Exercise and Pain Neuroscience Education for Patients With Chronic Pain After Total Knee Arthroplasty: A Randomized Clinical Trial.

Importance: Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population. Objective: To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA. Design, Setting, and Participants: A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark. Participants with moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least 1 year after primary TKA were included. Participant recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023. Interventions: The study included 24 sessions of supervised neuromuscular exercise (2 sessions per week for 12 weeks) and 2 total sessions of pain neuroscience education (6 weeks between each session) or the same pain neuroscience education sessions alone. The interventions were delivered in groups of 2 to 4 participants. Main Outcomes and Measures: The primary outcome was change from baseline to 12 months using the mean score of the Knee Injury and Osteoarthritis Outcome Score, covering the 4 subscales pain, symptoms, activity of daily living, and knee-related quality of life (KOOS4; scores range from 0 to 100, with higher scores indicating better outcomes). The outcome assessors and statistician were blinded. All randomized participants were included in the intention-to-treat analysis. Results: Among the 69 participants (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) included in the study, 36 were randomly assigned to the neuromuscular exercise and pain neuroscience education group, and 33 to the pain neuroscience education-alone group. The intention-to-treat analysis showed no between-group difference in change from baseline to 12 months for the KOOS4 (7.46 [95% CI, 3.04-11.89] vs 8.65 [95% CI, 4.67-12.63] points; mean difference, -1.33 [95% CI, -7.59 to 4.92]; P = .68). Among the 46 participants who participated in the 12-month assessment in the 2 groups, 16 (34.8%) experienced a clinically important improvement (a difference of ≥10 points on the KOOS4) with no between-group difference. No serious adverse events were observed. Conclusions and Relevance: In this randomized clinical trial, the results demonstrated that neuromuscular exercises and pain neuroscience education were not superior to pain neuroscience education alone in participants with chronic pain after TKA. Approximately one-third of the participants, regardless of intervention, experienced clinically important improvements. Future studies should investigate which patient characteristics indicate a favorable response to exercises and/or pain neuroscience education. Trial Registration: ClinicalTrials.gov Identifier: NCT03886259.

Tension band versus locking plate fixation for patella fractures - a protocol of a randomised controlled trial.

INTRODUCTION: Following surgical management of patella fractures, patients commonly report pain; difficulties with weight-bearing tasks such as walking, running and climbing stairs; and restrictions in quality of life. Recently, a locking plate system for surgical management of patella fractures has been introduced. To date, no studies have compared standard treatment with tension band wiring with locking plate fixation in a randomised study design. We aim to compare the one-year patient-reported Knee Injury and Osteoarthritis Outcome subscale scores (KOOS5-subscales) after standard care tension band fixation with locking plate fixation for patients with patella fractures. METHODS: This is a multicentre randomised and prospective clinical trial. A total of 122 patients will be included in the study, and the primary outcome will be the KOOS subscales at 12 months after surgery. CONCLUSIONS: Findings from the present study are expected to advance our understanding of outcome following surgical treatment of patella fractures. FUNDING: This study is funded, in part, by the Novo Nordisk Foundation, Denmark. CLINICALTRIALS: gov ID: NCT04891549.

Stimulating thyrotropin receptor antibodies in early pregnancy.

OBJECTIVES: Thyrotropin-receptor antibodies (TRAb) are used to diagnose Graves' hyperthyroidism in pregnant women. Bioassays provide a measure of thyrotropin-receptor stimulatory antibodies (TSI) specifically. The objective was to measure TSI in pregnant women for establishment of a pregnancy-specific cut-off and comparison with immunoassay measurements of TRAb. METHODS: The retrospective Danish study was performed within the North Denmark Region Pregnancy Cohort (2011-2015) that includes stored biobank samples from early pregnancy (median week 10) with immunoassay measurements of thyroid function parameters and TRAb. TSI were measured in the same samples using the Turbo TSI bioassay (Quidel/Ortho-Clinical Diagnostics) with a recommended cut-off of 0.0241 IU/L in non-pregnant adults. A pregnancy-specific TSI cut-off (95-percentile) was established using Regression on Order Statistics. RESULTS: The established TSI cut-off was 0.0418 IU/L (95 % CI: 0.0417-0.0419). Among women with early pregnancy hyperthyroidism (n=438), 43 women (9.8 %) were TSI positive using the established cut-off, and these women had lower TSH (median 0.008 mIU/L) compared to women with TSI levels below 0.0241 (median TSH 0.040 mIU/L) or in the range from 0.0241 to 0.0418 (median TSH 0.033 mIU/L). Among the 438 women with early pregnancy hyperthyroidism, 22 women were positive for TSI and TRAb, 388 were negative for both, and 28 women were positive for either TSI or TRAb. CONCLUSIONS: This is the first study on TSI measurements in a large cohort of early pregnant women. A pregnancy-specific cut-off for TSI was established and agreement in the classification with immunoassay measurements of TRAb was seen in 94 % of cases.

