Clinical Outcomes and Graft Resorption After Metal-Free Bone Block Suture Tape Cerclage Fixation for Recurrent Anterior Shoulder Instability: A Computed Tomography Analysis.

BACKGROUND: Glenoid reconstruction with a bone block for anterior glenoid bone loss (GBL) has shown excellent outcomes. However, fixation techniques that require metal implants are associated with metal-related complications and bone graft resorption. HYPOTHESIS: Arthroscopic glenoid reconstruction using a tricortical iliac crest bone graft (ICBG) and metal-free suture tape cerclage fixation can safely and effectively restore the glenoid surface area in patients with recurrent anterior shoulder instability and anterior GBL. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Adult patients (≥18 years) of both sexes with recurrent anterior shoulder instability and anterior GBL ≥15% were enrolled. These patients underwent arthroscopic glenoid reconstruction with ICBGs and metal-free suture tape cerclage fixation. The effectiveness and clinical outcomes with this technique were evaluated at 24 months using functional scores. Resorption of the graft articular surface was assessed by computed tomography, with the graft surface divided into 6 square areas aligned in 2 columns. Descriptive analysis was conducted. RESULTS: A total of 23 consecutive patients met inclusion criteria (22 male, 1 female; mean age, 30.5 ± 7.9 years). The mean preoperative GBL was 19.7% ± 3.4%, and there were 15 allograft and 8 autograft ICBGs. All patients exhibited graft union at 3 months. The median follow-up was 38.5 months (interquartile range, 24-45 months). The Western Ontario Shoulder Instability Index, Rowe, Constant-Murley, and Subjective Shoulder Value scores improved from preoperatively (35.1%, 24.8, 83.1, and 30.9, respectively) to postoperatively (84.7%, 91.1, 96.0, and 90.9, respectively) (P < .001). No differences in clinical scores were observed between the graft types. One surgical wound infection was reported, and 2 patients (8.7% [95% CI, 2.4%-26.8%]) required a reoperation. The mean overall glenoid surface area increased from 80.3% ± 3.5% to 117.0% ± 8.3% immediately after surgery before subsequently reducing to 98.7% ± 6.2% and 95.0% ± 5.7% at 12 and 24 months, respectively (P < .001). The mean graft resorption rate was 18.1% ± 7.9% in the inner column and 80.3% ± 22.4% in the outer column. Additionally, 3 patients treated with an allograft (20.0% [95% CI, 7.1%-45.2%]), including the 2 with clinical failures, exhibited complete graft resorption at the last follow-up. CONCLUSION: Arthroscopic glenoid reconstruction using an ICBG and metal-free suture tape cerclage fixation was safe and effective, yielding excellent clinical outcomes. Resorption of the graft articular surface predominantly affected the nonloaded areas beyond the best-fit circle perimeter.

Long-term follow-up of total hip arthroplasty using polyethylene-ceramic composite (sandwich) liner.

INTRODUCTION: Ceramic-on-ceramic bearings have been widely used since their introduction in the 1970s. First-generation ceramics have very high fracture (breakage) rates. To overcome this, in the 1990s, modular cotyloid insert designs were developed, consisting of a ceramic and polyethylene composite (sandwich-type) liner; however, high implant fracture rates were observed in the medium term. We aimed to estimate the cumulative incidences of revision surgery (implant failure) and implant failure due to fractures, survival rates (time-to-revision surgery and time-to-fracture), and the long-term clinical and radiological outcomes in our series. METHODS: This was an observational, longitudinal, ambispective, single-centre study based on patients who underwent primary total hip arthroplasty (THA) using a sandwich-type liner (Cerasul), only available in our tertiary hospital between January 1999 and December 2002. Cumulative incidences were estimated and the 95% confidence interval (95% CI) was calculated. The Kaplan-Meier method was used to assess the time-to-revision surgery and time-to-fracture. RESULTS: 54 patients (49 men) were included, accounting for 59 sandwich-type linear implants. The mean (range) age was 47.4 (22-57) years. The primary THA indications were osteoarthritis (28 patients), osteonecrosis (14), childhood pathology sequelae (11), and inflammatory arthritis (6). The cumulative incidence of revision surgery by implants was 8.5% (5/59, 95% CI, 3.5-19.2%), 9.3% by patients (5/54, 95% CI, 4.0-19.9%), and 5.1% by implant fractures (3/59, 95%CI, 1.7-13.9%). The median (Interquartile Range, IQR) time-to-revision surgery was 158 (72.5-161) months, and the time to fracture was 182 (138-215) months. All primary THAs had good clinical and long-term survival outcomes. All implants had signs of solid fixation. CONCLUSIONS: After a 20-year follow-up period, the polyethylene-ceramic sandwich-type liner showed a long survival rate and low cumulative incidence of implant fracture; however, implant fractures remain the main complication. Orthopaedic surgeons should be aware that some patients still have this type of prosthesis and must be capable of responding quickly if a fracture occurs.

