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The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson–Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad—cornea verticillate, neuropathic pain, and angiokeratomas—affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype–phenotype correlation could be useful from a practical clinical point of view and for future decision making. [ABSTRACT FROM AUTHOR]

We conducted a two-year retrospective evaluation of infants aged under two years with a confirmed, clinical, or suspected diagnosis of scabies in a healthcare center in Alicante (Spain) to determine possible factors associated with diagnostic delay and poor treatment response. We collected epidemiological, clinical, diagnostic, and treatment variables. After describing our findings as mean values and percentages, we compared categorical variables using the Student's t-test and the Mann–Whitney U test, and we compared continuous variables with the Chi2 test and Pearson's correlation coefficient. We included 51 infants (19 boys and 32 girls) with a mean age of 15 months. The main source of contagion was the family; half of the infants lived with four or more people. According to the International Consensus Criteria for the Diagnosis of Scabies, confirmed scabies was diagnosed in 45% of cases and clinical scabies in 47%, and 45% of cases had a diagnostic delay. Lesions mainly affected the hands, feet, and trunk, with papules in 92% of cases and burrows in 55%. The predominant symptoms were pruritus (94%) and irritability (69%). Regarding treatment, 98% of the infants received topical permethrin and 35% received oral ivermectin. Treatment failed in 76% of infants. Living in large family units was associated with a higher risk of contagion and therapeutic failure. Diagnostic delay was associated with previous misdiagnosis. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta‐analysis aims to evaluate the efficacy of pulmonary rehabilitation (PR) in improving dyspnea, fatigue, physical activity, quality of life, anxiety and depression in patients with Long COVID‐19 (LC). The impact of PR on LC and a comparison of face‐to‐face and telerehabilitation approaches was explored. Methods: This systematic review and meta‐analysis followed PRISMA guidelines and was registered in PROSPERO. A literature search included PubMed, Web of Science, and Cochrane Library until January 2023. No language filters were applied. Randomized controlled trials, non‐randomized controlled trials, and observational studies were included. The risk of bias was assessed using appropriate tools. Descriptive analysis and meta‐analysis were performed. Forest plots presented results. Statistical analyses were conducted using the Metafor Package in R v.3.4.2. Results/Findings: This systematic review and meta‐analysis included 16 studies on PR in LC patients. A total of 1027 adults were included. The studies varied in design, with seven observational studies, three quasi‐experimental studies, and six randomized controlled trials. Dyspnea, physical function, quality of life, psychological state, and fatigue were assessed as outcomes. The review found that pulmonary rehabilitation had a significant positive effect on dyspnea, physical function, quality of life (both global and physical domain), anxiety, and depression. However, the effect on fatigue was not significant. Heterogeneity was observed in some analyses, and publication bias was found in certain outcomes. Age and study design were identified as potential moderators. Both face‐to‐face and telerehabilitation interventions improved the studied outcomes, with only differences in the physical domain of quality of life favoring the face‐to‐face group. Implications on Physiotherapy Practice: PR improved dyspnea, physical function, quality of life, and psychological state in LC patients, but not fatigue. Face‐to‐face and telerehabilitation have similar effects, except for physical quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Cholangiocarcinoma (CCA) accounts for approximately 15% of primary liver cancers. CCA has a poor prognosis and, thus, more effective systemic treatments are needed. We tested opaganib and upamostat, drugs that target sphingosine kinase 2 and multiple serine proteases, primarily trypsins, which are highly expressed in CCA tumors. This study demonstrates the results of inhibiting these novel targets with these drugs individually and in combination in a patient-derived CCA xenograft mouse model. Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude mice. PAX165, a patient-derived xenograft (PDX) from a surgically resected CCA, expresses substantial levels of SPHK2, PRSS1, PRSS2, and PRSS3. Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group. [ABSTRACT FROM AUTHOR]

Objective: The present study evaluates the impact of family‐centered practices on families' ratings of social validity of telepractice in 659 Spanish families in early childhood intervention (ECI) services. Background: The integration of telepractice in ECI services has been accelerated by the social and health situation caused by the COVID‐19 pandemic. Until then, telepractice was a well‐known but scarcely used resource in early intervention. Social validity assessments are critical for telepractice because services are focused on supporting primary caregivers. Social validity, therefore, refers to whether the intervention approach and outcomes match the needs of children and families, allowing for improved planning, implementation, and evaluation of early intervention programs. Method: A survey‐based cross‐sectional study on families' ratings of social validity was carried out. A structural equations model was performed in order to assess the influence of families' ratings of the social validity of telepractice. The model analyzed a mediation through latent variables: family‐centered practices (X), fit of services to family needs (M), and social validity of telepractice (Y). Results: Our study shows an overall good perception of social validity of telepractice by families. Focusing on family needs and priorities and professionals encouraging families to have an active role completely mediates the relationship between family‐centered practices and family social validity scores. No differences in telepractice modalities were found. Conclusions and Implications: A family‐centered approach to telepractice in ECI is needed, not only for greater social validity, but also for improved child and family outcomes, especially when services support real family needs and priorities. [ABSTRACT FROM AUTHOR]

Simple Summary: Nodal control is a major challenge for locally advanced cervical cancer (LACC) treated with definitive chemoradiotherapy. The optimal radiotherapy regime for patients with node-positive disease is yet to be defined. Modern image-guided intensity-modulated radiotherapy offers the potential for dose escalation to involved nodes while minimizing doses to organs at risk. This study reports the efficacy and toxicity of a simultaneous integrated boost in an Asian cohort with node-positive LACC in the context of contemporary volumetric modulated arc therapy and magnetic resonance image-guided adaptive brachytherapy. A total of 234 involved nodes in 54 patients were analyzed. Excellent nodal control was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial regional nodal control (RNC), pelvic control (PC), locoregional control (LRC), disease free survival (DFS), and overall survival (OS) were 93%, 87%, 87%, 78%, and 85%, respectively. The incidence of grade ≥ 3 radiotherapy-related toxicity was low. The 5-year local experience demonstrated excellent treatment outcomes with an acceptable toxicity profile. This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55–57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1–16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity. [ABSTRACT FROM AUTHOR]