Changes in acromegaly comorbidities, treatment, and outcome over three decades: a nationwide cohort study.

Objective: To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality. Methods: Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation. Results: Adenoma size and insulin-like growth factor I (IGF-I) levels at diagnosis did not differ significantly between study periods. The risk of being diagnosed with diabetes, heart disease, sleep apnea, joint disease, and osteoporosis increased from the 1990s to the later decades, while the mortality risk declined to nearly half. The risk of cancer did not significantly change. Treatment changed toward the use of more medical therapy, and fewer patients underwent repeat surgeries or pituitary irradiation. A statistically significant increase in the proportion of patients achieving IGF-I normalization within 3-5 years was observed over time (69%, 83%, and 88%). The proportion of patients with three or more deficient pituitary hormones decreased significantly over time. Conclusion: Modern medical treatment regimens of acromegaly as well as increased awareness and improved diagnostics for its comorbidities have led to better disease control, fewer patients with severe hypopituitarism, and declining mortality in the Danish cohort of acromegaly patients. The risk of cancer did not increase over the study period.

Metabolic Sequelae and All-Cause Mortality in Chronic Pancreatitis With and Without Prior Acute Pancreatitis: A Nationwide Population-Based Cohort Study.

INTRODUCTION: The purpose of this study was to investigate the risk of metabolic sequelae and all-cause mortality in a population-based cohort of chronic pancreatitis (CP) patients with and without prior acute pancreatitis (AP). METHODS: We used nationwide health registries to identify all Danish residents (18 years and older) with incident CP from 2000 to 2018. Information on AP/CP diagnoses, metabolic sequelae (post-pancreatitis diabetes mellitus [PPDM], exocrine pancreatic dysfunction, and osteoporosis), and all-cause mortality were obtained from Danish national health registries. CP cases were stratified based on the presence of AP before CP diagnosis. The risk of metabolic sequelae and all-cause mortality was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using multivariate Cox proportional hazards models. RESULTS: A total of 9,655 patients with CP were included. Among patients with CP, 3,913 (40.5%) had a prior AP diagnosis. Compared with patients without a history of AP, patients with prior AP had a decreased risk of death (HR 0.79, 95% CI 0.74-0.84), which was largely confined to the initial period after CP diagnosis. Patients with prior AP had an increased risk of PPDM (HR 1.53, 95% CI 1.38-1.69), which persisted for up to a decade after CP diagnosis. No overall differences in risk were observed for exocrine pancreatic dysfunction (HR 0.97, 95% CI 0.87-1.07) and osteoporosis (HR 0.87, 95% CI 0.74-1.02). DISCUSSION: This nationwide study revealed that most of the patients with CP have no prior episode(s) of AP, indicating that an attack of AP sensitizing the pancreas is not essential for CP development. CP patients with and without prior AP have different risk profiles of PPDM and all-cause mortality.

Maxillary sinus floor augmentation with autogenous bone graft compared with composite grafts: A one-year single-blinded randomized controlled trial.