Radiculopathy with motor deficit: a cross-sectional study of the impact of the surgeon's experience on the indication and timing of surgical treatment.

PURPOSE: The optimal management of patients with compressive radiculopathy with motor deficit (CRMD) is controversial. Our goal was to provide evidence on the impact of the spine surgeons' experience on surgical planning and timing. METHODS: Spine surgeons were invited to participate in a 5-item online survey. A literature review was carried out. RESULTS: Of the 94 spine surgeons who responded to the survey, 70% would operate early on a patient with acute CRMD, but only 48% would do so if the radicular pain had resolved. Surgeons with more than 15 years of experience chose more conservative options. Twenty published studies were selected in the literature review. CONCLUSION: The optimal management of patients with compressive radiculopathy associated with a non-progressive motor loss remains unknown. The results of our survey show that surgeons with extensive surgical experience take a more conservative and cautious approach.

Eficacia de la dieta alta en fibra en la mejora del estreñimiento en pacientes con disinergia defecatoria en tratamiento con biofeedback anorrectal. Ensayo clínico exploratorio, aleatorizado / Effectiveness of a high fiber diet in improving constipation in patients with defecatory dyssynergy under treatment with anorrectal biofeedback. Exploratory, randomized clinical trial

Introducción: La fibra es el tratamiento inicial en el estreñimiento crónico funcional. Sin embargo, su papel en el grupo de pacientes con disinergia defecatoria no está bien establecido. El objetivo del estudio es evaluar la eficacia y la seguridad de la dieta alta en fibra en pacientes con disinergia defecatoria en el tratamiento con biofeedback anorrectal. Pacientes y métodos: Se realizó un ensayo clínico exploratorio, aleatorizado (1:1), doble ciego, controlado add-on, en un centro de referencia en España en pacientes con estreñimiento funcional y disinergia defecatoria de acuerdo con criterios de ROMAIV. Grupo control: tratamiento con biofeedback y dieta baja en fibra (15-20g/día). Grupo experimental: tratamiento con biofeedback y dieta alta en fibra (25-30g/día). Se analizó: respondedor (variable principal), paciente en quien la disinergia defecatoria se había corregido (>20% de reducción de la presión anal durante la maniobra defecatoria y prueba de expulsión del balón normal); parámetros anorrectales (relajación anal, reducción del esfuerzo); seguridad (síntomas abdominales: flatulencia, dolor, borborigmo, distensión). Resultados: Un total de 44 pacientes fueron aleatorizados: 22 por grupo. El porcentaje de respondedores fue del 75% (15/20; IC95%: 53-89%) grupo control y 70% (14/20; IC95%: 48-85%) grupo experimental, p=0,225. Solo se observaron diferencias a favor del grupo control en síntomas abdominales: flatulencias (p=0,028), distensión abdominal (p=0,041) y bienestar digestivo (p=0,043). Conclusión: En pacientes con disinergia defecatoria la dieta alta en fibra no solo no mejora la eficacia del biofeedback anorrectal, sino que se asocia a una pérdida de la mejoría de los síntomas abdominales. (AU)

