Detection of elusive DNA copy-number variations in hereditary disease and cancer through the use of noncoding and off-target sequencing reads.

Copy-number variants (CNVs) play a substantial role in the molecular pathogenesis of hereditary disease and cancer, as well as in normal human interindividual variation. However, they are still rather difficult to identify in mainstream sequencing projects, especially involving exome sequencing, because they often occur in DNA regions that are not targeted for analysis. To overcome this problem, we developed OFF-PEAK, a user-friendly CNV detection tool that builds on a denoising approach and the use of "off-target" DNA reads, which are usually discarded by sequencing pipelines. We benchmarked OFF-PEAK on data from targeted sequencing of 96 cancer samples, as well as 130 exomes of individuals with inherited retinal disease from three different populations. For both sets of data, OFF-PEAK demonstrated excellent performance (>95% sensitivity and >80% specificity vs. experimental validation) in detecting CNVs from in silico data alone, indicating its immediate applicability to molecular diagnosis and genetic research.

Paradoxical activation of oncogenic signaling as a cancer treatment strategy.

Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity of such aberrant signaling. While inhibition of oncogenic signaling pathways has been explored extensively, there is increasing evidence that overactivation of the same pathways can also disrupt cancer homeostasis and cause lethality. We show here that inhibition of Protein Phosphatase 2A (PP2A) hyperactivates multiple oncogenic pathways and engages stress responses in colon cancer cells. Genetic and compound screens identify combined inhibition of PP2A and WEE1 as synergistic in multiple cancer models by collapsing DNA replication and triggering premature mitosis followed by cell death. This combination also suppressed the growth of patient-derived tumors in vivo. Remarkably, acquired resistance to this drug combination suppressed the ability of colon cancer cells to form tumors in vivo. Our data suggest that paradoxical activation of oncogenic signaling can result in tumor suppressive resistance.

SIV Infection Is Associated with Transient Acute-Phase Steatosis in Hepatocytes In Vivo.

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the timing of pathologic changes. The livers of both SIV-infected (N = 9) and SIV-naïve uninfected (N = 8) macaques were biopsied and evaluated at four time points (weeks -4, 2, 6, and 16-20 post-infection) and at necropsy (week 32). SIV DNA within the macaques' livers varied by over 4 logs at necropsy, and liver SIV DNA significantly correlated with SIV RNA in the plasma throughout the study. Acute phase liver pathology (2 weeks post-infection) was characterized by evidence for fat accumulation (microvesicular steatosis), a transient elevation in both AST and cholesterol levels within the serum, and increased hepatic expression of the PPARA gene associated with cholesterol metabolism and beta oxidation. By contrast, the chronic phase of the SIV infection (32 weeks post-infection) was associated with sinusoidal dilatation, while steatosis resolved and concentrations of AST and cholesterol remained similar to those in uninfected macaques. These findings suggest differential liver pathologies associated with the acute and chronic phases of infection and the possibility that therapeutic interventions targeting metabolic function may benefit liver health in people newly diagnosed with HIV.

Knowledge distillation on individual vertebrae segmentation exploiting 3D U-Net.