OBJECTIVE: The objective was to assess the one year implant treatment outcome and patient-related outcome measures (PROMs) following maxillary sinus floor augmentation (MSFA) with autogenous bone graft (ABG) from the zygomatic buttress (control) compared with 1:1 mixture of ABG and anorganic porcine bone mineral (APBM) (Test I) or biphasic bone graft material (BBGM) (Test II). MATERIALS AND METHODS: Sixty healthy patients (34 females, 26 males) were randomly allocated to either control or test groups. Outcome measures included survival of suprastructures and implants, implant stability quotient, health status of peri-implant tissue, peri-implant marginal bone loss, frequency of complications, and PROMs using Oral Health Impact Profile-14 combined with questionnaire assessing patient perception of peri-implant soft tissue, prosthetic solution, implant function, and implant treatment outcome using visual analogue scale. Mean differences were expressed with standard deviation and 95% confidence interval. Level of significance was .05. RESULTS: All suprastructures and implants were well-functioning after one year of functional implant loading. There was no significant difference between control and test groups in any of the applied outcome measures. The implant stability significantly increased from implant placement to abutment connection within all groups (p < .001). High patient satisfaction and significant improvement in oral health-related quality of life was also reported within all groups. CONCLUSION: This study demonstrates that MSFA with composite grafts containing minimal amounts of ABG reveals comparable implant treatment outcomes as compared with ABG alone, after one year of functional implant loading. Extensive ABG harvesting in conjunction with MSFA therefore seems not to be needed.

Can nerve monitoring during radical prostatectomy improve functional outcomes? A randomised trial.

OBJECTIVE: To explore how the use of the ProPep® Nerve Monitoring System (ProPep Surgical, Austin, TX, USA) for intraoperative specific sparing of the pudendal nerve fibres influences postoperative functional outcomes after unilateral nerve-sparing (UNS) or non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We randomised 100 men undergoing UNS or NNS RARP to ProPep nerve monitoring during RARP (intervention) or standard of care RARP (control). Functional outcomes were assessed at 3, 6, and 12 months using the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the International Prostate Symptom Score, the Danish Prostate Symptom Score, the International Index of Erectile Function, the Erection Hardness Scale, and 24-h pad tests. The primary outcome was the difference in ICIQ-SF score between the groups at 12 months. Secondary outcomes included differences in the remaining outcome measures and continence rates at all time points. Continence was defined as the use of no pads and the answer 'Never' to the question: 'How often do you experience urinary incontinence?' or a urine loss of <8 g on the 24-h pad test. RESULTS: A total of 82 patients were included in the per-protocol analysis at 12 months with 41 in each group. At 12 months the mean ICIQ-SF scores were 5.37 (95% confidence interval [CI] 3.71-7.03) and 5.66 (95% CI 4.05-7.27) for the intervention and control groups, respectively (P = 0.8). There were no statistically significant differences in any of the remaining outcomes. However, the continence rate was higher in the intervention group at 6 months (63% vs 44%, P = 0.09). CONCLUSIONS: Intraoperative nerve monitoring did not result in better functional outcomes following UNS or NNS RARP. Larger studies are needed to explore if ProPep can reduce the time to continence after RARP.

Implication of Inflammatory Bowel Disease Diagnosed Before the Age of 18 for Achieving an Upper Secondary Education: A Nationwide Population-Based Cohort Study.

BACKGROUND: Educational achievement may be adversely affected by chronic conditions in childhood and adolescence. This study aimed to examine the effect of being diagnosed with IBD on achievement of an upper secondary education and the influence of disease severity and psychiatric comorbidity. METHODS: This cohort study was based on nationwide Danish administrative registries. We compared a cohort of patients with IBD with a matched population-based cohort. The IBD cohort included patients born between 1970 and 1994 who were diagnosed with IBD (age <18 years). The outcome was achieving an upper secondary education and was analyzed using Cox regression. The impact of disease severity (expressed by surgery or corticosteroid prescriptions) or psychiatric comorbidity within the IBD cohort was assessed using Poisson regression. RESULTS: We identified 3178 patients with IBD (Crohn's disease [CD] n = 1344, ulcerative colitis [UC] n = 1834) and matched them with 28 204 references. The hazard ratio of achieving an upper secondary education was 1.14 (95% confidence interval, 1.07-1.21) for CD and 1.16 (95% confidence interval, 1.10-1.23) for UC. In the IBD cohort, having surgery, a steroid prescription, or a comorbid psychiatric condition was associated with a lower chance of achieving an upper secondary education. CONCLUSION: Being diagnosed with IBD before 18 years of age increased the chance of achieving an upper secondary education. However, patients with more severe disease or psychiatric comorbidity were at higher risk of not achieving an upper secondary education than patients with milder disease.