Background: Venous ulcers usually present a torpid evolution with a negative impact on patients' quality of life. In primary care, they account for 2.5% of nursing consultations and their treatment represents high costs for national health systems. These patients usually have a low level of physical activity, with muscle pump dysfunction of the lower limbs, which may improve with increased physical activity. The purpose of this study is to analyse the effectiveness of a structured intervention involving physical activity and exercise (Active Legs) as an adjuvant treatment in improving healing of chronic venous ulcers at 3 months follow-up. Methods: A randomized, multicentre clinical trial. A total of 224 individuals receiving primary nursing care with a diagnosis of venous ulcer, with a diameter of 1 cm or greater and an ankle-brachial index between 0.8 and 1.3, able to comply with the study requirements and consenting to participate, will be sequentially included (112 per group). Both groups will receive the standard treatment in primary care, with cleansing, debridement and healing in a moist environment together with multilayer compression therapy. The intervention group will also receive a structured educational intervention involving lower limb physical exercise and daily ambulation guidelines. The primary response variables will be complete healing –understood as complete and sustained epithelialisation for at least 2 weeks– and time to healing. The secondary variables will be degree of healing, ulcer area, quality of life, pain and variables related to the healing process, prognosis, and recurrences. Sociodemographic variables, adherence to treatment and satisfaction variables will also be recorded. Data will be collected at baseline, at 3 months and at 6 months follow-up. Survival analysis (Kaplan-Meier and Cox) will be performed to measure primary effectiveness. Intention-to-treat analysis. Discussion: If the intervention is effective, a cost-effectiveness analysis could be conducted and implemented as an additional intervention in the usual venous ulcer treatment in primary care. Trial registration: NCT04039789. [https://ClinicalTrials.gov]. 07/11/2019. [ABSTRACT FROM AUTHOR]

Background Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. Methods Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. Results Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40–62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3–55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P <.05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01–1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41–6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7–16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07–56.14), were associated with NTM infection. Conclusions Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors. [ABSTRACT FROM AUTHOR]

Alopecia areata (AA) represents an underrecognized burden in Latin America (LA), severely impacting quality of life (QoL). This impact is exacerbated by limited access to specialized dermatologic care and therapies for AA within and among nations. Many of the unmet needs for AA globally also exist in LA. The region has geographic, ethnic, cultural, and economic conditions. With new AA medicines targeting immunologic pathways on the horizon, LA must prepare regarding regulatory issues, reimbursement, awareness, and education to give adequate and timely treatment for patients with AA. To address these issues, the Americas Health Foundation convened a panel of six dermatologists from Argentina, Brazil, Colombia, and Mexico who are experts in AA and its comorbidities for a 3-day virtual meeting to discuss AA diagnosis and treatment in LA and create a manuscript offering recommendations to address discussed barriers. This publication examines unmet AA needs in LA, treatment, and innovative therapies and recommends improving AA care. Access constraints to conventional and novel medicines hinder appropriate treatments for patients. Therapy initiation delays can affect QoL, mental health, and disease progression. People with AA face stigmas, discrimination, and misconceptions owing to a lack of disease awareness. With promising new treatments for AA on the horizon, all stakeholders must coordinate efforts to enhance LA's AA management landscape and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. Methods We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. Results A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. Conclusions Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Bereaved siblings often receive insufficient social support and are at higher risk for mental disorders. This study aimed to examine the role of the therapist-rated working alliance in an online intervention for bereaved siblings. Clients (n = 74, 95% female), aged 17–59 received writing assignments and individual feedback by CBT trained therapists over 6 weeks. Working alliance (Working Alliance Inventory) and treatment outcomes (Inventory of Complicated Grief, Beck Depression Inventory-II) were assessed. Results revealed that the working alliance significantly increased during the course of the treatment and a significant association between working alliance and the change in depression was found. [ABSTRACT FROM AUTHOR]

To enhance therapeutic efficacy and reduce side effects in cancer treatment, multimodal therapies are increasingly desired. In particular, combined chemo‐ and photothermal therapy has been developed as an approach with significantly higher therapeutic efficacy. However, long‐term cytotoxicity arising particularly from poor biodegradability of the nanoparticles typically used for such treatment remains a challenge. In the present in vitro study, a new approach targeted toward cancer treatment that combines chemo‐ and photothermal therapy using bio‐derived polydopamine (PDA) bowl‐shaped mesoporous nanoparticles with exceptional biocompatibility is indicated. The potential of PDA mesoporous nanobowls as a new chemo‐ and photothermal agent was explored by loading the anti‐cancer drug doxorubicin (DOX) into nanobowls and investigating their photothermal performance upon near‐infrared (NIR) illumination. Strikingly, DOX loaded nanobowls show significantly higher pharmaceutical cytotoxicity to HeLa cells in vitro in comparison with free DOX due to their preferential uptake into cells. Following this with photothermal treatment resulted in nearly 100% cell death from the combined treatment of DOX loaded nanobowls and NIR illumination. This first step highlights the potential of PDA mesoporous nanobowls as a scaffold for combined chemo‐ and photothermal therapy for cancer treatment that offers new opportunities for combined physicochemical therapies to treat advanced disease states. [ABSTRACT FROM AUTHOR]

Background: Older adults with cancer use the emergency department (ED) for acute concerns. Objectives: Characterize the palliative care needs and clinical outcomes of advanced cancer patients in the ED. Design: A planned secondary data analysis of the Comprehensive Oncologic Emergencies Research Network (CONCERN) data. Settings/Subjects: Cancer patients who presented to the 18 CONCERN affiliated EDs in the United States. Measurements: Survey included demographics, cancer type, functional status, symptom burden, palliative and hospice care enrollment, and advance directive code status. Results: Of the total (674/1075, 62.3%) patients had advanced cancer and most were White (78.6%) and female (50.3%); median age was 64 (interquartile range 54–71) years. A small proportion of them were receiving palliative (6.5% [95% confidence interval; CI 3.0–7.6]; p = 0.005) and hospice (1.3% [95% CI 1.0–3.2]; p = 0.52) care and had a higher 30-day mortality rate (8.3%, [95% CI 6.2–10.4]). Conclusions: Patients with advanced cancer continue to present to the ED despite recommendations for early delivery of palliative care. [ABSTRACT FROM AUTHOR]