Recent advances in medical imaging have highlighted the critical development of algorithms for individual vertebral segmentation on computed tomography (CT) scans. Essential for diagnostic accuracy and treatment planning in orthopaedics, neurosurgery and oncology, these algorithms face challenges in clinical implementation, including integration into healthcare systems. Consequently, our focus lies in exploring the application of knowledge distillation (KD) methods to train shallower networks capable of efficiently segmenting vertebrae in CT scans. This approach aims to reduce segmentation time, enhance suitability for emergency cases, and optimize computational and memory resource efficiency. Building upon prior research in the field, a two-step segmentation approach was employed. Firstly, the spine's location was determined by predicting a heatmap, indicating the probability of each voxel belonging to the spine. Subsequently, an iterative segmentation of vertebrae was performed from the top to the bottom of the CT volume over the located spine, using a memory instance to record the already segmented vertebrae. KD methods were implemented by training a teacher network with performance similar to that found in the literature, and this knowledge was distilled to a shallower network (student). Two KD methods were applied: (1) using the soft outputs of both networks and (2) matching logits. Two publicly available datasets, comprising 319 CT scans from 300 patients and a total of 611 cervical, 2387 thoracic, and 1507 lumbar vertebrae, were used. To ensure dataset balance and robustness, effective data augmentation methods were applied, including cleaning the memory instance to replicate the first vertebra segmentation. The teacher network achieved an average Dice similarity coefficient (DSC) of 88.22% and a Hausdorff distance (HD) of 7.71 mm, showcasing performance similar to other approaches in the literature. Through knowledge distillation from the teacher network, the student network's performance improved, with an average DSC increasing from 75.78% to 84.70% and an HD decreasing from 15.17 mm to 8.08 mm. Compared to other methods, our teacher network exhibited up to 99.09% fewer parameters, 90.02% faster inference time, 88.46% shorter total segmentation time, and 89.36% less associated carbon (CO2) emission rate. Regarding our student network, it featured 75.00% fewer parameters than our teacher, resulting in a 36.15% reduction in inference time, a 33.33% decrease in total segmentation time, and a 42.96% reduction in CO2 emissions. This study marks the first exploration of applying KD to the problem of individual vertebrae segmentation in CT, demonstrating the feasibility of achieving comparable performance to existing methods using smaller neural networks.

Knee landmarks detection via deep learning for automatic imaging evaluation of trochlear dysplasia and patellar height.

OBJECTIVES: To develop and validate a deep learning-based approach to automatically measure the patellofemoral instability (PFI) indices related to patellar height and trochlear dysplasia in knee magnetic resonance imaging (MRI) scans. METHODS: A total of 763 knee MRI slices from 95 patients were included in the study, and 3393 anatomical landmarks were annotated for measuring sulcus angle (SA), trochlear facet asymmetry (TFA), trochlear groove depth (TGD) and lateral trochlear inclination (LTI) to assess trochlear dysplasia, and Insall-Salvati index (ISI), modified Insall-Salvati index (MISI), Caton Deschamps index (CDI) and patellotrochlear index (PTI) to assess patellar height. A U-Net based network was implemented to predict the landmarks' locations. The successful detection rate (SDR) and the mean absolute error (MAE) evaluation metrics were used to evaluate the performance of the network. The intraclass correlation coefficient (ICC) was also used to evaluate the reliability of the proposed framework to measure the mentioned PFI indices. RESULTS: The developed models achieved good accuracy in predicting the landmarks' locations, with a maximum value for the MAE of 1.38 ± 0.76 mm. The results show that LTI, TGD, ISI, CDI and PTI can be measured with excellent reliability (ICC > 0.9), and SA, TFA and MISI can be measured with good reliability (ICC > 0.75), with the proposed framework. CONCLUSIONS: This study proposes a reliable approach with promising applicability for automatic patellar height and trochlear dysplasia assessment, assisting the radiologists in their clinical practice. CLINICAL RELEVANCE STATEMENT: The objective knee landmarks detection on MRI images provided by artificial intelligence may improve the reproducibility and reliability of the imaging evaluation of trochlear anatomy and patellar height, assisting radiologists in their clinical practice in the patellofemoral instability assessment. KEY POINTS: • Imaging evaluation of patellofemoral instability is subjective and vulnerable to substantial intra and interobserver variability. • Patellar height and trochlear dysplasia are reliably assessed in MRI by means of artificial intelligence (AI). • The developed AI framework provides an objective evaluation of patellar height and trochlear dysplasia enhancing the clinical practice of the radiologists.

Have we improved postoperative and long-term outcomes of liver surgery for colorectal cancer metastasis? Analysis of 1736 hepatectomies performed over 3 decades in a single center.