Multistate Model of the Natural History of Inflammatory Pancreatic Diseases: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: Understanding the nature of inflammatory pancreatic diseases is essential for planning health care system requirements and interventions. The aim of this study was to quantify the trajectories of inflammatory pancreatic diseases and their association with pancreatic cancer in a population-based setting. METHODS: National health registries were used to identify all Danish residents (18 years or older) in the period from 2000 through 2018 with incident cases of acute pancreatitis (AP), recurrent acute pancreatitis (RAP), chronic pancreatitis (CP), and pancreatic cancer. We used a multistate model to examine transitions from a healthy state to intermediate states of acute pancreatic inflammation (AP and RAP) to chronic states (CP and pancreatic cancer) and, ultimately, death. Results were reported as transition incidence rates per 1000 person-years with 95% CIs. RESULTS: There were 4,663,864 individuals included (mean age, 46 years; 51% were women). During a mean follow-up of 16.8 years, 31,396 individuals were diagnosed with incident AP, 5546 with RAP, 8898 with CP, and 18,182 with pancreatic cancer. The cumulative incidence of pancreatitis (acute and chronic) during the study period was 0.80% (95% CI, 0.79%-0.80%). The transition incidence rates to CP were 12.1 (95% CI, 8.1-18.1) from AP, 46.8 (95% CI, 31.6-69.3) from RAP, and 0.07 (95% CI, 0.04-0.13) from a healthy state. Similar patterns were observed for transitions to pancreatic cancer. Most patients diagnosed with CP (64.2%) and pancreatic cancer (96.4%) transitioned directly from a healthy state. Among patients with pancreatitis, 41.0% (95% CI, 40.5%-41.5%) died during follow-up. CONCLUSIONS: The study findings revealed an increased risk of CP and pancreatic cancer in patients with a history of AP. However, most patients with CP and pancreatic cancer transitioned directly from a healthy state.

Bone regeneration after maxillary sinus floor augmentation with different ratios of autogenous bone and deproteinized bovine bone mineral an in vivo experimental study.

OBJECTIVE: Test the hypothesis of no difference in bone regeneration after maxillary sinus floor augmentation (MSFA) with different ratios of iliac or mandibular autogenous bone (AB) graft and deproteinized bovine bone mineral (DBBM). MATERIALS AND METHODS: Forty minipigs were randomly allocated to bilateral MSFA using: (A) 100% AB, (B) 75% AB and 25% DBBM, (C) 50% AB and 50% DBBM, (D) 25% AB and 75% DBBM, or (E) 100% DBBM. The animals were euthanized 12 weeks after surgery. Percentage of bone, non-mineralized tissue, and residual DBBM were estimated by histomorphometric analysis in a randomly selected region of interest and summarized as mean percentage with 95% confidence interval (CI). RESULTS: Mean percentage of bone following MSFA with iliac or mandibular AB graft was: (A) 55.5% and 64.2%, (B) 60.3% and 61.6%, (C) 54.4% and 52.1%, (D) 51.8% and 53.1%, and (E) 47.6%, respectively. There was a significant trend toward a higher percentage of bone, with a higher ratio of AB within the graft (p < .01), regardless of the origin of AB graft (iliac or mandible). CONCLUSIONS: The hypothesis was rejected since percentage of bone was significantly increased with larger proportions of AB within the graft. Consequently, AB or a mixture of AB and diminutive quantities of DBBM seem to be the preferred graft for MSFA based solely on histomorphometric assessment. However, it should be emphasized that newly formed bone and residual AB graft particles could not be distinguished by the applied histologic procedure.

Instantaneous wave free ratio vs. fractional flow reserve and 5-year mortality: iFR SWEDEHEART and DEFINE FLAIR.