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Background: There is limited evidence for the use of zirconium dioxide implants in immediate implant placement as well as for related immediate loading protocols. The aim of this retrospective study was to investigate the survival rate, success and patient satisfaction of immediately placed zirconia implants compared to delayed placed implants. Methods: The study included 58 partially edentulous patients who were treated between 2013 and 2015 with immediate and delayed transgingival healing zirconium dioxide implants (SDS, Kreuzlingen/ Switzerland). In addition to survival and success rate, marginal bone loss was assessed using radiographs and soft tissue was evaluated using Pink Esthetic Score. Oral health-related quality of life was investigated prospectively using a modified OHIP questionnaire. Results: The cumulative survival rate of all implants included was 92% with 88% classified as full success. No significant difference was found between the bone levels of immediately and delayed placed and immediately and delayed loaded implants. The mean Pink Esthetic Score after final prosthetic rehabilitation was 12.2/14 points indicating excellent esthetic clinical results. Analysis of the OHIP questionnaire showed a mean value of 0.54/100 points reflecting a high patient satisfaction. Conclusions: Immediate and delayed placed as well as loaded zirconium dioxide implants showed excellent results regarding implant success and survival in this study. Zirconium dioxide implants may ensure excellent esthetic results and high patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Intra-articular infiltration of platelet-rich plasma (PRP) is an alternative therapeutic option to classic hyaluronic acid for the treatment of symptomatic knee osteoarthritis (KOA). However, variation in preparation methods and quality assessment of PRP makes the study of its real clinical efficacy difficult. Purpose: To (1) evaluate the clinical efficacy of a characterized PRP product prepared in a standardized manner and in a closed-system for the treatment of KOA and to (2) evaluate the association of the clinical response to PRP-related variables. Study Design: Case series; Level of evidence, 4. Methods: We recruited 130 patients with nonoperative KOA and evaluated them for 1 year. PRP was prepared from a donation of autologous blood, obtaining 3 aliquots of approximately 10mL of product, which were frozen, allowing platelet disruption, platelet factor release, and long-term storage, until administration. Patients were treated 3 consecutive times every 4 weeks with an intra-articular PRP knee injection under sterile conditions. Complete blood count was performed on the whole-blood sample and the processed PRP before freezing it, for product quality assessment. Patients were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and basic satisfaction scale at 3 months, 6 months, and 1 year after intervention. Results: Quality assessment confirmed a leukocyte-poor PRP product (white blood cell count, 0.09 ± 0.09 × 109/L) with a high platelet purity (platelet count, 630.86 ± 191.75 × 109/L). WOMAC scores improved, and basic satisfaction was achieved in 70% of patients. No adverse events were reported. No correlations were observed between PRP quality parameters and clinical results. PRP complete treatment production costs were €108/US$125 (€36/US$41.6 per injection). Conclusion: This standardized PRP production method resulted in improved WOMAC scores at 1 year postoperatively in 70% of patients with KOA. This technique was safe and affordable and ensured consecutive infiltrations with the same product to each patient. [ABSTRACT FROM AUTHOR]

Background: NT-proBNP is emerging as a novel tool for improving management of patients with heart failure (HF). The concept of health-related outcomes as the primary endpoint for therapeutic intervention in chronic disease, such as HF, should be the focal point going forward. Methods: We conducted a prospective real-world study in heart failure with reduced ejection fraction (HFrEF) patients. The main target was to evaluate the impact on patient's health-related outcomes of a personalized medical follow-up procedure, based on a laboratory model of risk stratification supported by NT-proBNP. One hundred and five consecutive patients admitted to the Hospital Heart-Failure unit were stratified into three groups (low, medium, and high risk) and prospective follow-ups during the 12 months post discharge. Results: It was found that patients under this new approach experienced early and robust improvements in patient health-related outcomes with consistency in most domains which persisted beyond 12 months post follow-up. Improvements in health related quality of life score (HRQLS) was observed over the time of the study. After 6 months we found a significant improvement in HRQLS of 18.2% (from 76.5 ± 22.4 to 95.0 ± 15.7) and 14.4% (from 76.5 ± 22.4 to 96.3 ± 15.9) after 12 months of follow-up (p < 0.001). The highest improvements were found in the symptom severity domain where patients reported an improvement of 22.6% after 6 months and 18.9% after 12 months (p < 0.001). The lowest scores were reported in the physical domain with increase of 11.0% and 4.3% after 6 months and 12 months (p = 0.089). Psychosocial domain and the ability to carry out the activities of normal life showed improvement as well. Conclusions: Our strategy based on NT-proBNP optimizes HFrEF management and represents a major new approach for clinical laboratories to improve patient health-related outcomes in HFrEF. [ABSTRACT FROM AUTHOR]

Hospitalized patients with coronavirus disease 2019 (COVID-19) experiencing respiratory symptoms have different complications (inflammatory, co-infection, and thrombotic) that are identifiable by analytics patterns. Personalized treatment decisions decreased early mortality (odds ratio [OR].144; 95% confidence interval [CI].03–.686; P  = .015). Increasing age (OR 1.06; P  = .038) and therapeutic effort limitation (OR 9.684; P  < .001) were associated with higher mortality. [ABSTRACT FROM AUTHOR]

Our study aimed to determine the effects of new-onset neurological symptoms (NNS) on clinically relevant outcomes in hospitalized patients with COVID-19 infection. We conducted a nationwide, comparative, retrospective, cohort study among adult, hospitalized COVID-19 patients involving 37 hospital sites from various regions in the Philippines. We included a total of 10,881 patients with confirmed COVID-19 infection (2008 had NNS while 8873 did not have NNS). The adjusted hazard ratios (aHRs) for mortality among the mild and severe cases were significantly higher by 1.660 (95% CI 1.132–2.435) and by 1.352 (95% CI 1.042–1.752), respectively, in the NNS group compared to those in the non-NNS group. The aHRs for respiratory failure in the NNS group were significantly increased by 1.914 (95% CI 1.346–2.722), by 1.614 (95% CI 1.260–2.068), and by 1.234 (95% CI 1.089–1.398) among the mild, severe, and critical cases, respectively. The aHRs for ICU admission in the NNS group were still significantly higher by 1.973 (95% CI 1.457–2.673) and by 1.831 (95% CI 1.506–2.226) among the mild and severe cases, respectively. Patients who had NNS were not significantly associated with a longer duration of ventilator dependence (adjusted odds ratio (aOR) 0.954, 95% CI 0.772–1.179), longer ICU stay (aOR 0.983, 95% CI 0.772–1.252) and longer hospital admission (aOR 1.045, 95% CI 0.947–1.153). The presence of NNS significantly increases the risk of mortality, respiratory failure and ICU admission among COVID-19 patients. Registration and associated protocol publication: ClinicalTrials.gov website (NCT04386083); Espiritu AI, Sy MCC, Anlacan VMM, Jamora RDG. The Philippine COVID-19 Outcomes: a Retrospective study Of Neurological manifestations and Associated symptoms (The Philippine CORONA study): a protocol study. BMJ Open. 2020;10:e040944. [ABSTRACT FROM AUTHOR]

Renal replacement treatment has not been generalized to the elderly for different reasons. The main objective of the present cohort study is to compare survival in patients older than 80 years with chronic kidney disease stage 5 on renal replacement treatment with those on conservative treatment. The use of healthcare resources is compared too. A Cox proportional hazards regression analysis was run with the outcome variable death during the follow‐up period. The independent variables were treatment type, age, gender, smoking habit, serum albumin, hemoglobin, Charlson Index, diabetes mellitus, arterial hypertension, ischemic cardiopathy, and neoplasm. For outcome variable "death," renal replacement treatment obtained a hazard ratio of 0.273 (P.006, CI95% 0.108‐0.686) vs conservative treatment. In conclusion, patients older than 80 years with chronic kidney disease stage 5 on renal replacement treatment presented a lower mortality risk than those receiving conservative treatment. Comorbidity and age are both associated with mortality, but do not cancel out the survival advantage. In healthcare resources, the renal replacement treatment group made greater use of tests, medical visits and consumption of hospital dispensing drugs, but there were no differences with respect to the days of hospital admission or assistance in home hospitalization. [ABSTRACT FROM AUTHOR]