Introduction: Fiber is the initial treatment in chronic functional constipation. However, its role in the group of patients with defecatory dyssynergy is not well established. The objective of the study is to evaluate the efficacy and safety of a high fiber diet in patients with defecatory dyssynergy in the treatment with anorectal biofeedback. Patients and methods: An exploratory, randomized (1:1), double-blind, controlled «add-on» clinical trial was carried out in a reference center in Spain in patients with functional constipation and defecatory dyssynergy according to the ROMEIV criteria. Control group: treatment with biofeedback and low-fiber diet (15-20g/day). Experimental group: treatment with biofeedback and high fiber diet (25-30g/day). Analyzed: responder (primary endpoint), patient whose defecatory dyssynergy had been corrected (>20% reduction in anal pressure during the defecation maneuver and normal balloon expulsion test); anorectal parameters (anal relaxation, reduced straining); safety (abdominal symptoms: flatulence, pain, borborygmus, bloating). Results: A total of 44 patients were randomized: 22 per group. The percentage of responders was 75% (15/20; 95%CI: 53 89%) control group and 70% (14/20; 95%CI: 48-85%) experimental group, P=.225. Differences in favor of the control group were only observed in abdominal symptoms: flatulence (P=.028), abdominal distension (P=.041) and digestive comfort (P=.043). Conclusions: In patients with defecatory dyssynergy, a high-fiber diet not only does not improve the efficacy of anorectal biofeedback but is associated with a loss of improvement in abdominal symptoms. (AU)

Percutaneous helical plate fixation in humeral shaft fractures with proximal extension.

BACKGROUND: Humeral shaft fractures with extension to the proximal third are increasingly frequent and technically more demanding. Surgical management of proximal metaphyseal junction humeral fractures is challenging. The aim of this study was to assess the safety, reproducibility, and possibility of early and completed rehabilitation in the percutaneous treatment with helical plates in humeral shaft fractures with proximal extension. PATIENTS AND METHODS: This was a descriptive, retrospective, single-centre cohort study based on consecutive patients with proximal metaphyseal junction humeral fractures (MIPO-helical-plate-Broggi's cohort). Surgical technique (minimally invasive approach and osteosynthesis): percutaneous treatment with a twisted plate (helical plates). STUDY VARIABLES: i): Intraoperative and postoperative (up to 1 year after surgery) safety; ii) Reproducibility of the surgical technique [number (percentage) of patients with surgical technique success]. The surgical technique success was defined as the recovering without neurovascular, implant failures and infection issues after one year follow up; and iii) Early and completed (3 months) rehabilitation [number (percentage) of patients]. A descriptive analysis was performed. RESULTS: Between April 2010 to January 2022, we received 443 humeral shaft fractures at our unit. Of these, 350 fractures were treated surgically. 157 (44.9%) were treated using the minimally invasive approach and osteosynthesis technique with extramedullary implants, of which 46 (46/157, 29.3%, 9 men and 37 women) were performed with almost orthogonally twisted Philos® helical plates. The median (range) age was 67 (51-94) years. STUDY OUTCOMES: i) Safety: None intraoperative events were gathered. No neurovascular, implant failure and infection issues were reported one year after surgery.; ii) Reproducibility of the surgical technique: only 1 failure (2%, 95%CI:0-11%), who was reoperated; and iii) Early and 3 month of rehabilitation was completed in 45 (98%, 95%CI:89-100%) patients. Forty-five (98%, 95%CI:89-100%) patients recovered their previous function the year after surgery. CONCLUSIONS: The treatment of humeral shaft fractures with proximal extension based on a minimally invasive approach and osteosynthesis: percutaneous treatment with a twisted plate (helical plates), as this is a submuscular and extraperiosteal technique, is a safe and reproducible technique, and promotes early rehabilitation. In our opinion, it is surgical technique whose main requirement is a good knowledge of topographic anatomy.

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

Measurement of apixaban concentrations in different human biological fluids by UHPLC-MS/MS. Clinical pharmacokinetic application in a subject with chronic kidney disease and nonvalvular atrial fibrillation on haemodialysis.

BACKGROUND: Apixaban's technical sheet does not recommend its use in clinical practice for patients with chronic kidney disease undergoing haemodialysis. However, recent studies indicate that apixaban could be a safe oral anticoagulant in these kinds of patients who do not present valvular atrial fibrillation. We developed and validated ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) procedures for measuring apixaban concentrations in plasma, dialysate liquid, and urine. MATERIAL AND METHODS: Simple protein precipitation was implemented to prepare samples. Chromatographic separations were achieved on an Acquity®-UPLC®-BEHTM (2.1x100 mm id, 1.7 µm) reverse-phase C18 column using a water/acetonitrile non-linear gradient containing 0.1 % formic acid at a 0.4 mL/min flow rate. Apixaban and its internal standard (apixaban-d3) were detected by electrospray ionisation mass spectrometry in positive and multiple reaction monitoring modes, using transitions of 460.3 â†’ 199.0/443.2 and 463.3 â†’ 202.0, respectively. RESULTS: No significant interferences and carry-overs were observed. Precisions, absolute relative biases, normalised-matrix factors, and normalised recoveries were ≤ 12.2%, ≤8.0%, 94.3-105.1%, and 93.9-105.4%, respectively. Linearity was observed between 5 and 500 µg/L for plasma/dialysate liquid and 5-1000 µg/L for urine. CONCLUSIONS: The validated UHPLC-MS/MS procedures could help support a pharmacokinetic study in non-valvular atrial fibrillation subjects with chronic kidney disease undergoing haemodialysis and apixaban-based anticoagulant therapy.

