Bone Metastases Detection in Patients with Breast Cancer: Does Bone Scintigraphy Add Information to PET/CT?

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has become in recent years a tool for breast cancer (BC) staging. However, its accuracy to detect bone metastases is classically considered inferior to bone scintigraphy (BS). The purpose of this work is to compare the effectiveness of bone metastases detection between PET/CT and BS. MATERIALS AND METHODS: Prospective study of 410 female patients treated in a Comprehensive Cancer Center between 2014 and 2020 that performed PET/CT and BS for staging purposes. The image analysis was performed by 2 senior nuclear medicine physicians. The comparison was performed based on accuracy, sensitivity, and specificity on a patient and anatomical region level and was assessed using McNemar's Test. An average ROC was calculated for the anatomical region analysis. RESULTS: PET/CT presented higher values of accuracy and sensitivity (98.0% and 93.83%), surpassing BS (95.61% and 81.48%) in detecting bone disease. There was a significant difference in favor of PET/CT (sensitivity 93.83% vs. 81.48%), however, there is no significant difference in eliminating false positives (specificity 99.09% vs. 99.09%). PET/CT presented the highest accuracy and sensitivity values for most of the bone segments, only surpassed by BS for the cranium. There was a significant difference in favor of PET/CT in the upper limb, spine, thorax (sternum) and lower limb (pelvis and sacrum), and in favor of BS in the cranium. The ROC showed that PET/CT has a higher sensitivity and consistency across the bone segments. CONCLUSION: With the correct imaging protocol, PET/CT does not require BS for patients with BC staging.

Quality of Life in Male Breast Cancer: Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG).

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program. METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons. RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease. CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.

Altered IgG glycosylation at COVID-19 diagnosis predicts disease severity.

The nature of the immune responses associated with COVID-19 pathogenesis and disease severity, as well as the breadth of vaccine coverage and duration of immunity, is still unclear. Given the unpredictability for developing a severe/complicated disease, there is an urgent need in the field for predictive biomarkers of COVID-19. We have analyzed IgG Fc N-glycan traits of 82 SARS-CoV-2+ unvaccinated patients, at diagnosis, by nano-LC-ESI-MS. We determined the impact of IgG Fc glyco-variations in the induction of NK cells activation, further evaluating the association between IgG Fc N-glycans and disease severity/prognosis. We found that SARS-CoV-2+ individuals display, at diagnosis, variations in the glycans composition of circulating IgGs. Importantly, levels of galactose and sialic acid structures on IgGs are able to predict the development of a poor COVID-19 disease. Mechanistically, we demonstrated that a deficiency on galactose structures on IgG Fc in COVID-19 patients appears to induce NK cells activation associated with increased release of IFN-γ and TNF-α, which indicates the presence of pro-inflammatory immunoglobulins and higher immune activation, associated with a poor disease course. This study brings to light a novel blood biomarker based on IgG Fc glycome composition with capacity to stratify patients at diagnosis.

SARS-CoV-2 Infection Drives a Glycan Switch of Peripheral T Cells at Diagnosis.

COVID-19 is a highly selective disease in which SARS-CoV-2 infection can result in different clinical manifestations ranging from asymptomatic/mild to severe disease that requires hospitalization. In this study, we demonstrated that SARS-CoV-2 infection results in a glycosylation reprogramming of circulating lymphocytes at diagnosis. We identified a specific glycosignature of T cells, defined upon SARS-CoV-2 infection and apparently triggered by a serological factor. This specific glycan switch of T cells is detected at diagnosis being more pronounced in asymptomatic patients. We further demonstrated that asymptomatic patients display an increased expression of a viral-sensing receptor through the upregulation of DC-SIGN in monocytes. We showed that higher levels of DC-SIGN in monocytes at diagnosis correlates with better COVID-19 prognosis. This new evidence pave the way to the identification of a novel glycan-based response in T cells that may confer protection against SARS-CoV-2 infection in asymptomatic patients, highlighting a novel prognostic biomarker and potential therapeutic target.

Patient perspectives on repeated contrast-enhanced mammography and magnetic resonance during neoadjuvant chemotherapy of breast cancer.