Amelogenesis imperfecta (AI) is an inherited disease that expresses a disorder in the development of enamel structure. In its mildest form, it promotes tooth color change; and in more severe cases, it presents a loss of enamel structure initiated during the eruption phase. Different AI manifestations can coexist in the same patient or in the same tooth, both in the primary and permanent dentures. In addition, several subtypes are described, characterized according to the variety of phenotype and genotype. Successful treatment requires early diagnosis and therapeutic solutions involving different dental specialties. Although some professionals prefer to postpone permanent rehabilitation until the development of complete permanent dentures, the aesthetic and functional impact of this disease in childhood and adolescence requires that restorative treatment be started as soon as possible. The proposed therapies demonstrate numerous challenges such as extreme dentinal sensitivity, difficulties installing and maintaining the orthodontic appliance and the need for restorative and prosthetic intervention in malformed teeth. This work aims to demonstrate the interaction between Orthodontics, Restorative Dentistry and Prosthesis in the treatment of a patient with AI, reporting the success of treatment involving aesthetics, function and well-being and the long-term benefit of this interdisciplinary approach for patients with this disease. [ABSTRACT FROM AUTHOR]

Background: The semantic variant of primary progressive aphasia (svPPA) is characterized by a progressive loss of semantic knowledge impairing the ability to name and to recognize the meaning of words.Objective: We aimed to evaluate the immediate and short-term effect of errorless learning speech therapy on the naming and recognition of commonly used words in patients with svPPA.Methods: Eight participants diagnosed with svPPA received 16 sessions of intensive errorless learning speech therapy. Naming and word comprehension tasks were evaluated at baseline, immediately postintervention, and at follow-up after 1, 3, and 6 months. These evaluations were performed using two item sets (a trained list and an untrained list).Results: In the naming tasks, patients showed a significant improvement in trained items immediately after the intervention, but that improvement decayed progressively when therapy ended. No improvements were found either in trained comprehension or in untrained tasks.Conclusion: Errorless learning therapy could improve naming ability in patients with svPPA. This effect may be due to the relative preservation of episodic memory, but the benefit is not maintained over time, presumably because there is no consolidation. [ABSTRACT FROM AUTHOR]

Background: Amyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize l-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice. Methods: This work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing l-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ monoclonal antibody characterization by surface plasmon resonance, immunohistochemical staining of human and transgenic mouse brain, and the development and application of isoD7-Aβ ELISA as well as different non-modified Aβ ELISA. For antibody treatment studies, 12 mg/kg anti-isoD7-Aβ antibody K11_IgG2a was applied intraperitoneally to 5xFAD mice for 38 weeks. Treatment controls implemented were IgG2a isotype as negative and 3D6_IgG2a, the parent molecule of bapineuzumab, as positive control antibodies. Behavioral studies included elevated plus maze, pole test, and Morris water maze. Results: Our advanced antibody K11 showed a KD in the low nM range and > 400fold selectivity for isoD7-Aβ compared to other Aβ variants. By using this antibody, we demonstrated that formation of isoD7-Aβ may occur after formation of aggregates; hence, the presence of the isoD7-modification differentiates aged Aβ from newly formed peptides. Importantly, we also show that the Tottori mutation responsible for early-onset AD in a Japanese pedigree is characterized by massively accelerated formation of isoD7-Aβ in cell culture. The presence of isoD7-Aβ was verified by K11 in post mortem human cortex and 5xFAD mouse brain tissue. Passive immunization of 5xFAD mice resulted in a significant reduction of isoD7-Aβ and total Aβ in brain. Amelioration of cognitive impairment was demonstrated by Morris water maze, elevated plus maze, pole, and contextual fear conditioning tests. Interestingly, despite the lower abundance of the isoD7-Aβ epitope, the application of anti-isoD7-Aβ antibodies showed comparable treatment efficacy in terms of reduction of brain amyloid and spatial learning but did not result in an increase of plasma Aβ concentration as observed with 3D6 treatment. Conclusions: The present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy. [ABSTRACT FROM AUTHOR]

Despite the increasing incidence of metastatic melanoma in the older population, there is relatively limited specific data surrounding the use of immunotherapy for the treatment of advanced melanoma for patients above the age of 65 years. To date, there has not been a prospective trial done to evaluate the safety and efficacy of using immunotherapy to treat older patients with advanced melanoma. Older patients are often under-represented in clinical trials. In addition, older patients in clinical trials may have lower Eastern Cooperative Oncology Group (ECOG) performance score and fewer co-morbidities, and thus trial data may not truly reflect the experience of treating older patients. The purpose of this descriptive review is to examine the efficacy and safety data of the three currently approved immune checkpoint inhibitors for advanced melanoma treatment in older patients. Our review of available data established that the efficacy and tolerability of immunotherapy in older patients are comparable to results seen in younger patients. However, a dedicated, prospective, randomised trial to assess the safety, tolerability, and quality-of-life parameters of immunotherapy in the older population would provide further insight on the value of these treatments. [ABSTRACT FROM AUTHOR]

Introduction: The posterior malleolus (PM) is affected in around the 40% of ankle fractures. Anatomical reduction of the articular surface and fibular notch are essential for ankle stability and functional outcomes. These facts justify the increasing interest in the surgical treatment of PM in ankle fractures. Within this context, pre-operative computed tomography (CT) images and posterior approaches to the ankle play a crucial role. The aim of this paper is to make an accurate description of the literature and describe, according to authors' experience, the best surgical approach to the PM based on the CT findings while assessing their advantages and disadvantages.Methods: The fracture pattern of PM is classified according to Haraguchi or Bartoníček classification, both based on pre-operative CT scan images. The posterolateral (PLA) and posteromedial (PMA) approaches to the ankle and their corresponding modifications are described. We propose a decision-making algorithm for posterior malleolus fractures to facilitate treatment selection.Results: Posterolateral approach should be the election for Haraguchi I or III and Bartoníček 1, 2, or 4 fractures. Percutaneous PLA might be adequate in Haraguchi I and Bartoníček 1 to improve syndesmotic stability. In PL approaches, the fibula fracture may be addressed and fixed with a posterolateral plate or through a subcutaneous window that allows lateral reduction and fixation. Posteromedial approach should be the election for Haraguchi II and Bartoníček 3 fractures. A modified PMA might be the election to reduce and fix any fragment dependent on the anterior inferior tibiofibular ligament (AITFL). The modified PMA is performed in a supine position and allows us to check the articular reduction under direct vision. Both PMA are associated with a lateral fibular approach.Conclusion: To address the posterior malleolus when treating ankle fractures, surgeons should choose the most adequate approach based on the fracture pattern and their own experience. Anatomical reduction and stable fixation are critical to improve outcomes. [ABSTRACT FROM AUTHOR]

