Microelimination of Hepatitis C in patients with substance use and dual disorders - a Portuguese study.

Chronic hepatitis C is a serious condition with relevant public health implications. In Portugal, the prevalence of detectable HCV antibodies is about 0,54%, with higher values in risk groups. Compared to the general population, the prevalence of HCV infection is higher in individuals with psychiatric disorders. There are no studies reporting the prevalence of HCV antibodies in Portuguese psychiatric patients, or in patients with substance use disorders.We carried an observational, prospective study during a period of one year, for patients followed at the Dual Pathology Outpatient and Inpatient Unity of the Coimbra Hospital and University Center, and patients were tested for HCV antibodies. Of 149 patients, 17.4% had positive HCV antibodies and 7.38% had detectable HCV RNA. Patients with confirmed CHC were mostly male inpatients, aged 50 to 59 years, and reported unprotected sex with more than one concurrent partner in the previous six months; their main psychiatric diagnosis was "Disorders due to use of multiple specified psychoactive substances, including medications".This study reports a very high prevalence of positive HCV antibodies and confirmed CHC in patients followed in the Dual Pathology Outpatient and Inpatient Unity. This prevalence is higher than in general Portuguese population.

Effectiveness of Photobiomodulation in Reducing Pain and Disability in Patients with Knee Osteoarthritis: A Systematic Review with Meta-Analysis.

OBJECTIVE: Photobiomodulation (PBM) is not implemented in routine clinical management for knee osteoarthritis. This study aims to systematically investigate the effects of PBM in patients with knee osteoarthritis, comparing to placebo to understand its true clinical effects. METHODS: PubMed, EMBASE, Web of Science, and Cochrane databases were searched up to October 2023. Randomized placebo-controlled trials applying PBM versus placebo were included. Study characteristics, intervention parameters, and patient-reported and physical examination outcome measures were collected. The risk of bias was judged using the Cochrane risk-of-bias tool for randomized trials (version 2) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to interpret certainty of results. RESULTS: Ten studies were included comprising 542 participants. All studies were judged with unclear to high risk of bias. Meta-analysis for pain at rest (6 studies) showed that PBM significantly reduced pain at rest as compared to placebo (-0.7 [95% CI = -1.1 to -0.2]), moderate effect, very low certainty of evidence, whereas for the Timed "Up & Go" Test (3 studies), no significant effect was detected. Statistically significantly within-group (PBM) mean improvement was detected for pain, Lequesne Index, and gait performance outcomes, but not always clinically relevant or significant when compared to placebo. CONCLUSION: PBM reduces pain intensity in patients with knee osteoarthritis and may improve disability. However, the very low certainty of evidence does not allow to recommend its isolated use but may be used to complement other widely recommended therapies. More rigorous clinical trials and the revision of the recommended dosage guidelines are warranted to increase the strength of evidence. IMPACT: The findings indicate that photobiomodulation can reduce pain and improve disability in patients with knee osteoarthritis. However, researchers should continue to investigate isolated photobiomodulation intervention versus placebo and extend the dosage guidelines to other types of light emitters.

Derotational high tibial osteotomy in cases of anterior knee pain and/or patellofemoral instability: a systematic review.

IMPORTANCE: Derotational high tibial osteotomy (HTO) is a surgical intervention for correcting rotational malalignments in the lower limb, which may contribute to anterior knee pain (AKP) and/or patellofemoral instability (PFI). This surgical technique is not yet widely implemented and requires a systematic evaluation of its outcomes. AIM: To assess the effectiveness of derotational HTO in correcting rotational malalignments of the lower limb in patients with AKP and/or PFI through radiological, clinical, and patient-reported outcome measures. EVIDENCE REVIEW: Searches were conducted in the PubMed, Embase, and Web of Science databases up to March 3, 2023, to identify studies utilizing derotational HTO in patients with AKP and/or PFI. The primary outcome measures of interest were measurements of lower limb angular correction. Other radiological, clinical, and patient-reported outcome measures were also analyzed. The risk of bias was judged with the RoBANS tool. FINDINGS: A total of 8 studies were included, comprising 215 patients (27.0 â€‹± â€‹3.9 years) and 245 knees. The most reported angle was tibial torsion (k â€‹= â€‹6 studies, n â€‹= â€‹173 knees), with a mean difference between postoperative and preoperative values (postsurgical correction) ranging from -37.8° to -10.8°. Patient-reported outcome measures showed significant improvements in the postoperative moment, exceeding the minimal clinically important difference in almost all cases, and with high patient satisfaction (93.6%). CONCLUSIONS AND RELEVANCE: Derotational HTO allows the correction of rotational malalignments of the lower limb (tibial torsion) and promotes patient satisfaction. LEVEL OF EVIDENCE: Level IV.