BACKGROUND AND AIMS: Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischaemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038). METHODS: Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk, and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp, College Station, TX, USA). RESULTS: In total, iFR and FFR-guided revascularization was performed in 2254 and 2257 patients, respectively. Revascularization was more often deferred in the iFR group [n = 1128 (50.0%)] vs. the FFR group [n = 1021 (45.2%); P = .001]. In the iFR-guided group, the number of deaths, MACE, unplanned revascularization, and MI was 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.04; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32]. CONCLUSIONS: Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups.

Maxillary sinus membrane elevation and coagulum compared with maxillary sinus floor augmentation and a composite graft: A 1-year single-blinded randomized controlled trial.

OBJECTIVE: The aim was to evaluate the 1-year implant outcome and patient-related outcome measures (PROMs) after maxillary sinus membrane elevation and coagulum (test) compared with maxillary sinus floor augmentation and a 1:1 ratio of autogenous bone graft from the buccal antrostomy and deproteinised porcine bone mineral (DPBM) (control). MATERIALS AND METHODS: Forty patients (30 female, 10 male) with a mean age of 50 years (range 25-71 years) and an alveolar ridge height between 4 and 7 mm were randomly allocated to test or control. Outcome measures included survival of suprastructures and implants, implant stability quotient, health status of the peri-implant tissue, peri-implant marginal bone loss, frequency of complications and PROMs using Oral Health Impact Profile-14 combined with questionnaires assessing patient's perception of the peri-implant soft tissue, implant crown, function of the implant, and total implant treatment outcome using visual analogue scale. Mean differences were expressed with standard deviation and 95% confidence interval. Level of significance was 0.05. RESULTS: All suprastructures and implants were well-functioning after 1-year of functional implant loading. No significant difference in any of the applied outcome measures was observed between test and control. Both treatments revealed high patient satisfaction scores and significant improvement in oral health-related quality of life. CONCLUSION: There were no significant differences in implant outcome and PROMs between test and control, after 1-year of functional implant loading. Neither of the treatments can therefore be considered better than the other. Thus, long-term randomized controlled trials are needed before definitive conclusions can be provided about the two treatment modalities.

Horizontal Alveolar Ridge Augmentation with Xenogenic Block Grafts Compared with Autogenous Bone Block Grafts for Implant-retained Rehabilitation: a Systematic Review and Meta-Analysis.

Objectives: The objective of the present systematic review and meta-analysis was to test the 0-hypothesis of no difference in implant treatment outcome after horizontal alveolar ridge augmentation with xenogenic block compared with autogenous bone block. Material and Methods: A literature search was conducted using PubMed, Embase and Cochrane Library databases in combination with a hand-search of relevant journals until 25th of January 2022. Comparative and non-comparative studies evaluating horizontal alveolar ridge augmentations with xenogenic blocks were included. Quality and risk of bias were evaluated by Cochrane Collaboration's revised tool and Newcastle-Ottawa scale. Results: Meta-analysis revealed no statistically significant difference in implant survival rate after more than 6 months of functional implant loading (P = 0.71), no difference in alveolar ridge width (P = 0.07) or gain of alveolar ridge width at re-entry (P = 0.13). Non-comparative studies revealed moderate to high short-term implant survival rate and gain in alveolar ridge width, however, complications including dehiscences, graft exposure and graft failure were observed in several studies. Conclusions: No significant difference could be identified in short-term implant treatment outcome following horizontal alveolar ridge augmentation using xenogenic block compared with autogenous bone block with the limited data available. A high incidence of healing complications and implant failures necessitates further investigation, as well as long-term results on implant survival rate.

Low- versus standard- pneumoperitoneum in patients undergoing robot-assisted radical prostatectomy: a randomised, triple-blinded study.