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Objective: To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies.Methods: We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes.Results: In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range = 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001).Interpretation: In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant, because one-third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody-associated disorder. ANN NEUROL 2020;87:256-266. [ABSTRACT FROM AUTHOR]

The article offers a study that focuses on the quantitative analysis of 18-FDG-PET/MRI to assess pathological complete response following neoadjuvant radiochemotherapy in locally advanced rectal cancer. It also mentions that Pathologic complete response (pCR) is observed in the cases of patients with locally advanced rectal cancer (LARC) treated with neoadjuvant radiochemotherapy (RCT).

Objective. The aim of this study was to investigate tear film optical quality dynamics for four types of silicone hydrogel contact lenses (SHCLs) for daily wear over a 15-day period and for different blink rate (BR) patterns. Methods. A prospective randomized, double-blind, cross-over pilot study including four SHCLs (A: lotrafilcon B (Air Optix plus HydraGlyde, Alcon Laboratories); B: samfilcon A (Ultra, Bausch & Lomb); C: comfilcon A (Biofinity, CooperVision); and D: filcom V3 (Blu:gen, Mark'Ennovy)). Serial measurements of Objective Scatter Index (OSI) using the HD Analyzer (Visiometrics S.L., Terrassa, Spain) were taken at different blinking patterns: blinking every 2.5 seconds (high BRs) and every 9 seconds (low BRs). They were performed during the first visit before CL insertion (baseline), after 20 minutes of CL wear (Day 1), and during the last visit after 8 hours of CL wear on day 15 of use (Day 15). Results. Normal young healthy subjects were recruited and fitted with the four lenses. For low BRs, the mean OSI value increased over time for all CLs and the slope of the curve also increased for all CLs, except for CL D. However, for high BRs, the mean OSI value increased only for CLs B and C and the slope of the curve did not change over time for any of them. Conclusions. These results suggest that the tear film optical quality dynamics after wearing SCHLs for 15 days seems to undergo a slight deterioration only for lowest BR. [ABSTRACT FROM AUTHOR]

The objective of this cross-sectional study was to evaluate the frequency, impact, and management of sexual dysfunction associated with commonly prescribed antidepressants available in psychiatry outpatient clinics in Spain. We recruited 2163 adult patients who had undergone treatment with antidepressants for at least 8 weeks and had a history of normal sexual functioning before the prescription of the antidepressant, except for mildly impaired libido. We used the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) for evaluating the frequency and tolerance of sexual dysfunction and whether this side effect was spontaneously reported. Overall, 79% patients showed sexual dysfunction, as indicated by a total score ≥ 3 on the PRSexDQ-SALSEX; 64% showed moderate-severe sexual dysfunction, with no differences between men and women on these outcomes. In the multivariate logistic regression analysis, treatment with a serotonergic antidepressant and having a severe clinical state of psychiatric illness were the factors associated with the highest likelihood of presenting with sexual dysfunction. Sexual dysfunction was spontaneously reported by 838 (41%) of the 2066 evaluable patients for this outcome. Among patients with sexual dysfunction, this condition was poorly tolerated by 22% of the patients, with these frequencies being significantly higher in men than in women. The most frequently used strategies employed by the psychiatrists in our study for dealing with sexual dysfunction were switching to another antidepressant (34%) and waiting for spontaneous resolution (33%). In conclusion, our results indicate that despite being a well-known, long-standing side effect of antidepressants, sexual dysfunction continues to be extremely common in patients receiving antidepressants, especially serotonergic ones, potentially jeopardizing treatment success in a substantial proportion of patients. There are important sex differences in the reporting and tolerance of sexual dysfunction that require further investigation. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the impact of right ventricular dysfunction (RVD) on outcome after transcatheter mitral valve repair (TMVR) in patients with chronic heart failure (CHF) and severe functional mitral regurgitation (FMR).Methods and Results: One hundred thirty patients (median age 72.7 ± 10.7 years; 63.8% male) at high operative risk (LogEuroSCORE 23.8 ± 13.9%) with FMR and CHF (left ventricular ejection fraction 32 ± 7%) were enrolled and separated into two groups according to the RVD. RVD was assessed by the tricuspid annular plane systolic excursion (TAPSE) method (A: TAPSE ≤ 16 mm, n = 58; B: TAPSE > 16 mm, n = 72). The rate of successful reduction of mitral regurgitation (MR ≤2+) by TMVR was similar in both groups (94.6% vs 91.2%; P: n.s.) with low in-hospital major adverse event rates. During a median follow-up period of 10.5 ± 4 months, the Kaplan-Meier analysis revealed a significantly higher all-cause mortality in group A (43.1% vs 23.6%; log-rank P = 0.039) and a significantly higher rate of hospital readmission due to congestive heart failure (56.9% vs 26.4%; log-rank P < 0.001). At long-term follow-up, 25% of patients in group A remained in NYHA functional class IV (none in group B). Preexisting RVD as assessed by TAPSE and Doppler tissue imaging (DTI-S') was an independent predictor of all-cause mortality after TMVR (hazard ratio 2.84; 95% confidence interval 1.15-7.65; P = 0.039; hazard ratio 4.70; 95% confidence interval 1.14-20.21; P = 0.044, respectively).Conclusions: Patients with CHF and RVD were with regard to functional capacity less often responder and showed an unfavorable long-term outcome. Thus, patients with CHF and RVD seem to benefit less frequently from TMVR. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of this study was to assess the impact of a phone assistance nursing program as an adjunct to conventional physiotherapy to increase adherence to a home exercise program on functional outcomes of patients who underwent shoulder instability surgery. METHODS: A randomized controlled study of 70 patients allocated to a phone assistance program (study group, n = 36 patients) or conventional postoperative management (control group, n = 34 patients) was conducted. All patients in both groups received conventional rehabilitation at the outpatient clinic after surgery. In addition, patients in the study group received phone calls from a nurse (who had access to a physiotherapist) 3 days per week. During the calls these patients received a coaching session about selfcare and support with the home exercise program. Evaluations were performed during a follow-up of 12 months for range of motion (ROM), pain (visual analog scale [VAS] score), Disability of the Arm, Shoulder, and Hand (DASH) score, Oxford Shoulder Instability Score (OSIS), and Rowe score. RESULTS: All scores significantly improved from preoperative to the final follow-up in both groups ( p = .001). At the final follow-up, there were no significant differences between groups in VAS, DASH, or Rowe scores. However, those in the study group had significantly better OSIS ( p = .013) and ROM ( p = .001), particularly for anterior forward motion ( p = .001). Likewise, the study group achieved full motion and function significantly faster than the control group ( p = .002). The amount of rehabilitation sessions at the outpatient clinic was 1.7 times higher in the control group ( p = .004) than in the study group. CONCLUSION: The phone assistance nursing program was an effective procedure to significantly improve the outcomes of conventional physiotherapy in patients who have undergone an operation for shoulder instability. [ABSTRACT FROM AUTHOR]