Derotational distal femoral osteotomy corrects excessive femoral anteversion in patients with patellofemoral instability: A systematic review.

PURPOSE: Patellofemoral instability (PFI) is a common condition that can be caused from multiple factors, including lower limb rotational malalignments. Determining precise criteria for performing corrective torsional osteotomy can be a daunting task due to the lack of consensus on normal and excessive values and the limited evidence-based data in the postoperative results. The purpose was to assess the clinical, functional and imaging outcomes following derotational distal femoral osteotomy (DDFO) in patients with PFI and/or anterior knee pain (AKP) associated with lower limb rotational malalignments. METHODS: Searches were conducted on PubMed, EMBASE and Web of Science databases up to October 2023. Studies reporting outcomes after DDFO in patients with PFI and/or AKP were eligible for the systematic review. The primary outcome was imaging metrics, especially femoral anteversion. Secondary outcomes included the patient-reported outcome measures (PROMs) (clinical and functional). Quantitative synthesis involved the use of weighted averages to calculate pre- to postoperative mean differences (MD) and compare them against the minimal clinically important difference (MCID). RESULTS: Ten studies (309 knees) were included with a mean follow-up of 36.1 ± 11.7 months. Imaging outcomes consistently indicated the correction of femoral anteversion (MD = -19.4 degrees, 95% confidence interval: -20.1 to -18.7) following DDFO. PROMs showed significant improvements in most studies, exceeding the MCID. Patient satisfaction with the DDFO was high (93.3%). CONCLUSIONS: The DDFO was an effective treatment option for correcting excessive femoral anteversion in patients with PFI associated with clinically relevant functional and clinical improvement and a high satisfaction rate. LEVEL OF EVIDENCE: Level IV, systematic review of level II-IV studies.

Meniscal extrusion in knees with and without osteoarticular pathology: A systematic review of normative values and cut-offs for diagnostic criteria.

BACKGROUND: Meniscus extrusion is crucial for the diagnosis and treatment of meniscal injury, but the literature on this topic has not yet been systematized. The purpose of this systematic review was to compare diagnostic methods and summarize the data of medial and lateral meniscal extrusion in knees with and without osteoarticular pathology. METHODS: This systematic review was conducted according to the PRISMA 2020 statement. Searches were conducted on PubMed, EMBASE and Cochrane databases to identify studies that measured meniscal extrusion using magnetic resonance imaging (MRI) or ultrasound (US). Meniscal extrusion data was summarized as weighted mean for medial and lateral meniscus, and stratified according to the method of measurement (MRI or US) and presence of knee osteoarticular pathology. RESULTS: A total of 26 studies were included in this review. Weighted mean values of meniscal extrusion were always higher for the medial than the lateral meniscus, regardless of the method of measurement. The medial meniscus extrusion was always higher in knees with osteoarticular pathology than those without. For the lateral meniscus extrusion, the mean values were higher in those knees without osteoarticular pathology. When classifying pathological meniscal extrusion with pre-defined cut-off values, the higher the cut-off used, the lower the percentage of knees classified as pathological meniscal extrusion. CONCLUSIONS: The medial meniscus presents on mean higher extrusion and extrusion is higher in knees with osteoarticular pathology. Based on summary data, the most suitable cut-offs for pathological meniscal extrusion for both MRI and US seem to fall within >2 and >3 mm.