INTRODUCTION: Surgery is the only potentially curative treatment for colorectal cancer liver metastases (CRLM) and its indication and results have varied in the last 30 years. METHODS: All patients operated on for CRLM in our centre from 1990 to 2021 were prospectively collected, establishing 3 subgroups based on the year of the first surgery: group A 1990-1999, group B 2000-2010, group C 2011-2021. Clinical characteristics and the results of survival, recurrence and prognostic factors were compared. RESULTS: 1736 hepatectomies were included (Group A n = 208; Group B n = 770; Group C n = 758). Patients in group C had better survival at 5 and 10 years (A 40.5%/28.2%; B 45.9%/32.2%; C 51.6%/33.1%, p = 0.013), although there were no differences between groups in overall recurrence at 5 and 10 years (A 73%/75.7%; B 67.6%/69.2%, and C 63.9%/66%, p = 0.524), nor in liver recurrence (A 46.4%/48.2%; B 45.8%/48.2%; and C 44.4%/48.4%, p = 0.899). An improvement was observed in median survival after recurrence, being 19 months, 23 months, and 31 months (groups A, B and C respectively). Prognostic factors of long-term survival changed over the 3 study periods. The only ones that remained relevant in the last decade were the presence of >4 liver metastasis, extrahepatic disease at the time of hepatectomy, and intraoperative blood transfusion. CONCLUSIONS: Survival after surgery for CRLM has improved significantly, although this cannot be explained by a reduction in overall and hepatic recurrence, but rather by an improvement in post-recurrence survival. Involvement of the resection margin has lost prognostic value in the last decade.

Primary gastric squamous cell carcinoma: case report.

Primary gastric squamous cell carcinoma is an extremely rare entity with an unknown etiopathology, and prognosis is generally poor. While diagnostic criteria are standardized, the optimal treatment strategy is not defined due to its rarity. In this article, we present a case of primary gastric squamous cell carcinoma, discussing its approach and treatment.

Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain.

PURPOSE: Clinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers. METHODS: Multicenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages. RESULTS: Three hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy. CONCLUSION: Our study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved. TRIAL REGISTRATION: Not applicable.

Development and validation of the PERCEPT-PREVENT tool to determine risk perception and attitudes towards digestive cancer screening.

BACKGROUND AND AIMS: Colorectal cancer (CRC) screening is recommended worldwide, while gastric cancer (GC) screening may also be defendable in some settings. However, adherence rates and factors influencing participation are not well characterized. This study aimed to validate a tool to determine risk perception of CRC and GC and also of endoscopy-related complications. METHODS: A questionnaire in CRC risk perception based on the Health Belief Model was used. Forward/backward translation (English-Portuguese) and cultural adaptation were performed. After revision by a panel of experts, the questionnaire was adapted to target GC risk perception and perceptions towards endoscopy-related complications. The final version of the questionnaire (PERCEPT-PREVENT tool) was applied to 44 individuals, through telephonic interview, at enrolment and at intervals ≤3 weeks. Test-retest reliability and agreement were assessed. RESULTS: Almost perfect reliability between test and retest was obtained for CRC symptom knowledge score (ICC = 0.88), risk factor knowledge score (ICC = 0.89), and perceived severity (ICC = 0.84). At least moderate agreement between test and retest was obtained for GC symptom knowledge score (ICC = 0.94), risk factor knowledge score (ICC = 0.92), and perceived severity (ICC = 0.58). Test-retest reliability was assessed for barrier domains [faecal occult blood test ICC = 0.63; colonoscopy ICC = 0.79; upper GI endoscopy (UGIE) ICC = 0.83]. A total of 91% and 98% of participants gave the same answer in the test and retest for preferred method of CRC screening and intention to undergo UGIE for GC screening combined with a screening colonoscopy, respectively. DISCUSSION: PERCEPT-PREVENT is a valid and reliable tool for CRC and GC risk perception evaluation.

Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles.

Introduction: Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. Methods: The candidate biomarkers were tested in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and their diagnostic potential was evaluated in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients' plasma and urinary EVs. Next, the results were validated in an independent cohort of plasma EVs from 31 PCa and 31 BPH patients. Results: We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p < 0.0001) tRF-Lys-CTT-5c (p < 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p < 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers-GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively, in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in the blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. Conclusion: This study identified two novel EV-enclosed RNA biomarkers-NKX3-1 and GLO1-for the detection of PCa, and highlights the complementary nature of GLO1, NKX3-1 and PSA as combined biomarkers in liquid biopsies of PCa.

Validation of the Portuguese version of the supportive care needs survey short-form questionnaire (SCNS-SF34-Pt) and the breast cancer supplementary module (SCNS-BR8-Pt).