Background: Preclinical results showing therapeutic effect and low toxicity of metronomic chemotherapy with cyclophosphamide (Cy) + celecoxib (Cel) for mammary tumors encouraged its translation to the clinic for treating advanced breast cancer patients (ABCP).Patients and Methods: A single-arm, mono-institutional, non-randomized, phase II, two-step clinical trial (approved by Bioethics Committee and Argentine Regulatory Authority) was designed. Patients received Cy (50 mg po.d) + Cel (200 mg p.o.bid). Patient eligibility criteria included: ABCP who progressed to anthracyclines, taxanes and capecitabine, ≤4 chemotherapy schemes, with good performance status. Several pro- and anti-angiogenic molecules and cells were determined as biomarkers. Informed consent was signed by all patients. Primary endpoint was clinical benefit (CB).Results: Twenty patients were enrolled. Main clinical outcomes were prolonged disease stabilization and partial remission in 10/20 and 1/20 patients, respectively. CB was 55 %, and time to progression (TTP) was 21.1 weeks. Median TTP in patients who achieved CB was 35.6 weeks, and mean overall survival was 44.20 weeks. There were no grade 3/4 toxicities associated with treatment. Circulating endothelial cells (CECs) increased at the time of progression in patients who showed CB (P = 0.014). Baseline CECs and circulating endothelial progenitor cells showed marginal associations with TTP. Serum VEGF decreased (P = 0.050), sVEGFR-2 increased (P = 0.005) and VEGF/sVEGFR-2 ratio decreased during treatment (P = 0.041); baseline VEGF and VEGF/sVEGFR-2 were associated with TTP (P = 0.035 and P = 0.030, respectively), while sVEGFR-2 did not.Conclusions: Treatment was effective, showing low toxicity profile and excellent tolerability. The combination had anti-angiogenic effect. Increased levels of CEC could be useful for detecting progression. Baseline VEGF and VEGF/sVEGFR-2 values could be useful as early predictors of response.Trial Registration: ANMAT#4596/09. [ABSTRACT FROM AUTHOR]

Background: Subtalar arthrodesis is a treatment option for pain due to posttraumatic arthritis following calcaneal fractures. The goal of this study is to examine the results of arthroscopic subtalar arthrodesis for posttraumatic arthritis following calcaneal fractures.Patients and Methods: We performed a retrospective case series reviewing 37 consecutive patients (36 male) treated for posttraumatic arthritis following calcaneal fractures by arthroscopic subtalar arthrodesis. The fractures were due to high-energy injuries in 81% of cases, and 12 fractures (32.4%) had been previously treated with internal fixation. Average follow-up was 57.5 months.Results: Average American Orthopedic Foot and Ankle Society (AOFAS) scores significantly improved from 49.0 ± 10.9 points preoperatively to 76.0 ± 8.0 points at final follow-up. Average time to union was 12.5 weeks. Six patients (16.2%) suffered complications: superficial wound infection (2.7%), symptomatic hardware that warranted removal (5.4%) and nonunion (8.1%) presented nonunion. All three cases had prior internal fixation through an extensile lateral approach, and fused after a repeat surgery.Conclusion: Arthroscopic subtalar arthrodesis offers consistent improvement in cases of posttraumatic arthritis following calcaneal fractures, with a union rate similar to published series of open arthrodesis. We observed more nonunions in patients who had been treated previously with internal fixation. In spite of this, we continue to recommend arthroscopic subtalar arthrodesis, as it preserves the soft tissue envelope better than open techniques. [ABSTRACT FROM AUTHOR]

Background: Nucleic acid-targeted pathogen inactivation technology using amustaline (S-303) and glutathione (GSH) was developed to reduce the risk of transfusion-transmitted infectious disease and transfusion-associated graft-versus-host disease with red blood cell (RBC) transfusion.Study Design and Methods: A randomized, double-blind, controlled study was performed to assess the in vitro characteristics of amustaline-treated RBCs (test) compared with conventional (control) RBCs and to evaluate safety and efficacy of transfusion during and after cardiac surgery. The primary device efficacy endpoint was the postproduction hemoglobin (Hb) content of RBCs. Exploratory clinical outcomes included renal and hepatic failure, the 6-minute walk test (a surrogate for cardiopulmonary function), adverse events (AEs), and the immune response to amustaline-treated RBCs.Results: A total of 774 RBC unis were produced. Mean treatment difference in Hb content was -2.27 g/unit (95% confidence interval, -2.61 to -1.92 g/unit), within the prespecified equivalence margins (±5 g/unit) to declare noninferiority. Amustaline-treated RBCs met European guidelines for Hb content, hematocrit, and hemolysis. Fifty-one (25 test and 26 control) patients received study RBCs. There were no significant differences in RBC usage or other clinical outcomes. Observed AEs were within the spectrum expected for patients of similar age undergoing cardiovascular surgery requiring RBCs transfusion. No patients exhibited an immune response specific to amustaline-treated RBCs.Conclusion: Amustaline-treated RBCs demonstrated equivalence to control RBCs for Hb content, have appropriate characteristics for transfusion, and were well tolerated when transfused in support of acute anemia. Renal impairment was characterized as a potential efficacy endpoint for pivotal studies of RBC transfusion in cardiac surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the efficacy and safety of valsartan (V) or chlorthalidone (C) monotherapy in comparison with a fixed combination of valsartan and chlorthalidone (V + C). METHODS: This 12-week multicenter randomized three-arm open-label study randomly allocated 72 patients to V or C as monotherapy or a combination of V + C. The aim was to measure changes in office systolic blood pressure (SBP) and diastolic blood pressure (DBP) and in 24-hour ambulatory blood pressure monitoring (ABPM) from baseline to week 12, in addition to medication tolerability. RESULTS: The proportion of patients achieving target BP in office at week 12 was not statistically different for the three groups. However, comparisons of daytime and nighttime 24-hour ABPM values from baseline to week 12 revealed significant differences in nighttime mean SBP for the three groups, due to a significantly greater reduction in the values in patients assigned to the V + C group (-14.7 vs. -8.7 vs. -10.7, P = .042, V+C; V; C, respectively). Although patients assigned to the V + C group also had greater nighttime reduction in mean DBP values compared with those in the other groups, this difference was not statistically significant. The incidence of adverse events did not differ significantly. CONCLUSION: In patients with hypertension treated with V, C, and both medications combined, the fixed combination of V + C provided a significantly greater reduction of late night to early morning BP values when interventions were assessed with 24-hour ABPM. [ABSTRACT FROM AUTHOR]