The Role of Systemic Steroids in Sciatica Due to Herniated Lumbar Disc: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Evaluate the role of systemic steroids in treating patients with sciatica due to lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: The association between LDH and sciatica has been well described. The use of steroids seems logical in this context; however, their efficacy is not well described, and their use remains controversial. METHODS: A comprehensive search on PubMed, EMBASE, and Scopus databases (up to February 15, 2022) was performed to identify randomized clinical trials that included patients with symptoms of sciatica due to LDH that were treated with systemic steroids. The risk of bias was judged using the Cochrane risk-of-Bias2 tool. Meta-analysis was conducted using a random-effects model to estimate the between-group effect size for pain and functional outcomes. The risk of developing adverse events (AE) was computed using relative risks. All pooled results are reported with their 95% confidence interval (CI) and certainty of evidence analyzed using the Grading of Recommendations Assessment, Development, and Evaluation framework. RESULTS: Ten studies met inclusion criteria, comprising a total of 1017 participants: 540 in the treatment group and 477 in the control group. Steroid treatment was associated with a significant superior reduction of pain (SMD = -0.42, 95% CI -0.76 to -0.08, weak effect, very-low certainty) and reduction in disability (SMD = -0.30, 95% CI -0.51 to -0.10, weak effect, very-low certainty). Corticosteroid administration was associated with a significant increased risk of developing an AE (relative risks = 2.00, 95% CI 1.40 to 2.85, low certainty). CONCLUSION: The use of systemic steroids in the treatment of sciatica due to LDH seems reasonable despite a 2-fold higher risk of developing mild AEs. However, the effect size is small for reducing pain in the short term and improving functional outcomes at long-term follow-up.

Inconsistency in Shoulder Arthrometers for Measuring Glenohumeral Joint Laxity: A Systematic Review.

There is no consensus on how to measure shoulder joint laxity and results reported in the literature are not well systematized for the available shoulder arthrometer devices. This systematic review aims to summarize the results of currently available shoulder arthrometers for measuring glenohumeral laxity in individuals with healthy or injured shoulders. Searches were conducted on the PubMed, EMBASE, and Web of Science databases to identify studies that measure glenohumeral laxity with arthrometer-assisted assessment. The mean and standard deviations of the laxity measurement from each study were compared based on the type of population and arthrometer used. Data were organized according to the testing characteristics. A total of 23 studies were included and comprised 1162 shoulders. Populations were divided into 401 healthy individuals, 278 athletes with asymptomatic shoulder, and 134 individuals with symptomatic shoulder. Sensors were the most used method for measuring glenohumeral laxity and stiffness. Most arthrometers applied an external force to the humeral head or superior humerus by a manual-assisted mechanism. Glenohumeral laxity and stiffness were mostly assessed in the sagittal plane. There is substantial heterogeneity in glenohumeral laxity values that is mostly related to the arthrometer used and the testing conditions. This variability can lead to inconsistent results and influence the diagnosis and treatment decision-making.

Accuracy of Magnetic Resonance Imaging in the Diagnosis of Multiple Ligament Knee Injuries: A Multicenter Study of 178 Patients.

BACKGROUND: Magnetic resonance imaging (MRI) has shown limited diagnostic accuracy for multiple ligament knee injuries (MLKIs), especially posterolateral corner (PLC) injuries. HYPOTHESIS: The diagnostic accuracy of MRI for MLKIs will only be moderate for some knee structures. Patient-related factors and injury patterns could modify the diagnostic accuracy of MRI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All patients with MLKIs surgically treated between January 2014 and December 2020 in the centers participating in the study were reviewed. We recorded sex, age, mechanism of injury, time from injury to MRI, and vascular and neurological associated lesions. Lesions to the anterior cruciate ligament (ACL), posterior cruciate ligament, medial collateral ligament, lateral collateral ligament (LCL), popliteus tendon, popliteofibular ligament, iliotibial band, biceps tendon, medial and lateral meniscus, and articular cartilage from MRI reports and surgical records were also collected. The sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy, diagnostic odds ratio, positive and negative likelihood ratio, and intraclass correlation coefficient of MRI were calculated for each knee structure. With logistic regression, associations between patient and injury characteristics and MRI accuracy were assessed. RESULTS: A total of 178 patients (127 male; mean age, 33.1 years) were included. High-energy trauma was the most common mechanism of injury (50.6%), followed by sports trauma (38.8%) and low-energy trauma (8.4%). The ACL was the structure with the best diagnostic accuracy, diagnostic odds ratio, and positive predictive value (94.4%, 113.2, and 96.8%, respectively). PLC structures displayed the worst diagnostic accuracy among knee ligaments (popliteus tendon: 76.2%; LCL: 80.3%) and diagnostic odds ratio (popliteus tendon: 9.9; LCL: 17.0; popliteofibular ligament: 17.5). MRI was more reliable in detecting the absence of meniscal and chondral lesions than in identifying them. Logistic regression found that the diagnostic accuracy was affected by the Schenck classification, with higher Schenck grades having worse diagnostic accuracy for peripheral structures (iliotibial band, popliteus tendon, and biceps tendon) and improved diagnostic accuracy for the ACL and posterior cruciate ligament. CONCLUSION: The diagnostic accuracy of MRI for MLKIs largely varied among knee structures, with many of them at risk of a misdiagnosis, especially PLC, meniscal, and chondral lesions. The severity of MLKIs lowered the diagnostic accuracy of MRI for peripheral structures.