OBJECTIVE: To investigate the effectiveness and impact of low-pressure pneumoperitoneum (Pnp) on postoperative quality of recovery (QoR) and surgical workspace (SWS) in patients with prostate cancer undergoing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A randomised, triple-blinded trial was conducted in a single centre in Denmark from March 2021 to January 2022. A total of 98 patients with prostate cancer undergoing RARP were randomly assigned to either low-pressure Pnp (7 mmHg) or standard-pressure Pnp (12 mmHg). Co-primary outcomes were postoperative QoR measured via the QoR-15 questionnaire on postoperative Day 1 (POD1), POD3, POD14, and POD30, and SWS assessed intraoperatively by a blinded assessor (surgeon) via a validated SWS scale. Data analysis was performed according to the intention-to-treat principle. RESULTS: Patients who underwent RARP at low Pnp pressure demonstrated better postoperative QoR on POD1 (mean difference = 10, 95% confidence interval [CI] 4.4-15.5), but no significant differences were observed in the SWS (mean difference = 0.25, 95% CI -0.02 to 0.54). Patients allocated to low-pressure Pnp experienced statistically higher blood loss than those in the standard-pressure Pnp group (mean difference = 67 mL, P = 0.01). Domain analysis revealed significant improvements in pain (P = 0.001), physical comfort (P = 0.007), and emotional state (P = 0.006) for patients with low-pressure Pnp. This trial was registered at ClinicalTrials.gov, NCT04755452, on 16/02/2021. CONCLUSION: Performing RARP at low Pnp pressure is feasible without compromising the SWS and improves postoperative QoR, including pain, physical comfort, and emotional state, compared to the standard pressure.

Radiographic outcome after maxillary sinus floor augmentation with allogeneic adipose tissue-derived stem cells seeded on deproteinized bovine bone mineral. A randomized controlled experimental study.

The objective was to test the hypothesis of no difference in radiographic outcome after maxillary sinus floor augmentation (MSFA) with allogeneic adipose tissue-derived stem cells (ASCs) seeded on deproteinized bovine bone mineral (DBBM) (test) compared with excipient on DBBM (control). Eighteen minipigs were assigned into three groups of six animals and euthanised after one month (T1), two months (T2), and four months (T3), respectively. Each maxillary sinus was randomly allocated to either test or control with an equal volume of graft. Computed tomography scans (CTs) after MSFA (T0) were compared with CTs after euthanasia to evaluate graft volume (GV) changes and bone density (BD) using three-dimensional measurements and Hounsfield units. GV was larger in test compared with control at T1 (P = 0.046), whereas GV was larger in control compared with test at T3 (P = 0.01). BD increased from T0 to T1-T3 (P < 0.001) with both treatments. Higher BD was observed in control compared with test at T3 (P = 0.01), while no significant difference was observed at T1 and T2. Conclusively, the present study demonstrate that allogeneic ASCs seeded on DBBM in conjunction with MSFA seemed not to improve the radiographic outcome compared with excipient on DBBM. However, radiological outcomes need to be supplemented by bone histomorphometry before definitive conclusions can be provided about the beneficial use of allogeneic ASCs seeded on DBBM in conjunction with MSFA compared with DBBM alone.

Maternal alcohol consumption and the risk of miscarriage in the first and second trimesters: A systematic review and dose-response meta-analysis.

INTRODUCTION: According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response meta-analysis, we aimed to examine the association between alcohol consumption and binge drinking and the risk of miscarriage in the first and second trimesters. MATERIAL AND METHODS: The literature search was conducted in MEDLINE, Embase and the Cochrane Library in May 2022, without any language, geographic or time limitations. Cohort or case-control studies reporting dose-specific effects adjusting for maternal age and using separate risk assessments for first- and second-trimester miscarriages were included. Study quality was assessed using the Newcastle-Ottawa Scale. This study is registered with PROSPERO, registration number CRD42020221070. RESULTS: A total of 2124 articles were identified. Five articles met the inclusion criteria. Adjusted data from 153 619 women were included in the first-trimester analysis and data from 458 154 women in the second-trimester analysis. In the first and second trimesters, the risk of miscarriage increased by 7% (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96-1.20) and 3% (OR 1.03, 95% CI 0.99-1.08) for each additional drink per week, respectively, but not to a statistically significant degree. One article regarding binge drinking and the risk of miscarriage was found, which revealed no association between the variables in either the first or second trimester (OR 0.84 [95% CI 0.62-1.14] and OR 1.04 [95% CI 0.78-1.38]). CONCLUSIONS: This meta-analysis revealed no dose-dependent association between miscarriage risk and alcohol consumption, but further focused research is recommended. The research gap regarding miscarriage and binge drinking needs further investigation.