Background: The majority of clinical practice guidelines do not recommend the use of SYSADOA (Symptomatic Slow Action Drugs for Osteoarthritis) for the treatment of osteoarthritis because of the lack of evidence or uncertainty around their efficacy. Nevertheless, the Spanish Public Health Service continues funding these drugs. Aim: The aim of this study is to describe the prescription status of SYSADOA in the primary care units of the Basque Country during 2011; to determine if variability exists among them; and to examine if the variability could be explained by the health care region each PC unit belongs to. Methods: Prescription data for SYSADOA during 2011 was obtained from the Basque Ministry for Health. In the Basque Country, primary care is divided into seven regions, each region consisting of several primary care units, which were used as the unit of analysis. Defined daily doses (DDD) per 1,000 inhabitant-days (DHD) were calculated. Data were standardized by sex and age using the total population of the Basque Country as the reference population. Small area statistics were calculated (extremal quotient, coefficient of variation and systematic component of variation). The influence of the region to which primary care units belonged was also analysed. R software (version R-2.15.0) was used for the analysis. Results: SYSADOA prescription during 2011 accounted for an expense of 4.5 million euros for the Basque Health Service. The crude rate of consumption of SYSADOA was 7.81 DDD per 1,000 inhabitant-days. The obtained external quotient was 13.67. The prescription of SYSADOA of the primary care units located in the 95th percentile was six times higher than the ones located in the 5th percentile. The region to which units belonged accounted for 57% of the observed variability. Discussion: The uncertainty around these drugs could be reflected in the existing variability of their prescription level. The analysis of the variability in the prescription of drugs with no demonstrated efficacy could help in allocating resources into other services or health technologies supported by evidence, thereby contributing to the improvement of health outcomes. [ABSTRACT FROM AUTHOR]

Objectives. To describe the past 20 years’ correction modalities for keratoconus and their visual outcomes and possible complications. Methods. A review of the published literature related to the visual outcomes and possible complications in the context of keratoconus management using nonsurgical procedures for the last 20 years (glasses and contact lenses) was performed. Original articles that reported the outcome of any correction modalities of keratoconus management were reviewed. Results. The most nonsurgical procedure used on keratoconus management is the contact lens fitting. Soft contact lenses and soft toric contact lenses, rigid gas-permeable contact lenses, piggyback contact lens system, hybrid contact lenses, and scleral and corneoscleral contact lenses form the contemporary range of available lens types for keratoconus management with contact lenses. All of them try to restore the vision, improve the quality of life, and delay surgical procedures in patients with this disease. Complications are derived from the intolerance of using contact lens, and the use of each depends on keratoconus severity. Conclusions. In the context of nonsurgical procedures, the use of contact lenses for the management of keratoconic patients represents a good alternative to restore vision and improve the quality of live in this population. [ABSTRACT FROM AUTHOR]

Background: Multiple factors can account for surgical complexity during laparoscopic partial nephrectomy (LPN); severe adhesion of perirenal fat (PRF) is a crucial one. Consequent renal decapsulation can deem renorrhaphy a very challenging task. We propose a novel technique (synthetic renal capsule tailoring [SYRCT]) to facilitate renorrhaphy in decapsulated kidneys and suggest early decapsulation as a safe option in cases with severe PRF.Materials and Methods: We retrospectively analyzed perioperative results of this novel technique performed in cases with severe PRF. All cases were classified as high grade in the Mayo Adhesive Probability (MAP) score.Results: A total of six cases were performed with the SYRCT technique. All patients were male with a mean age of 70 years (62-76 years) and mean body mass index of 30 kg/m2 (23.66-33.86). Of the six cases, five were T1a and 1 T1b. Mean tumor size was 2.83 cm (range 1.2-6 cm). Mean operative time was 121 minutes (range 74-150 minutes); mean warm ischemia time was 17.2 minutes (range 13-25 minutes). Mean operative bleeding was 128 mL (range 50-250 mL). Mean hospital stay was 2.3 days. There were no surgical complications greater or equal to Clavien II.Conclusion: Performing complete renal decapsulation with subcapsular dissection and SYRCT in cases with high MAP score and severe PRF is safe and reproducible. Using this novel technique, we were able to obtain perioperative results comparable to the ones we found in LPN with normal PRF. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation of the continuous renal replacement therapy (CRRT) circuit is an important technical aspect of this medical procedure. Most studies evaluating the efficacy and safety of citrate use have been carried out in adults, and little evidence is available for the pediatric patient population. The aim of this study was to compare regional citrate anticoagulation versus systemic heparin anticoagulation in terms of the lifetime of hemofilters in a pediatric population receiving CRRT at a pediatric center in Bogota, Colombia. Methods: This was an analytical, observational, retrospective cohort study in which we assessed the survival of 150 hemofilters (citrate group 80 hemofilters, heparin group 70 hemofilters) used in a total of 3442 hours of CCRT (citrate group 2248 h, heparin group 1194 h). Hemofilter survival was estimated beginning at placement and continuing until filter replacement due to clotting or high trans-membrane pressures. Results: Hemofilter survival was higher in the citrate group than in the heparin group (72 vs. 18 h; p <0.0001). Bivariate analysis showed that the hemofilter coagulation risk was significantly increased when heparin was used, regardless of hemofilter size and pump flow (hazard ratio 3.70, standard error 0.82, 95% confidence interval 2.39-5.72; p <0.00001). Conclusions: Regional citrate anticoagulation could be more effective than heparin systemic anticoagulation in terms of prolonging the hemofilter lifetime in patients with acute renal injury who require CRRT. [ABSTRACT FROM AUTHOR]