Effectiveness of Conservative Interventions After Acute Hamstrings Injuries in Athletes: A Living Systematic Review.

BACKGROUND: Hamstrings injuries are common in sports and the reinjury risk is high. Despite the extensive literature on hamstrings injuries, the effectiveness of the different conservative (i.e., non-surgical) interventions (i.e., modalities and doses) for the rehabilitation of athletes with acute hamstrings injuries is unclear. OBJECTIVE: We aimed to compare the effects of different conservative interventions in time to return to sport (TRTS) and/or time to return to full training (TRFT) and reinjury-related outcomes after acute hamstrings injuries in athletes. DATA SOURCES: We searched CINAHL, Cochrane Library, EMBASE, PubMed, Scopus, SPORTDiscus, and Web of Science databases up to 1 January, 2022, complemented with manual searches, prospective citation tracking, and consultation of external experts. ELIGIBILITY CRITERIA: The eligibility criteria were multi-arm studies (randomized and non-randomized) that compared conservative treatments of acute hamstrings injuries in athletes. DATA ANALYSIS: We summarized the characteristics of included studies and conservative interventions and analyzed data for main outcomes (TRTS, TRFT, and rate of reinjuries). The risk of bias was judged using the Cochrane tools. Quality and completeness of reporting of therapeutic exercise programs were appraised with the i-CONTENT tool and the certainty of evidence was judged using the GRADE framework. TRTS and TRFT were analyzed using mean differences and the risk of reinjury with relative risks. RESULTS: Fourteen studies (12 randomized and two non-randomized) comprising 730 athletes (mostly men with ages between 14 and 49 years) from different sports were included. Nine randomized studies were judged at high risk and three at low risk of bias, and the two non-randomized studies were judged at critical risk of bias. Seven randomized studies compared exercise-based interventions (e.g., L-protocol vs C-protocol), one randomized study compared the use of low-level laser therapy, and three randomized and two non-randomized studies compared injections of platelet-rich plasma to placebo or no injection. These low-level laser therapy and platelet-rich plasma studies complemented their interventions with an exercise program. Only three studies were judged at low overall risk of ineffectiveness (i-CONTENT). No single intervention or combination of interventions proved superior in achieving a faster TRTS/TRFT or reducing the risk of reinjury. Only eccentric lengthening exercises showed limited evidence in allowing a shorter TRFT. The platelet-rich plasma treatment did not consistently reduce the TRFT or have any effect on the risk of new hamstrings injuries. The certainty of evidence was very low for all outcomes and comparisons. CONCLUSIONS: Available evidence precludes the prioritization of a particular exercise-based intervention for athletes with acute hamstrings injuries, as different exercise-based interventions showed comparable effects on TRTS/TRFT and the risk of reinjuries. Available evidence also does not support the use of platelet-rich plasma or low-level laser therapy in clinical practice. The currently available literature is limited because of the risk of bias, risk of ineffectiveness of exercise protocols (as assessed with the i-CONTENT), and the lack of comparability across existing studies. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42021268499 and OSF ( https://osf.io/3k4u2/ ).