Effect and safety of listening to music or audiobooks as a coadjuvant treatment for chronic pain patients under opioid treatment: a study protocol for an open-label, parallel-group, randomised, controlled, proof-of-concept clinical trial in a tertiary hospital in the Barcelona South Metropolitan area.

BACKGROUND: Chronic non-cancer pain (CNCP) treatment's primary goal is to maintain physical and mental functioning while improving quality of life. Opioid use in CNCP patients has increased in recent years, and non-pharmacological interventions such as music listening have been proposed to counter it. Unlike other auditive stimuli, music can activate emotional-regulating and reward-regulating circuits, making it a potential tool to modulate attentional processes and regulate mood. This study's primary objective is to provide the first evidence on the distinct (separate) effects of music listening as a coadjuvant maintenance analgesic treatment in CNCP patients undergoing opioid analgesia. METHODS AND ANALYSIS: This will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints' evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation. ETHICS AND DISSEMINATION: The study protocol has been reviewed, and ethics approval has been obtained from the Bellvitge University Hospital Institutional Review Board, L'Hospitalet de Llobregat, Barcelona, Spain. The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05726266.

Feasibility of a multidisciplinary group videoconferencing approach for chronic low back pain: a randomized, open-label, controlled, pilot clinical trial (EN-FORMA).

BACKGROUND: Low back pain is a common condition that becomes even more prevalent with aging. A non-pharmacological multidisciplinary approach for chronic non-specific low back pain (CNSLBP) has been recommended, but integrating different healthcare professionals is challenging. A multidisciplinary group videoconferencing approach (MGVA) can be helpful. Our aim was to provide evidence on MGVA's feasibility in managing CNSLBP and its impact on clinical practice. METHODS: We conducted an open-label, randomized, controlled, parallel-group pilot clinical trial with CNSLBP patients irresponsive to conservative treatment. Patients between 18 and 67 years of age were randomly assigned (1:1) to either Standard-of-Care + MGVA (experimental group) or Standard-of-Care alone (control group). MGVA consisted of integrated sessions for physical rehabilitation/physiotherapy, psychology, and social work treatments. The control group received standard clinical practice treatment. The feasibility was assessed by the number of study procedures completed to at least 80% as planned. The impact on clinical practice was evaluated by the number of patients who changed their status from "candidate" to "non-candidate" to low back surgery as the treatment of choice for CNSLBP. The SF-36, Oswestry Disability Index, and TMMS-24 questionnaires were used. We performed a whole population-based descriptive analysis. RESULTS: We included 20 patients, but only 18 were randomized (2 withdrew consent before randomization). The mean (SD) age was 53.1 (5.9) years, and mostly women (13/18); 7 were actively employed. In the experimental group, 6/9 (67%, 95%CI:35-88%) patients attended at least 80% of the scheduled procedures, while in the control group, 8/9 (89%, 95%CI:57-98%) did. Additionally, 1 out of 4 (25%) patients in the experimental group changed their status from "candidate" for low back surgery to "non-candidate". None of the 2 patients in the control group did so. We found differences between groups in the SF-36 mental health component (p-value:0.061), Oswestry Disability Index (p-value:0.032), and TMMS-24 Repair component (p-value:0.014) at the end of the trial favoring MGVA. CONCLUSIONS: The multidisciplinary group videoconferencing approach to managing chronic non-specific low back pain was feasible, suggesting overall beneficial effects on patients' health and could play a role in changing a patient's status from "candidate" to "non-candidate" for surgery. TRIAL REGISTRATION: NCT05093543 (ClinicalTrials.gov), first registered in 26/10/2021.

Are iodophor-impregnated drapes associated with lower intraoperative contamination compared to no adhesive drape?: A protocol for systematic review and meta analysis.