BACKGROUND: The burden perceived by the patient of repeated imaging required for neoadjuvant chemotherapy (NAC) monitoring warrants attention due to the increased use of NAC and imaging. PURPOSE: To evaluate and compare the experienced burden associated with repeated contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) during NAC for breast cancer from the patient perspective. MATERIAL AND METHODS: Approval from the ethics committee and written informed consent were obtained. In this prospective study, CEM and MRI were performed on 38 patients with breast cancer before, during, and after NAC in a tertiary cancer center. The experienced burden was evaluated with a self-reported questionnaire addressing duration, comfort, anxiety, positioning, and intravenous contrast administration, each measured on a 5-point Likert scale. The participants were asked their preference between CEM or MRI. Statistical comparisons were performed and P<0.05 was considered significant. RESULTS: Most participants (n = 29, 76%) preferred CEM over MRI (P = 0.0008). CEM was associated with a significantly shorter duration (P < 0.001), greater overall comfort (P < 0.01), more comfortable positioning (P = 0.01), and lower anxiety (P = 0.03). Intravenous contrast administration perception revealed no significant difference. Only 4 (10%) participants preferred MRI over CEM, due to the absence of breast compression. CONCLUSION: In the hypothetical scenario of equal diagnostic accuracy, most participants preferred CEM and compared CEM favorably to MRI in all investigated features at repeated imaging required for NAC response assessment. Our results indicate that repeated examinations with CEM is well tolerated and constitutes a patient-friendly alternative for NAC imaging monitoring in breast cancer.

Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

BACKGROUND: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. LAY SUMMARY: Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.

Composition of the immunoglobulin G glycome associates with the severity of COVID-19.

A large variation in the severity of disease symptoms is one of the key open questions in coronavirus disease 2019 (COVID-19) pandemics. The fact that only a small subset of people infected with severe acute respiratory syndrome coronavirus 2 develops severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the immunoglobulin G (IgG) glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of interindividual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

SARS-CoV-2 infection in kidney transplant recipients: Early report of five cases.

From December 2019 to March 2020, China was the epicenter of the SARS-CoV-2 infection pandemic, but from that moment on, Europe surpassed China in the number of new cases and deaths related to this novel viral respiratory infection. The emergence of this world pandemic is particularly important for solid organ transplant recipients, who might have an increased risk of mortality, not only due to their chronic immunosuppression status, but also to the cardiovascular risk that correlates with several years of chronic kidney disease. To the extent that there is still a lack of knowledge about the clinical characteristics, evolution, and prognosis of SARS-CoV-2 infection in kidney transplant recipients, we will report the first 5 cases diagnosed and followed in our transplant unit, as well as share the therapeutic strategies adopted.

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer.

The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment.

Leprosy presenting as remitting seronegative symmetrical synovitis with pitting oedema syndrome - a case report.

BACKGROUND: Leprosy typically manifests with skin and peripheral nerve involvement. Musculoskeletal complaints are the third most common, and can be the sole presenting manifestation. They range from arthralgia/arthritis in reactional states to full mimics of systemic rheumatic diseases. Remitting Seronegative Symmetrical Synovitis with Pitting Oedema syndrome has only been described once in a patient with already diagnosed Leprosy. CASE REPORT: A 68-year-old male, from an endemic region of familial amyloid polyneuropathy, presented with an inaugural Remitting Seronegative Symmetrical Synovitis with Pitting Oedema like syndrome, more that 20 years after travelling to Leprosy endemic areas. Arthritis would resurface whenever oral prednisone was tapered, so methotrexate was started, controlling the complaints. Only one year later, after the appearance of peripheral neuropathy and skin lesions, it was possible to diagnose Leprosy, through the identification of Mycobacterium leprae bacilli in a peripheral nerve biopsy. CONCLUSION: This report is an example of the heterogeneity of manifestations of Leprosy, namely rheumatic, and the challenge of diagnosing it when typical complaints are absent. It is also a reminder that this disease should be considered whenever a patient with a combination of skin/neurologic/rheumatic complaints has travelled to endemic countries in the past.

Is Routine Urinary Screening Indicated Prior To Elective Total Joint Arthroplasty? A Systematic Review and Meta-Analysis.