Magnetic resonance imaging is able to detect patellofemoral focal cartilage injuries: a systematic review with meta-analysis.

PURPOSE: The purpose of this study was to analyze the diagnostic accuracy of magnetic resonance imaging (MRI) to detect and grade the severity of patellofemoral (PF) cartilage injuries. METHODS: A systematic review was conducted on PubMed, EMBASE and Cochrane Library databases (up to July 1st 2022) to search for studies that reported the diagnostic accuracy of MRI to detect and grade PF cartilage injuries as compared to diagnostic arthroscopy. Risk of bias was judged using the QUADAS-2 tool. Quantitative syntheses were performed to calculate the diagnostic accuracy metric-sensitivity, specificity, positive likelihood (LR+) and negative likelihood (LR-) ratios, diagnostic odds ratio (DOR)-and presented as median with 25% and 75% percentiles. The summary receiver operating characteristic (SROC) curves were also calculated. Diagnostic accuracy metrics were calculated for all PF cartilage injuries and then sub-grouped by patellar and trochlear lesions. Diagnostic accuracy was also calculated according to the grading of cartilage injuries. RESULTS: Forty-five studies were included for qualitative analyses and forty studies were included for quantitative synthesis. A total of 3534 participants with a weighted mean age of 38.1 years were included. Diagnostic accuracy was generally high: sensitivity (0.8, 0.6-1.0), specificity (0.9, 0.8-1.0), LR+ (6.4, 3.1-15.3), LR- (0.3, 0.2-0.4) and DOR (21.3, 9.9-121.1). The area under the curve (AUC) of the SROC was 0.9. The diagnostic accuracy was slightly higher for patellar (sensitivity 0.8, specificity 0.8, LR+ 5.3, LR- 0.2, DOR 28.8) than for trochlear lesions (sensitivity 0.7, specificity 0.9, LR+ 5.5, LR- 0.4, DOR 14.3). The sensitivity was generally higher when grading advanced (vs. early or intermediate) cartilage injuries of the patella. CONCLUSION: The MRI is able to diagnose PF cartilage injuries with reasonably high diagnostic accuracy (as compared to arthroscopy). Clinicians can rely on MRI to reliably diagnose PF cartilage injuries (with some limitations) which will play an important role in deciding for surgical or non-operative treatment. LEVEL OF EVIDENCE: Level III.

Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy.

OBJECTIVE: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. BACKGROUND: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. METHODS: During 2017-2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. RESULTS: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. CONCLUSION: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

Mechanical-based therapies may reduce pain and disability in some patients with knee osteoarthritis: A systematic review with meta-analysis.

BACKGROUND: Mechanical-based therapies are not yet recommended to manage osteoarthritis (OA). This systematic review and meta-analysis aim to assess the effects of passive mechanical-based therapies (isolated or combined with other therapies) on patients with knee OA compared to placebo, other isolated or combined interventions. METHODS: Pubmed, Cochrane, Web of Science and EMBASE were searched up to December 2020. We included randomized and non-randomized trials using therapeutic ultrasound, phonophoresis, extracorporeal shockwave therapy (ESWT) and vibration (single or combined with other therapies) compared to placebo, and/or other physical therapies groups. Biochemical, patient-reported, physical and imaging outcome measures were retrieved. We judged risk of bias using the RoB2 tool for randomized studies, the ROBINS-I tool for non-randomized studies, and the GRADE to interpret certainty of results. RESULTS: We included 77 clinical studies. Ultrasound and ESWT statistically improved pain and disability comparing to placebo (combined or not with other therapies), and when added to other therapies versus other therapies alone. Ultrasound was statistically inferior to phonophoresis (combined or not with other therapies) in reducing pain and disability for specific therapeutic gels and/or combined therapies. Vibration plus exercise statistically improved pain relief and function versus exercise alone. All meta-analyses showed very-low certainty of evidence, with 15 of 42 (38%) pooled comparisons being statistically significant (weak to large effect). CONCLUSIONS: Despite the inconsistent evidence with very-low certainty, the potential benefits of passive mechanical-based therapies should not be disregard and cautiously recommended that clinicians might use them in some patients with knee OA.