Purpose: The goal of this study was to describe the surgical technique and our results with arthroscopic posterior subtalar arthrodesis.Material and Methods: Retrospective case series of 65 patients (38 men and 27 women) averaging 50 years of age (range 21-72 years) undergoing posterior arthroscopic subtalar arthrodesis using one or two percutaneous 6.5-7.3mm screws between May 2004 and February 2011, with a mean follow-up of 57.5 months (range 24-105 months).Results: We achieved a 95.4% union rate after an average of 12.1 weeks (range 9 to 16 weeks). 12.3% of patients suffered complications, including superficial infection, nonunion and need for hardware removal. The AOFAS score improved from 51.5 points (19-61 points) preoperatively to 81.9 points (60-94 points) in the postoperative period.Conclusions: We describe the surgical technique for arthroscopic subtalar arthrodesis, which as proven to be a safe and reliable technique in our experience, with consistent improvements in AOFAS scores. [ABSTRACT FROM AUTHOR]

Introduction: Surgical resection of liver metastases from colorectal and neuroendocrine tumours has become a standard of care for resectable patients with isolated hepatic disease and good performance status, leading to extended survival in a carefully selected subgroup of these patients. However, the role of hepatic surgery in gastric and oesophageal liver metastases is controversial and not clearly defined. Areas covered:a systematic electronic literature search was performed to select the most representative evidence regarding hepatectomies in liver metastases from these two tumours. PubMed, Medline, Embase Ovid and Google Scholar databases were scanned for articles written in English and published in peer-reviewed journals between 1994 and May 2016. Expert commentary: Given the shortage of randomised studies and the limited number of patients in many of the studies discussed here, the evidence base for the use of hepatectomies in these settings is not strong. Thus, while the data for resections of gastric liver metastases may in particular seem encouraging, the results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: C-met and its ligand, hepatocyte growth factor (HGF) have been associated with the resistance mechanism of EGFR-TKIs. HGF was evaluated as a clinical-marker of response in NSCLC patients treated with afatinib.Methods: Sixty-six patients with stage IIIB/IV lung adenocarcinoma and progression to any-line chemotherapy received afatinib 40 mg/day. Mutational EGFR and HER2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Serum HGF content was measured by ELISA before and 2 months after the start of treatment. HGF levels were assessed with the objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS). This trial was registered on ClinicalTrials.gov: NCT01542437.Results: Fifty patients (75 %) were EGFR mutation positive. Response was achieved in 59 % of all patients and 78 % of EGFR mutated patients. Median PFS was 10 [95 % CI 6.8-13.1] and 14.5 months [10.9-18.9] for all and EGFR mutated patients, respectively. Median OS was 22.8 [17.5-28.1] and 32.4 months [18.3-46.6] for all and EGFR mutated patients, respectively. Patients with reduced serum HGF levels had improved ORR (75 % vs 44 %; p = 0.011), PFS (15.1 [2.9-27.3] vs 6.5 months [3.9-9.1]; p = 0.005) and OS (NR vs 14.5 months [7.8 - 21.3] p = 0.007). A reduction in serum HGF levels was an independent factor associated with longer PFS (HR 0.40; p = 0.021) and OS (HR 0.31; p = 0.006) in all and EGFR mutated patients.Conclusions: A reduction in serum HGF levels was associated with improved outcomes in patients treated with afatinib. These results suggest HGF might have a role as a mechanism of resistance to EGFR-TKIs. HGF could represent a potential therapeutic target to prevent or reverse resistance particularly in EGFR mutated patients. [ABSTRACT FROM AUTHOR]

The article offers information on the study of analyzing the oncological treatment of nonagenarian metastatic colorectal cancer (mCRC) patients. It mentions the aim of the study was to investigate the cancer characteristics, treatments administered and outcomes for nonagenarians and centenarians diagnosed with mCRC using our state-wide population-based mCRC registry to understand the current patterns of care and outcomes in this age subgroup of patients.

Background: Residual depressive symptoms are associated with a poor prognosis for relapse or recurrence and are recognized as impeding factors of functionality. Recovery to the pre-depression level of functioning should be the goal of treatment.Aim: To evaluate outcomes in depressed outpatients treated with escitalopram regarding response, recovery, residual symptoms, functionality and ability to work over 48 weeks.Method: 3278 outpatients were evaluated at weeks 8, 24 and 48. A simple questionnaire was used to rate severity of illness, impairment of functionality, treatment response, tolerability, presence and severity of residual symptoms, whether remission with residual symptoms or recovery was achieved, and to what degree the patient was able to work.Results: Data over the full 48-week period were available for 75.8% of patients, for whom treatment response was rated as "very good" or "good" in 81%. However, only 42% of the completing patients achieved recovery without residual symptoms, while 41% were rated as remitters with residual symptoms. Lack of energy/motivation was the most common reported residual symptom and was present in 23.5% of patients at study end. Concentration difficulties were present in 15.8% and impaired sleep in 13.9% of patients. Complete inability to work decreased from 36% at baseline to 9% at week 48, while full-time working capacity increased from 37% to 62%.Limitations: Non-controlled observational real life study using simple ratings rather than established rating scales.Conclusion: <50% of patients completing a one-year antidepressant treatment regimen were rated as being symptomatically fully recovered, and ≈50% still reported functional deficits. [ABSTRACT FROM AUTHOR]

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 μg/mL and 0.5 μg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications. [ABSTRACT FROM AUTHOR]

Background: Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window. Aims: We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset. Methods: Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2- patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0-2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2. Results: We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1-9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1-75.8). Conclusions: This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window. [ABSTRACT FROM AUTHOR]

Science and Technology Parks (STP) have attracted considerable attention and public funds in recent years. However, the conclusions on their effectiveness remain mixed. This work evaluates the impact of STP on firm product innovation in the Spanish context, as an example of a less developed innovation system in which regional and national governments are prioritizing STP initiatives. This work draws on a large sample of firms provided by the Spanish Survey on Technological Innovation that is conducted annually by the National Statistical Institute. We explore alternative econometric methods to obtain average treatment effects for firms located in 22 Spanish STPs. Our results show that Spanish STPs have a strong and positive impact on the probability and amount of product innovation achieved by STP located firms. These results hold when the endogeneity of STP location is taken into account. [ABSTRACT FROM AUTHOR]

Metronomic chemotherapy refers to the chronic, equally spaced, delivery of low doses of chemotherapeutic drugs, without extended interruptions. Previously, we developed two combined metronomic schemes for the treatment of murine mammary tumors. The aim of this study was to compare their effects on tumor and metastasis growth, survival, and toxicity. Metronomic chemotherapy with Cyclophosphamide + Celecoxib (Cy + Cel) showed higher antimetastatic power than Cyclophosphamide + Doxorubicin (Cy + Dox), while being similar in other aspects. That difference, plus the advantage that represents its oral administration, suggests that the Cy + Cel combination is more suitable than Cy + Dox for metronomic chemotherapy of mammary tumors and could be proposed to the translation to the clinic. [ABSTRACT FROM AUTHOR]

Background: Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning. Methods: At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome. Results: Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome. Conclusions: Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches. [ABSTRACT FROM AUTHOR]