BACKGROUND: Surgical site infection (SSI) is one of the most frightening complications after surgery. Adhesive drapes (AD) are widely used as an infection prevention tool. They can be non-impregnated or iodophor-impregnated, although non-impregnated are less used as they might be related to higher number of infections. One of the most common ways to study their efficacy is by analyzing the intraoperative contamination, which is a useful primary endpoint as it does not need follow-up and it has been strongly associated with infections. Therefore, we believe a systematic review (SR) and meta-analysis is needed to determine which is the literature available about this topic and to explore their results. METHODS: All randomized controlled trials (RCT) published since 1984 through to January 15, 2023 will be included. Non-human and experimental studies will be excluded. We will only include studies written in English. We will conduct searches in the following electronic databases: MEDLINE (via PubMed), SCOPUS and Web Of Science. The protocol of the SR was registered in PROSPERO under the number CRD42023391651 and was written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines. DISCUSSION: The evidence regarding the benefits of using iodophor-impregnated adhesive drapes (IIAD) is scarce. Therefore, this SR and meta-analysis is required to determine if they are related with a lower intraoperative contamination incidence, compared to no AD.

Home monitoring vs hospitalization for mild acute pancreatitis. A pilot randomized controlled clinical trials.

INTRODUCTION: Acute pancreatitis is a high-incidence benign disease. In 2009, it was the second highest cause of total hospital stays, the largest contributor to aggregate costs (approximately US$ 7000.00 per hospitalization), and the fifth leading cause of in-hospital deaths in the United States. Although almost 80% of acute pancreatitis cases are mild (usually requiring short-term hospitalization and without further complications), severe cases can be quite challenging.Classifications, scores, and radiological criteria have been developed to predict disease severity and outcome accurately; however, in-hospital care remains of widespread use, regardless of disease severity. A recent Turkish study reported that mild acute pancreatitis can be effectively and safely managed with home monitoring. Although the optimal timing for oral refeeding remains controversial and could cast some doubt on the feasibility of home monitoring, some guidelines already advocate for starting it within 24 hours.The present clinical trial aims to assess whether home monitoring is effective, safe and non-inferior to hospitalization for managing mild acute pancreatitis. METHODS: This will be a multicenter open-label randomized (1:1) controlled clinical trial to assess the efficacy and safety of home monitoring compared to in-hospital care for mild acute pancreatitis. All patients coming to the emergency department with suspected acute pancreatitis will be screened for enrollment. The main variable will be treatment failure (Yes/No) within the first 7 days after randomization. DISCUSSION: Acute pancreatitis implies a high economic burden in healthcare systems worldwide. Recent evidence suggests that mild disease can be safely and effectively treated with home monitoring. This approach may produce considerable cost savings and positively impact patients' quality of life. We expect the results to show that home monitoring is effective and not inferior to hospitalization for managing mild acute pancreatitis and that the economic costs are lower, kickstarting similar trials throughout the world, optimizing the use of limited healthcare budgets, and improving patients' quality of life.

Indocyanine green angiography-guided thyroidectomy versus conventional thyroidectomy for preserving parathyroid function: study protocol for a randomized single-blind controlled trial.

Introduction: Angiography with indocyanine green (ICG) fluorescence performed before thyroidectomy would allow identification of the vascularization of parathyroid glands, maximizing efforts for preserving functioning glands intraoperatively. The rationale of the study was based on the hypothesis that showing the vascular pattern of the parathyroid glands by means of ICG angiography before performing the thyroidectomy could prevent permanent hypoparathyroidism. Methods and analysis: We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy to identify the vascular pattern of the parathyroid glands versus conventional thyroidectomy in patients scheduled for elective total thyroidectomy. Patients will be randomized 1:1 to ICG angiography-guided thyroidectomy (experimental group) or conventional thyroidectomy (control group). Patients in the experimental group will undergo ICG angiography before thyroidectomy to identify the feeding vessels of the parathyroid glands and then, post-thyroidectomy ICG angiography to predict immediate parathyroid gland function by scoring the degree of fluorescence of the glands. Patients in the control group will undergo post-thyroidectomy ICG angiography only. The primary outcome measure will be the rate of patients with permanent hypoparathyroidism. Secondary outcome measures will be rate of postoperative hypoparathyroidism, the percentage of well vascularized parathyroid glands remaining in situ, the levels of iPTH and serum calcium after surgery and the influence of the type of vascular pattern of the parathyroid glands over these outcomes, as well as the safety profile of ICG angiography. Discussion: The results will contribute to adopt a new surgical strategy based on intraoperative ICG angiography before performing total thyroidectomy, according to which the rate of permanent hypoparathyroidism could be substantially reduced. Clinical trial registration: ClinicalTrials.gov. identifier NCT05573828.

Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.

The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-ß 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-ß 42/amyloid-ß 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Effectiveness of a high fiber diet in improving constipation in patients with defecatory dyssynergy under treatment with anorrectal biofeedback. Exploratory, randomized clinical trial. / Eficacia de la dieta alta en fibra en la mejora del estreñimiento en pacientes con disinergia defecatoria en tratamiento con biofeedback anorrectal. Ensayo clínico exploratorio, aleatorizado.

INTRODUCTION: Fiber is the initial treatment in chronic functional constipation. However, its role in the group of patients with defecatory dyssynergy is not well established. The objective of the study is to evaluate the efficacy and safety of a high fiber diet in patients with defecatory dyssynergy in the treatment with anorectal biofeedback. PATIENTS AND METHODS: An exploratory, randomized (1:1), double-blind, controlled «add-on¼ clinical trial was carried out in a reference center in Spain in patients with functional constipation and defecatory dyssynergy according to the ROMEIV criteria. CONTROL GROUP: treatment with biofeedback and low-fiber diet (15-20g/day). Experimental group: treatment with biofeedback and high fiber diet (25-30g/day). Analyzed: responder (primary endpoint), patient whose defecatory dyssynergy had been corrected (>20% reduction in anal pressure during the defecation maneuver and normal balloon expulsion test); anorectal parameters (anal relaxation, reduced straining); safety (abdominal symptoms: flatulence, pain, borborygmus, bloating). RESULTS: A total of 44 patients were randomized: 22 per group. The percentage of responders was 75% (15/20; 95%CI: 53 89%) control group and 70% (14/20; 95%CI: 48-85%) experimental group, P=.225. Differences in favor of the control group were only observed in abdominal symptoms: flatulence (P=.028), abdominal distension (P=.041) and digestive comfort (P=.043). CONCLUSIONS: In patients with defecatory dyssynergy, a high-fiber diet not only does not improve the efficacy of anorectal biofeedback but is associated with a loss of improvement in abdominal symptoms.

Three-Day Icatibant on Top of Standard Care in Patients With Coronavirus Disease 2019 Pneumonia: A Randomized, Open-Label, Phase 2, Proof-of-Concept Trial.

BACKGROUND: We aimed to evaluate icatibant, a competitive antagonist of the bradykinin B2 receptors, for the treatment of inpatients with coronavirus disease 2019 (COVID-19) pneumonia admitted in the early hypoxemic stage. METHODS: The randomized, open-label clinical trial of icatibant for COVID-19 pneumonia (ICAT·COVID, registered as NCT04978051 at ClinicalTrials.gov) was conducted in Barcelona. Inpatients requiring supplemental but not high-flow oxygen or mechanical ventilation were allocated (1:1) to treatment with either three 30-mg icatibant doses/d for 3 consecutive days plus standard care or standard care alone, and followed for up to 28 days after initial discharge. The primary and key secondary outcomes were clinical response on study day 10/discharge and clinical efficacy at 28 days from initial discharge, respectively. RESULTS: Clinical response occurred in 27 of 37 patients (73.0%) in the icatibant group and 20 of 36 patients (55.6%) in the control group (rate difference, 17.42; 95% confidence interval [CI], -4.22 to 39.06; P = .115). Clinical efficacy ensued in 37 patients (100.0%) in the icatibant group and 30 patients (83.3%) in the control group (rate difference, 16.67; 95% CI, 4.49-28.84; P = .011). No patient died in the icatibant group, compared with 6 patients (16.7%) in the control group (P = .011). All patients but 1 had adverse events, which were evenly distributed between study arms. No patient withdrew because of adverse events. CONCLUSIONS: Adding icatibant to standard care was safe and improved both COVID-19 pneumonia and mortality in this proof-of-concept study. A larger, phase 3 trial is warranted to establish the clinical value of this treatment. CLINICAL TRIALS REGISTRATION: NCT04978051.

Celecoxib-tramadol co-crystal in patients with moderate-to-severe pain following bunionectomy with osteotomy: A phase 3, randomized, double-blind, factorial, active- and placebo-controlled trial.