Association between INDELs in MicroRNAs and Susceptibility to Gastric Cancer in Amazonian Population.

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.

Mepolizumab as a steroid-sparing treatment option in a patient with eosinophilic granulomatosis with polyangiitis / Mepolizumabe como terapêutica poupadora de esteroides num paciente com granulomatose eosinofílica com poliangiite

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem disorder characterized by asthma, peripheral blood eosinophilia, and signs of vasculitis. Glucocorticoids are considered the cornerstone of treatment, but most patients remain steroid-dependent and carry a significant burden of adverse effects. We report a case of a patient with steroid-dependent EGPA successfully treated with mepolizumab. A 36-year-old man presented with persistent rhinitis, dyspnea, wheezing, and dry cough poorly controlled with inhaled therapy. Eosinophilia in peripheral blood and bronchoalveolar lavage fluid was seen. Histological findings from nasal mucosa revealed eosinophilic microabscesses and vasculitis without granulomas compatible with EGPA diagnosis. After daily oral prednisolone (PSL) was started, symptoms and eosinophilia improved, but adverse effects emerged. Attempts at tapering off PSL resulted in worsening of symptoms. He started mepolizumab 300 mg monthly, with clinical improvement and sustained disease remission, which allowed reducing the need for PSL. We present a very disabling steroiddependent EGPA. Mepolizumab was able to taper off PSL while maintaining symptomatic control.

Granulomatose eosinofílica com poliangiite (EGPA) é uma doença multissistêmica caracterizada por asma, eosinofilia no sangue periférico e sinais de vasculite. Os corticoides são considerados a base do tratamento, no entanto, a maioria dos pacientes permanece dependente deste tratamento com os seus efeitos adversos associados. Relatamos o caso de um paciente com granulomatose eosinofílica dependente de esteroides com poliangiite (EGPA) tratado com sucesso com mepolizumabe. Um homem de 36 anos apresentou rinite persistente, dispneia, sibilos e tosse seca mal controlada com terapia inalada. Observou-se eosinofilia no sangue periférico e no lavado broncoalveolar. Os achados histológicos da mucosa nasal revelaram microabscessos eosinofílicos e vasculite sem granulomas compatíveis com o diagnóstico de EGPA. Após o início da prednisolona oral diária (PSL), os sintomas e a eosinofilia melhoraram, mas surgiram efeitos adversos. As tentativas de redução gradual da PSL resultaram no agravamento dos sintomas. Iniciou mepolizumabe 300 mg mensalmente, com melhora clínica e remissão sustentada da doença, o que permitiu reduzir a necessidade de PSL. Apresentamos um EGPA dependente de esteroides muito incapacitante. O mepolizumab foi capaz de diminuir o PSL mantendo o controle sintomático sustentado.

Effect of physical activity and exercise on telomere length: Systematic review with meta-analysis.

PURPOSE: To compare a physically active lifestyle or structured exercise program to physically inactive lifestyle or control groups on telomere length (TL). METHOD: We searched PubMed, EMBASE, Cochrane Library, and Open Gray databases up to March 31, 2020. We calculated standardized mean differences (SMD) with 95% confidence intervals (CI) of TL comparing physically active to physically inactive individuals and exercise intervention to control groups. Risk of bias was judged using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) for physical activity (PA) studies and the Cochrane risk-of-bias (RoB2) for exercise intervention studies. Certainty of evidence was judged using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included 30 studies (24 assessing the effects of PA and 6 assessing the effects of exercise interventions) comprising 7418 individuals. Physically active individuals had longer telomeres (SMD = 0.70, 95% CI 0.12-1.28, very-low certainty), especially in middle-aged individuals (SMD = 0.90, 95% CI 0.08-1.72, very-low certainty) and when considering only athletes (SMD = 0.54, 95% CI 0.18-0.90, very-low certainty). Trim-and-fill analyses revealed that most of the pooled effects were overestimated. Exercise interventions did not yield any significant effect on TL. CONCLUSION: There is very-low certainty that physically active individuals have longer telomeres with a moderate effect, but this effect is probably overestimated.

Investigation of INDEL variants in apoptosis: the relevance to gastric cancer.