Phagocyte-related S100 proteins and cytokines in acute lymphoblastic leukemia and their prognostic value.

In this retrospective cohort study, we evaluated the level of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of cytokines in 128 children with pre-B ALL and 22 with T-ALL. The biomarkers were evaluated at diagnosis and during antileukemic therapy (day 29 and after six months) and we evaluated their correlation with basic laboratory values. Further, for the children with pre-B ALL, we evaluated whether the biomarkers could predict the outcome of ALL expressed as minimal residual disease (MRD), relapse, and death.The levels of S100A9, S100A12, IL-1beta, IL-12p70, IL-13, IL-17, IL-18, and MPO serum levels increased significantly as chemotherapy was initiated. The difference was most pronounced for S100A9 and S100A12, which had strong positive correlations with the neutrophil counts. In contrast, TNF-alpha, IL-6, IL-10, CCL-2, MMP-3, and CD25 serum levels decreased after chemotherapy. Although none of these biomarkers appear to be an independent predictor of outcomes, in predictive models with MRD as the outcome, AUC increased from 76% (95% CI 68-84%) when using initial risk group stratification alone to 83% (95% CI 73-91%) in a multivariate predictive model including initial risk group stratification and the biomarkers S100A12, TNF-alpha, and IL-10.

Lower or higher oxygenation targets for acute Hypoxaemic respiratory failure: Protocol for an individual patient data meta-analysis.

BACKGROUND: Supplemental oxygen therapy is central to the treatment of acute hypoxaemic respiratory failure, a condition which remains a major driver for morbidity and mortality in intensive care. Despite several large randomised clinical trials comparing a higher versus a lower oxygenation target for these patients, significant differences in study design impede analysis of aggregate data and final clinical recommendations. METHODS: This paper presents the protocol for conducting an individual patient data meta-analysis where full individual patient data according to the intention-to-treat principle will be pooled from the HOT-ICU and HOT-COVID trials in a one-step procedure. The two trials are near-identical in design. We plan to use a hierarchical general linear mixed model that accounts for data clustering at a trial and site level. The primary outcome will be 90-day all-cause mortality while the secondary outcome will be days alive without life-support at 90 days. Further, we outline 14 clinically relevant predefined subgroups which we will analyse for heterogeneity in the intervention effects and interactions, and we present a plan for assessing the credibility of the subgroup analyses. CONCLUSION: The presented individual patient data meta-analysis will synthesise individual level patient data from two of the largest randomised clinical trials on targeted oxygen therapy in intensive care. The results will provide a re-analysis of the intervention effects on the pooled intention-to-treat populations and facilitate subgroup analyses with an increased power to detect clinically important effect modifications.

Extended Right-Sided Colon Resection Does Not Reduce the Risk of Colon Cancer Local-Regional Recurrence: Nationwide Population-Based Study From Danish Colorectal Cancer Group Database.