OBJECTIVE: This study aimed to test the psychometric properties of the Portuguese Supportive Care Needs Survey-Short Form-34 (SCNS-SF34-Pt) and its breast cancer-specific complementary module (SCNS-BR8-Pt). A further aim was to characterize Portuguese Breast Cancer Survivors' (BCS) unmet supportive care needs, using these measures. METHODS: A convenient sample of BCS was recruited from five hospitals in Portugal and invited to complete SCNS-SF34-Pt and SCNS-BR8-Pt, EORTCQLQC30 and QLQBR23, the Generalized Anxiety Disorder, and the Patient Health-Questionnaire. The validity (i.e. convergent, discriminant and convergent validity) and reliability of SCNS-SF34-Pt and SCNS-BR8-Pt were statistically evaluated. BCS' unmet supportive care needs were descriptively assessed. FINDINGS: 336 BCS participated in the study. A four-factor solution was produced for SCNS-SF34-Pt. This solution included the Physical and daily living needs, Psychological needs, Sexuality needs, and Health system, information, and patient support needs dimensions (73% of the total variance; Cronbach's alpha=.82 to .97). SCNS-SF34-Pt demonstrated good convergent validity. It could also discriminate between known-groups regarding age, disease staging, treatment performed, and ECOG performance status. SCNS-BR8-Pt revealed a single-factor structure (62% of the total variance; Cronbach's alpha=.91).Portuguese BCS' most prevalent unmet supportive care needs were associated with the Psychological, and Physical and daily living domains. Fear of cancer spreading, the inability to do things as usual, and lack of energy/tiredness were perceived as issues requiring further supportive care. CONCLUSIONS: SCNS-SF34-Pt and the SCNS-BR8-Pt are valid and reliable tools to assess Portuguese BCS' unmet supportive care needs. Fear of cancer spreading and lack of energy/tiredness concerns should be a target of supportive care services.

IκB kinase-α coordinates BRD4 and JAK/STAT signaling to subvert DNA damage-based anticancer therapy.

Activation of the IκB kinase (IKK) complex has recurrently been linked to colorectal cancer (CRC) initiation and progression. However, identification of downstream effectors other than NF-κB has remained elusive. Here, analysis of IKK-dependent substrates in CRC cells after UV treatment revealed that phosphorylation of BRD4 by IKK-α is required for its chromatin-binding at target genes upon DNA damage. Moreover, IKK-α induces the NF-κB-dependent transcription of the cytokine LIF, leading to STAT3 activation, association with BRD4 and recruitment to specific target genes. IKK-α abrogation results in defective BRD4 and STAT3 functions and consequently irreparable DNA damage and apoptotic cell death upon different stimuli. Simultaneous inhibition of BRAF-dependent IKK-α activity, BRD4, and the JAK/STAT pathway enhanced the therapeutic potential of 5-fluorouracil combined with irinotecan in CRC cells and is curative in a chemotherapy-resistant xenograft model. Finally, coordinated expression of LIF and IKK-α is a poor prognosis marker for CRC patients. Our data uncover a functional link between IKK-α, BRD4, and JAK/STAT signaling with clinical relevance.

Factors associated with the time to treat breast cancer in the pandemic period: an observational study.

OBJECTIVES: to analyze the factors associated with the time to surgical treatment for breast cancer in patients seen at a reference mastology outpatient clinic in the State of Ceará. METHODS: analytical, longitudinal study with medical charts from the Mastology Outpatient Clinic of Assis Chateaubriand Maternity School. We used 140 medical charts of breast cancer patients with surgeries performed during the pandemic. RESULTS: the study evidenced associations between schooling and shorter time to treatment in patients who underwent biopsy before the first outpatient visit (p = 0.026; OR: 0.16; CI = 0.03-0.85); in the group who had the biopsy performed by the outpatient clinic, was associated the type of tumor (p = 0.019) and neoadjuvant therapy (p = 0.000). CONCLUSIONS: the lesser educational level, tumor type, and use of neoadjuvant therapy were factors associated with the time to treatment during the pandemic period.

Is dyslipidemia a risk factor for trastuzumab-induced cardiotoxicity in breast cancer patients? A systematic review and meta-analysis.