BACKGROUND: Apoptosis is a type of cell death involved in different pathways inherent to the cell and the evasion from this mechanism has been related to cancer, although this process remains not very well comprehended. Gastric cancer (GC) is one of the most incident and aggressive types of cancer worldwide. In this study, we analyzed the distribution of INDEL variants in GC patients (Case) and individuals from the general population (Control) from the Amazon region, in which GC is remarkably frequent. METHODS: A panel of nine INDEL markers in apoptosis-related genes (BCL2 rs11269260, CASP3 rs4647655, CASP8 rs3834129 and rs59308963, CASP9 rs4645982 and rs61079693, FADD rs4197, FAS rs10562972 and TP53 rs17880560) was developed and genotyped by multiplex PCR in both groups. RESULTS: In our analyses, only marker rs4197 (FADD gene) was associated to GC development as follows: INS/DEL genotype of rs4197 increasing in about 2-fold the chances of developing this type of cancer (P = 0.046; OR = 1.940; 95%CI = 1.011-3.725). CONCLUSION: Our results suggest that rs4197 (FADD gene) might play a role in gastric carcinogenesis in the investigated population. More studies are needed to clarify this relation. Here, we highlight the importance of investigating INDEL variants in genes involved in apoptosis.

Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.

Mycobacterium chimaera Disseminated Infection.

The incidence and prevalence of nontuberculous mycobacterial disease is increasing due to enhanced clinician awareness and improved detection methods. The species identification using molecular microbiology techniques allows a better understanding of the differences in pathogenicity and treatment response. A 57-year-old man with a history of B-cell lymphoma in remission was transferred from the hematology department due to fever of unknown origin, night sweats and asthenia. The empirical antibiotic therapy was initiated with no clinical response, and he developed a subacute pneumonia, severe anemia and hepatosplenomegaly. After positive blood, bronchoalveolar lavage and bone marrow cultures, a disseminated Mycobacterium avium-intracellulare complex infection was diagnosed, and the patient began treatment with clarithromycin, rifabutin and ethambutol. Two weeks later, a fourth antibiotic was added, amikacin at first and then linezolid, with slow but gradual improvement. Due to amikacin-related severe kidney injury and linezolid-related severe myelosuppression, the fourth antibiotic was changed to moxifloxacin, which the patient tolerated. After 6 months of therapy, the sensitivity to the regimen was confirmed and the species was identified as Mycobacterium chimaera (MC), using the molecular genetic test GenoType NTM-DR. The blood and tissue cultures were negative after 4 months of therapy, and treatment was continued for 12 months. Although the infection was being treated successfully, the patient's B-cell lymphoma relapsed after 12 months and the patient died. This is a case report of a confirmed severe and disseminated MC infection in an immunocompromised patient using a molecular genetic test, successfully treated using a four-drug regimen.

Genes from the TAS1R and TAS2R Families of Taste Receptors: Looking for Signatures of Their Adaptive Role in Human Evolution.

Taste perception is crucial in monitoring food intake and, hence, is thought to play a significant role in human evolution. To gain insights into possible adaptive signatures in genes encoding bitter, sweet, and umami taste receptors, we surveyed the available sequence variation data from the 1000 Genomes Project Phase 3 for TAS1R (TAS1R1-3) and TAS2R (TAS2R16 and TAS2R38) families. Our study demonstrated that genes from these two families have experienced contrasting evolutionary histories: While TAS1R1 and TAS1R3 showed worldwide evidence of positive selection, probably correlated with improved umami and sweet perception, the patterns of variation displayed by TAS2R16 and TAS2R38 were more consistent with scenarios of balancing selection that possibly conferred a heterozygous advantage associated with better capacity to perceive a wide range of bitter compounds. In TAS2R16, such adaptive events appear to have occurred restrictively in mainland Africa, whereas the strongest evidence in TAS2R38 was detected in Europe. Despite plausible associations between taste perception and the TAS1R and TAS2R selective signatures, we cannot discount other biological mechanisms as driving the evolutionary trajectories of those TAS1R and TAS2R members, especially given recent findings of taste receptors behaving as the products of pleiotropic genes involved in many functions outside the gustatory system.