BACKGROUND: Prosthetic joint infection (PJI) is a serious complication after total joint arthroplasty, and prevention is of great importance. The genitourinary tract is a potential source of bacterial seeding and one that can be easily managed. Despite little supportive evidence, routine urine screening and subsequent treatment before elective surgery in patients without symptoms has found its way into clinical practice in many countries. This systematic review and meta-analysis aims to ascertain whether asymptomatic bacteriuria (ASB) is a risk factor for PJI and if so, whether preoperative antibiotic treatment is effective in reducing its risk. METHODS: PubMed, Ovid Medline, and Cochrane databases were searched using a systematic strategy. Selection of papers was exclusive to include only those which offered information about PJI rate specifically in patients with or without asymptomatic abnormal urinalysis or bacteriuria and/or information on whether ASB patients were preoperatively treated with antibiotics or not to be included in the analysis. RESULTS: Six-hundred sixty-three papers were screened, and 10 papers were ultimately included (28,588 patients). Results show an increased risk of developing PJI among ASB patients (odds ratio = 3.64, 95% confidence interval = 1.40-9.42). However, most PJI microorganisms are unrelated to those previously found in the urine and preoperative antibiotic therapy does not influence PJI risk (odds ratio = 0.98, 95% confidence interval = 0.39-2.44). CONCLUSION: Routine urinary screening prior to elective total joint arthroplasty and treatment of asymptomatic patients is not recommended.

Spatial requirement for PAMO for transformation of non-native linear substrates.

Phenylacetone monooxygenase is the most stable and thermo-tolerant member of the Baeyer-Villiger monooxygenases family, and therefore it is an ideal candidate for the synthesis of industrially relevant ester or lactone compounds. However, its limited substrate scope has largely limited its industrial applications. Linear substrates are interesting from an industrial point of view, it is thus necessary to identify the essential spatial requirement for achieving high conversions for non-native linear substrates. Here using molecular dynamics simulations, we compared the conversion of a non-native linear substrate 2-octanone and the native substrate phenylacetone, catalyzed by the WT enzyme and a quadruple variant P253F/G254A/R258M/L443F that exhibits significantly improved activity towards 2-octanone. We uncovered that a remarkable movement of L289 is crucial for a reshaping of the active site of the quadruple variant so as to prevent the aliphatic substrate from moving away from the C4a-peroxyflavin, thus enabling it to keep a catalytically relevant pose during the oxygenation process. By performing steady-state kinetic analysis of two single-mutation variants at position 258, we further validated that the L289 reposition is attributed to the combined effect of quadruple mutations. In order to further explore the substrate scope of PAMO we also studied the binding of cyclopentanone and 2-phenylcyclohexanone, which are the typical substrates of CPMO in group I and CHMO in group III, respectively. Our study provides fundamental atomic-level insights in rational engineering of PAMO for wide applications in industrial biocatalysis, in particular, in the biotransformation of long-chain aliphatic oils into potential biodiesels.

Catalytic mechanism of phenylacetone monooxygenases for non-native linear substrates.

Phenylacetone monooxygenase (PAMO) is the most stable and thermo-tolerant member of the Baeyer-Villiger monooxygenase family, and therefore it is an ideal candidate for the synthesis of industrially relevant compounds. However, its limited substrate scope has largely limited its industrial applications. In the present work, we provide, for the first time, the catalytic mechanism of PAMO for the native substrate phenylacetone as well as for a linear non-native substrate 2-octanone, using molecular dynamics simulations, quantum mechanics and quantum mechanics/molecular mechanics calculations. We provide a theoretical basis for the preference of the enzyme for the native aromatic substrate over non-native linear substrates. Our study provides fundamental atomic-level insights that can be employed in the rational engineering of PAMO for wide applications in industrial biocatalysis, in particular, in the biotransformation of long-chain aliphatic oils into potential biodiesels.

Patterns of recurrence and treatment in male breast cancer: A clue to prognosis?

Male breast cancer (MBC) patients seem to have inferior survival compared to female (FBC) ones, which is not fully explained by usual prognostic factors. Recurrence analysis could show differences in relapse patterns and/or in patients' approaches that justify these outcomes. Retrospective analysis of MBC patients treated in a cancer center between 1990 and 2014, looking for relapse. For each patient, three matched FBC patients were selected by: diagnosis' year, age (within 5 years), stage and tumors' type (only luminal-like were considered). Differences between cohorts were assessed by χ(2) test and hierarchical clustering was performed to define subgroups according to relapse local. Survival curves were calculated by Kaplan-Meier and compared using log-rank test. Statistical significance was defined as p < 0.05. Groups were balanced according to age, histological grade, stage, expression of hormonal receptors and adjuvant treatments. Median time to recurrence was equivalent, p = 0.72, with the majority of patients presented with distant metastases, p = 0.69, with more lung involvement in male, p = 0.003. Male patients were more often proposed to symptomatic treatment (21.1% vs. 4.4%, p = 0.02). Overall and from recurrence survivals were poorer for male, median: 5 years [95% confidence interval (CI): 4.1-5.9 years] and 1 year (95% CI: 0-2.1 years) vs. 10 years (95% CI: 7.8-12.2 years) and 2 years (95% CI: 1.6-2.4 years), p < 0.001 and p = 0.004, respectively, and this tendency remained in the five cluster subgroups, that identified five patterns of relapse, p = 0.003. MBC patients had the worst survival, even after controlling important factors, namely the local of relapse. Palliative systemic treatment had favorable impact in prognosis and its frequently avoidance in male could justify the outcomes differences.