BACKGROUND: It is controversial whether extensive resection of right-sided colon cancer confers oncological benefits. OBJECTIVE: The aim of this study was to evaluate short- and long-term outcomes of extended surgical removal of the mesocolon compared to the conventional approach. DESIGN: This was a retrospective population-based study. SETTING: Study is based on a prospectively maintained Danish Colorectal Cancer Group database. MAIN OUTCOME MEASURES: Primary outcome measures included local-regional recurrence in patients who underwent curative resection for right-sided colon cancer and 30-day postoperative complications. Distant metastasis, unplanned intraoperative adverse events, and 30- and 90-day postoperative mortality were also investigated. Patients who had palliative or compromised resection, emergency surgery, or neoadjuvant chemotherapy were excluded. RESULTS: Of the 12,855 patients with resection of right-sided colon cancer retrieved, 1151 underwent extended right hemicolectomy. Patients who had extended right hemicolectomy were younger males with lower ASA scores, were operated on by colorectal surgeons using a laparoscopic approach, and had a significantly higher number of harvested lymph nodes. The rate of local-regional recurrence was 1.1% (136/12,855), with no difference between conventional right hemicolectomy and extended right hemicolectomy (OR, 1.7; 95% CI, 0.63-2.18). Postoperative medical complications were significantly higher in extended right hemicolectomy even after adjusting for age, comorbidity, access to the abdomen, and other covariates (OR, 1.26; 95% CI, 1.01-1.58). No significant difference was noticed between conventional right hemicolectomy and extended right hemicolectomy in the rates of distant metastasis, unplanned intraoperative adverse events, and mortality. LIMITATIONS: Because it is a register-based study, underreporting cannot be excluded. Extended right hemicolectomy, as defined in this study, does not reflect the extent of lymphatic dissection performed during the surgery. CONCLUSIONS: This large population-based register study showed no difference in local-regional recurrence of right-sided colon cancer between conventional and extended right hemicolectomy with mesenteric resection and ligation of the middle colic vessels. Extended resection was associated with higher rates of postoperative complications. See Video Abstract at http://links.lww.com/DCR/B907 . LA RESECCIN AMPLIADA DEL COLON DERECHO NO REDUCE EL RIESGO DE RECURRENCIA LOCALREGIONAL DEL CNCER DE COLON ESTUDIO POBLACIONAL A NIVEL NACIONAL DE LA BASE DE DATOS DEL GRUPO DANS DE CNCER COLORRECTAL: ANTECEDENTES:Es aun un tema controversial si la resección ampliada del cáncer de colon del lado derecho confiere beneficios oncológicos.OBJETIVOS:El objetivo de este estudio fue examinar los resultados a corto y largo plazo de la resección quirúrgica ampliada del mesocolon en comparación con el enfoque convencional.DISEÑO:Este fue un estudio poblacional de tipo retrospectivo basado en una base de datos del Grupo Danés de Cáncer Colorrectal mantenida de manera prospectiva.AJUSTES:La medida de resultado primaria fue la recurrencia local-regional en pacientes sometidos a resección curativa por cáncer de colon del lado derecho y las medidas de resultado secundarias fueron las complicaciones posoperatorias a los 30 días. También fueron investigadas las metástasis a distancia, los eventos adversos intraoperatorios no planificados y la mortalidad posoperatoria a los 30 y 90 días. Se excluyeron los pacientes sometidos a resección paliativa o comprometida, cirugía de urgencia y quimioterapia neoadyuvante.RESULTADOS:De los 12.855 pacientes recuperados y sometidos a resección de cáncer de colon del lado derecho, 1151 fueron sometidos a hemicolectomía derecha ampliada. Los pacientes sometidos a hemicolectomía derecha ampliada fueron varones más jóvenes con puntuaciones ASA más bajas, operados por cirujanos colorrectales, utilizando la vía laparoscópica, y tuvieron un número significativamente mayor de ganglios linfáticos extraídos. La tasa de recidiva local-regional fue del 1,1% (136 / 12.855) sin diferencia entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada (OR 1,7 IC 95% 0,63-2,18). Las complicaciones médicas post operatorias fueron significativamente mayores en la hemicolectomía derecha ampliada incluso después del ajuste por edad, comorbilidad, acceso al abdomen y otras covariables (OR 1,26; IC 95% 1,01-1,58). No se observaron diferencias significativas entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada con respecto a las tasas de metástasis a distancia, eventos adversos intraoperatorios no planificados y mortalidad.LIMITACIONES:Es un estudio basado en registros, por lo tanto, no se puede excluir la sub notificación. La hemicolectomía derecha ampliada como se define en este estudio no refleja la extensión de la disección linfática realizada durante la cirugía.CONCLUSIONES:Este gran estudio basado en el registro poblacional no mostró diferencias en la recurrencia local-regional del cáncer de colon del lado derecho entre la hemicolectomía derecha convencional y ampliada con resección mesentérica y ligadura de los vasos cólicos medios. La resección ampliada se asoció con tasas más altas de complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B907 . (Traducción-Dr. Osvaldo Gauto ).