INTRODUCTION: Breast cancer patients undergoing trastuzumab therapy have greater risk of cardiovascular disease. Risk factors for this effect have been proposed. However, the role of dyslipidemia is not completely understood. This systematic review aimed to explore the role of dyslipidemia in trastuzumab-induced cardiotoxicity. METHODS: The investigators searched MEDLINE, Scopus, and Web of Science up to October 25, 2020. A random-effects model was used to determine pooled estimates of the results. The primary endpoint was trastuzumab-induced cardiotoxicity in patients with and without dyslipidemia. RESULTS: A total of 39 studies were selected for inclusion in our systematic review assessing 21079 patients. One study demonstrated a statistically significant association between dyslipidemia and cardiotoxicity (OR=2.28, 95% CI 1.22-4.26, p=0.01). In all other studies, no such association was observed. Twenty-one studies including 6135 patients were eligible for meta-analysis. In this meta-analysis of unadjusted data, dyslipidemia was significantly associated with cardiotoxicity (OR=1.25, 95% CI 1.01-1.53, p=0.04, I2=0%), however, a subgroup analysis of studies reporting adjusted measures did not demonstrate a significant association (OR=0.89, 95% CI 0.73-1.10, p=0.28, I2=0%). CONCLUSION: This systematic review and meta-analysis did not demonstrate a significant association between dyslipidemia alone and the development of cardiotoxicity. In the absence of other relevant cardiovascular risk factors, review of lipid profile may not be obligatory, and management of patients could be performed without referral for cardio-oncology assessment. Further investigation of risk factors for trastuzumab-induced cardiotoxicity is required to confirm these results.

Preoperative staging of uterine cancer: can transvaginal ultrasonography play a role?

Introduction: Preoperative staging of uterine cancer has recently been implied as an important contribution to an accurate selection of low-risk cases, ultimately avoiding unnecessary lymph node debulking. The aim of this study was to evaluate the validity of transvaginal ultrasonography (TVS) in preoperative staging of uterine cancer in comparison to pelvic magnetic resonance imaging (MRI) and permanent section. Methods: We conducted a prospective longitudinal multicenter trial between 2017 and 2018. Inclusion criteria comprised cases of endometrial neoplasia histologically confirmed or strong imaging suspicion, candidates for elective surgery as primary treatment. Proportions of Agreement (PA), kappa statistic (K), sensitivity, specificity and accuracy were calculated with 95% confidence intervals (95%CI). Results: Eighty-two patients were eligible for the study, presenting a mean age of 68 years (standard deviation 11). In what concerns the TVS evaluation of myometrial invasion, the subjective and objective methods of Gordon and Karlsson presented a sensitivity of 79%, 79% and 67% [95%CI 63-91; 63-91; 50-81], a specificity of 65%, 58% and 79% [95%CI 49-79; 42-73; 64-89] and an overall accuracy of 72%, 68% and 73% [95%CI 61-81; 57-78; 63-82]. MRI presented respectively a sensitivity, specificity and overall accuracy of 92%, 70% and 82% [95%CI 77-98; 52-85; 71-90]. Regarding cervical involvement, the sensitivity was respectively 31%, 50% and 67% [95%CI 9-61; 21-79; 35-90] for the subjective method, objective TVS and MRI, and the specificity was 98%, 90% and 100% [95%CI 92-100; 77-97; 94;100]. Agreement between TVS and MRI was superior in the assessment of cervical invasion, with PA ranging from 0.82 to 0.93 and K from 0.45 to 0.58, in comparison to myometrial invasion with PA ranging from 0.68 to 0.73 and K from 0.31 to 0.50. Considering the assessment of cervical involvement, as MRI showed a specificity of 100% it is not possible to increase the specificity. However, it was possible to increase the sensitivity, considering the combination of TVS with objective approach and MRI. Conclusion: TVS may have a promising role as a tool for preoperative staging of endometrial carcinoma, presenting a performance that approximates to MRI, with a higher agreement in the assessment of cervical invasion.

Identification of a Twelve-microRNA Signature with Prognostic Value in Stage II Microsatellite Stable Colon Cancer.