BACKGROUND: Celecoxib-tramadol co-crystal (CTC) is a first-in-class analgesic co-crystal of celecoxib and racemic tramadol with an improved pharmacologic profile, conferred by the co-crystal structure, compared with its active constituents administered alone/concomitantly. AIM: We evaluated CTC in moderate-to-severe acute postoperative pain. MATERIALS AND METHODS: This randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial (NCT03108482) was conducted at 6 US clinical research centers. Adults with moderate-to-severe acute pain following bunionectomy with osteotomy were randomized to oral CTC (200 mg [112 mg celecoxib/88 mg rac-tramadol hydrochloride] every 12 h), tramadol (50 mg every 6 h), celecoxib (100 mg every 12 h), or placebo for 48 h. Patients, investigators, and personnel were blinded to assignment. The primary endpoint was the 0-48 h sum of pain intensity differences (SPID0-48) in all randomized patients. Pain intensity was assessed on a 0-10 numerical rating scale (NRS). Safety was analyzed in patients who received study medication. Funded by ESTEVE Pharmaceuticals. RESULTS: In 2017 (March to November), 1323 patients were screened and 637 randomized to CTC (n = 184), tramadol (n = 183), celecoxib (n = 181), or placebo (n = 89). Mean baseline NRS was 6.7 in all active groups. CTC had a significantly greater effect on SPID0-48 (least-squares mean: -139.1 [95% confidence interval: -151.8, -126.5]) than tramadol (-109.1 [-121.7, -96.4]; p < 0.001), celecoxib (-103.7 [-116.4, -91.0]; p < 0.001), or placebo (-74.6 [-92.5, -56.6]; p < 0.001). Total treatment-emergent adverse events (TEAEs) were 358 for CTC and 394 for tramadol. Drug-related TEAEs occurred in 37.7% patients in the CTC group, compared with 48.6% in the tramadol group. There were no serious TEAEs/deaths. CONCLUSION: CTC provided greater analgesia than comparable daily doses of tramadol and celecoxib, with similar tolerability to tramadol. CTC is approved in the United States.

Usefulness of ICG Angiography-Guided Thyroidectomy for Preserving Parathyroid Function.

INTRODUCTION: Hypoparathyroidism is the most frequent complication after total thyroidectomy and, when permanent, it becomes a severe chronic disease. We assessed the usefulness of indocyanine green (ICG) angiography-guided thyroidectomy to reduce the postoperative hypocalcemia. METHODS: Prospective study with two consecutive cohorts of patients who underwent total thyroidectomy: historical control group (CG) and angiography-guided thyroidectomy group (AG). In all patients, ICG-angiography was performed at the end of the surgery to predict immediate parathyroid gland (PG) function. In the AG, ICG-angiography was also done after PG identification to show their vascular supply. We compared the rate of postoperative hypocalcemia (calcium supplementation needed due to hypocalcemia symptoms or calcium levels < 1.8 mmol/L on the first postoperative day) and permanent hypocalcemia (need of calcium ± vitamin D supplementation 12 months after thyroidectomy). RESULTS: We included 120 consecutive patients (84 CG; 36 AG). Thyroid cancer was the most common diagnostic (63.1% CG-69.4% AG; p = 0.646) and central neck dissection was also frequent (54.8% CG-64.3% AG; p = 0.468). The AG developed a lower rate of postoperative (26.2-5.6%; p = 0.011) and permanent hypocalcemia (11.9-0%; p = 0.032). The OR for permanent hypocalcemia was 0.673 (95% CI 0.591-0.766). A significant higher rate of well vascularized PG at the end of the surgery (score 2) in the AG (39.2-52.9%; p = 0.018) was also seen. CONCLUSION: ICG angiography-guided thyroidectomy is a useful tool to identify PG vascularization, allowing a better PG preservation and a significant decrease in hypocalcemia rates.

Lessons learned in aortoenteric fistula repair: a multidisciplinary team approach and diagnostic-therapeutic algorithm matter.

Aortoenteric fistula (AEF) is a low-prevalence, life-threatening condition regardless of treatment, with a 30-50% postoperative (≤60 days) mortality. This study aimed to estimate our postoperative cumulative mortality incidence and assess the feasibility of the diagnostic-therapeutic algorithm used in our clinical practice. We performed a retrospective cohort study of patients treated for AEF at a fully-equipped tertiary healthcare center between January 2008 and December 2020.