comorbidities were identified as significant predictors of 30-day mortality. COPD patients were more likely to require oxygen and noninvasive ventilation, but there were no significant differences in other secondary outcomes compared to non-COPD patients. COPD itself was not an independent risk factor for COVID-19 mortality. Age, sex, vaccination status, comorbidities, and long-term oxygen therapy use were important predictors of mortality. These findings underscore the importance of considering multiple factors when assessing the impact of COPD on COVID-19 prognosis, particularly with the Omicron variant.