We aimed to identify and validate a set of miRNAs that could serve as a prognostic signature useful to determine the recurrence risk for patients with COAD. Small RNAs from tumors of 100 stage II, untreated, MSS colon cancer patients were sequenced for the discovery step. For this purpose, we built an miRNA score using an elastic net Cox regression model based on the disease-free survival status. Patients were grouped into high or low recurrence risk categories based on the median value of the score. We then validated these results in an independent sample of stage II microsatellite stable tumor tissues, with a hazard ratio of 3.24, (CI95% = 1.05-10.0) and a 10-year area under the receiver operating characteristic curve of 0.67. Functional analysis of the miRNAs present in the signature identified key pathways in cancer progression. In conclusion, the proposed signature of 12 miRNAs can contribute to improving the prediction of disease relapse in patients with stage II MSS colorectal cancer, and might be useful in deciding which patients may benefit from adjuvant chemotherapy.

Breast Cancer Survivors' Attitudes toward eMental Health: A Cross-Sectional Study.

BACKGROUND: Breast cancer survivors' (BCS) attitudes toward eMental Health (eMH) are largely unknown, and adoption predictors and their interrelationships remain unclear. This study aimed to explore BCS' attitudes toward eMH and investigate associated variables. METHODS: A cross-sectional study involving 336 Portuguese BCS was conducted. Attitudes toward eMH, depression and anxiety symptoms, health-related quality of life, and sociodemographic, clinical, and internet-related variables were assessed using validated questionnaires. Spearman-ranked correlations, χ2, and multiple regression analyses were computed to explore associations between attitudes and collected variables. RESULTS: BCS held a neutral stance toward eMH. In models adjusted for age and education, positive attitudes were statistically significantly associated with increased depressive symptoms and worse emotional, cognitive, and body image functioning. Social network use, online health information and mental healthcare seeking, higher self-reported knowledge of eMH, and previous use of remote healthcare were positively associated with better attitudes toward eMH. CONCLUSIONS: eMH programs targeting BCS seem to be a promising strategy for providing supportive psychosocial care to BCS. However, increasing awareness about eMH efficacy and security may be necessary to improve its acceptance and use among BCS. Additional research is necessary to understand how BCS' unmet care needs, and specifically their psychological distress severity, may impact BCS' acceptance and use of eMH.

Minimally invasive surgery for pilonidal disease: Outcomes of the Gips technique-A systematic review and meta-analysis.

BACKGROUND: Pilonidal disease is a common inflammatory condition that significantly impacts quality of life. Currently, there is a tendency to favor minimally invasive procedures. The present review aims to summarize the evidence and assess the outcomes of the Gips procedure. METHODS: A systematic review was conducted on MEDLINE/Pubmed, Scopus, Web of Science, and Cochrane Library databases until December 2022. Eligible studies included patients with pilonidal disease submitted to the Gips procedure, reporting at least 1 of the following outcomes: wound complications, wound healing time, time to resume daily activities, and recurrence (International Prospective Register of Systematic Reviews protocol: CRD42023389269). The National Institutes of Health assessment tool was used for risk of bias evaluation. Meta-analysis was performed using OpenMeta[Analyst] and R software, and a subgroup analysis was performed when applicable. RESULTS: Thirteen observational studies with a total of 4,286 patients submitted to Gips were included. The pooled wound complications rate was 7.8% (95% confidence interval: 5.1-10.6), the median time to resume daily activities was 1 day (95% confidence interval: 1-2), and the mean wound healing time was 4.7 weeks (95% confidence interval: 3.0-6.4). Subgroup analysis showed that pooled recurrence rate was 6.5% (95% confidence interval: 5.2-7.8) up to 2 years and 38.9% (95% confidence interval: 27.1-50.7) after more than 2 years of surgery. Most results showed substantial heterogeneity across studies. CONCLUSION: Despite apparent favorable outcomes of the Gips procedure, there is a high recurrence rate over time. Because included studies had an observational nature and unstandardized methodologies, comparative randomized controlled trials with longer follow-ups are needed for high-level evidence regarding these outcomes.

A Smartphone-Delivered Program (Anathema) to Promote the Sexual Health of Older Adults, Colorectal Cancer Survivors, and Stroke Survivors: Protocol for a Feasibility Pilot Randomized Controlled Trial.