Deciphering the Molecular Mechanisms behind Drug Resistance in Ovarian Cancer to Unlock Efficient Treatment Options.

Ovarian cancer is a highly lethal form of gynecological cancer. This disease often goes undetected until advanced stages, resulting in high morbidity and mortality rates. Unfortunately, many patients experience relapse and succumb to the disease due to the emergence of drug resistance that significantly limits the effectiveness of currently available oncological treatments. Here, we discuss the molecular mechanisms responsible for resistance to carboplatin, paclitaxel, polyadenosine diphosphate ribose polymerase inhibitors, and bevacizumab in ovarian cancer. We present a detailed analysis of the most extensively investigated resistance mechanisms, including drug inactivation, drug target alterations, enhanced drug efflux pumps, increased DNA damage repair capacity, and reduced drug absorption/accumulation. The in-depth understanding of the molecular mechanisms associated with drug resistance is crucial to unveil new biomarkers capable of predicting and monitoring the kinetics during disease progression and discovering new therapeutic targets.

Long-term patient-reported outcomes from monarchE: Abemaciclib plus endocrine therapy as adjuvant therapy for HR+, HER2-, node-positive, high-risk, early breast cancer.

BACKGROUND: In monarchE, abemaciclib demonstrated a sustained benefit in invasive disease-free survival and a tolerable safety profile at 42-months median follow-up. With no expected disease-related symptoms, therapies in the adjuvant setting should preserve quality of life (QoL). With all patients off abemaciclib, we report updated patient-reported outcomes (PROs) for the full 2-year treatment period and follow-up. METHODS: Patients completed PROs including FACT-B, FACT-ES, and FACIT-Fatigue at baseline, 3, 6, 12, 18, and 24 months during treatment, and 1, 6, and 12 months after treatment discontinuation. Mixed effects repeated measures model estimated changes from baseline within and between arms for QoL scales and individual items. Meaningful changes were prespecified and no statistical testing was performed. Frequencies of responses to items associated with relevant adverse events and treatment bother were summarized. RESULTS: At baseline, completion rates for PRO instruments were >96 %. Mean changes from baseline for all QoL scales were numerically similar within and between arms (ie, less than prespecified thresholds). The same was observed for all individual items, except diarrhea. Within abemaciclib arm, meaningful differences for diarrhea were observed at 3 and 6 months (mean increases of 1.19 and 1.03 points on 5-point scale, respectively). During treatment, most patients in both arms (69-78 %) reported being bothered "a little bit" or "not at all" by side effects. Overall, patterns for fatigue were similar between arms. During post-treatment follow-up, PROs in both arms were similar to baseline. CONCLUSION: PRO findings confirm a tolerable and reversible toxicity profile for abemaciclib. QoL was preserved with the addition of adjuvant abemaciclib to endocrine therapy, supporting its use in patients with HR+, HER2-, high-risk early breast cancer.

Treatment of Psoriasis Patients with Latent Tuberculosis Using IL-17 and IL-23 Inhibitors: A Retrospective, Multinational, Multicentre Study.

BACKGROUND: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation. OBJECTIVE: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis. METHODS: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded. RESULTS: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant). CONCLUSIONS: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.

Metastatic Cervical Cancer: A Case That Recalls the Importance of a Multidisciplinary Approach.

Cervical cancer is one of the most common neoplasms in women. Usually, this cancer is only symptomatic in advanced stages and is associated with a poor prognosis. We present the case of a 34-year-old woman with localized cervical cancer at diagnosis treated with surgery in 2011. Six years later, she presented recurrent disease with vaginal, pelvic, and lung metastases. Since then, the patient completed three lines of chemotherapy and a line of immunotherapy, and she was submitted to external radiotherapy and orthopedic surgery. Currently, the patient keeps regular follow-ups and maintains a good performance status. The treatment of recurrent cervical cancer remains a challenge, and the prognosis is poor. This case emphasized the importance of multidisciplinary discussion towards cases of locally advanced or metastatic cervical cancer, which may change this paradigm.