BACKGROUND: Despite the prevalence of sexual distress and dysfunction in older adults in general and stroke and colorectal cancer survivors in particular, access to specialized care is limited by organizational barriers and stigma, embarrassment, and discrimination. The internet allows reaching services that would otherwise be difficult or impossible to reach, and as smartphones are personal (intimate) technologies, they are a promising vehicle to close this gap. However, research focusing on smartphone-delivered sexual health promotion programs is scarce. OBJECTIVE: This study aims to assess the acceptability, feasibility, and preliminary efficacy of Anathema, an 8-week, iOS/Android smartphone-delivered, individually tailored, cognitive-behavioral sexual health promotion program developed to improve relationship and sexual satisfaction, sexual functioning, sexual distress, sexual pleasure, and health-related quality of life (HRQoL) in older adults, colorectal cancer survivors, and stroke survivors compared to treatment as usual in a waiting-list control condition. METHODS: Two-arm, parallel, open-label, waiting list, feasibility, pilot randomized controlled trials (RCTs) will be conducted involving older adults, stroke survivors, and colorectal cancer survivors. The primary outcomes are the acceptability, usability, and feasibility of Anathema. Sexual function, relationship and sexual satisfaction, sexual pleasure, sexual distress, anxiety, depression, and HRQoL are the secondary outcomes. This study has been reviewed and approved by the ethics committees of Instituto Português de Oncologia do Porto Francisco Gentil, Europacolon Portugal, Faculty of Psychology and Educational Sciences, University of Porto, and Sigmund Freud University (approval numbers: CES218R/021, CES19/023, and 2022/01-05b). RESULTS: This project is funded by the European Commission through the Active and Assisted Living (AAL) Programme (reference: AAL-2020-7-133-CP) from April 2021 to December 2023. Recruitment for the pilot RCTs started on January 2023 in Portugal, Austria, and the Netherlands and is currently ongoing. As of May 2023, we randomized 49 participants in the trials. We expect to complete the RCTs in September 2023. The results on the acceptability, feasibility, and preliminary efficacy of Anathema are expected in the second semester of 2023. We expect Anathema to be highly accepted by the populations under study; to prove feasible to scale up to parent RCTs; and to be potentially efficacious in improving sexual functioning, relationship and sexual satisfaction, sexual distress, sexual pleasure, and HRQoL in older adults, colorectal cancer survivors, and stroke survivors compared to treatment as usual in a waiting-list control condition. The study results will be published in open-access venues according to COREQ (Consolidated Criteria for Reporting Qualitative Research) and CONSORT EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) guidelines. CONCLUSIONS: The study results will inform the refinement and scale-up of Anathema. Anathema's wider-scale implementation can potentially promote the sexual health of largely neglected user groups such as older adults, colorectal cancer survivors, and stroke survivors. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46734.

Health-related quality of life of women with breast cancer being treated with hormone therapy: A scoping review.

OBJECTIVE: To map the evidence available in the literature on the health-related quality of life of women with breast cancer using hormone therapy. DATA SOURCES: This review followed the Joanna Briggs Institute methodological recommendations and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews reporting guidelines. Searches were performed in nine databases using descriptors, synonyms and keywords; grey literature was also included. The review protocol was registered with the Open Science Framework under doi: http://doi.org/10.17605/OSF.IO/347FM. Inclusion criteria were established according to the Population, Concept, and Context strategy. The selection of studies was performed by two independent reviewers with the aid of RAYYAN software and disagreements were resolved by a third reviewer. The main information from the included articles was grouped into textual categories and presented by means of a narrative synthesis. DATA SUMMARY: A total of 5419 records were identified, of which 42 studies fully met the eligibility criteria. Most were multicenter studies (42.9%) and randomized controlled trials (62%). Most studies addressed anastrozole (39.5%), letrozole (34.2%), and tamoxifen (26.3%), which were studied alone or in combination. The most widely used health-related quality-of-life assessment tool was the EORTC-QLQ-C30. The concomitant use of hormone therapy and cyclin-dependent kinase inhibitors 4 and 6 showed improvement in health-related quality of life. CONCLUSION: In recent years there has been an increase in studies focused on health-related quality of life, and the evidence pointed to relevant information on health-related quality of life and the use of endocrine therapy, tamoxifen in combination with aromatase inhibitors, as well as aromatase inhibitor alone and the use of cyclin-dependent kinase 4 and 6.