Short-term Follow-up Period Research Articles

Prescribing Pattern and Safety Profile of Biological Agents for Psoriasis in Real-World Practice: A Four-Year Calabrian Pharmacovigilance Analysis

Background: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. Methods: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. Results: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. Conclusions: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests.

The Long-Term Clinical and Radiographic Outcomes of Cerclage Cable Fixation for Displaced Acetabular Fractures Using a Posterior Approach: A Retrospective Cohort Study.

Background and Objectives: Cerclage cable fixation with 2 mm multiple-braided cables for displaced acetabular fractures has shown good midterm functional and radiographic outcomes. We retrospectively evaluated the clinical and radiographic outcomes of cerclage cable fixations over ten years. Materials and Methods: We extracted data for patients who underwent cerclage cable fixation for acetabular fractures at a single institution from 2007 to 2012. We adopted this procedure for acetabulum fractures with posterior column fractures. Postoperative reduction quality, complications, reoperations, and Japanese Orthopedic Association (JOA) hip objective functional scores were analyzed. Postoperative reduction quality was classified using plain radiography and computed tomography. Results: We evaluated nine patients with a mean follow-up period of 14.1 ± 2.6 years (range: 10.8-18.1 years). The mean age was 47.1 ± 15.5 years old (range: 28-74 years); the mean injury severity score was 13.6 ± 4.7 (range: 9-22). The most frequent type of fracture was a both-column fracture. Anatomical reduction quality was achieved in five cases. Four patients had hip osteoarthritis at the last follow-up; among them, one patient had worsening hip arthritis > 5 years after surgery, and one patient developed osteoarthritis > 10 years after surgery. Their postoperative reduction quality was worse than their anatomical reduction quality, and both engaged in physical labor. None of the patients underwent revision total hip arthroplasty. The mean JOA hip score was 90.9 ± 7.9 (range: 74-100); seven patients scored >90 at the last follow-up. Conclusions: Cerclage cable fixation showed satisfactory postoperative reductions and favorable long-term clinical outcomes. Long-term follow-up might be necessary for patients whose postoperative reduction is not anatomical to detect late occurrence of hip osteoarthritis, even if osteoarthritis is not evident during short-term follow-up periods.

Associations between type of bariatric surgery and obstructive sleep apnoea, employment outcomes, and body image satisfaction: A systematic review and meta-analysis.

Bariatric surgery has been shown to provide significant patient benefits in terms of weight loss and mitigation of obesity linked co-morbidities, as well as providing improvements in occupational productivity and patient quality of life. However, the choice of which bariatric surgery procedure provides the most patient benefit in each of these cases is still in question. In this study we provide a systematic review, with the objective of evaluating associations between different bariatric surgery procedures and mitigation of obesity linked co-morbidities, improvement in occupational productivity, and patient quality of life, concentrating on three areas: obstructive sleep apnoea (OSA), employment prospects and body image. The CINAHL, PubMed, Web of Science, and CENTRAL databases were searched for eligible studies. Summary risk ratio (RR) and 95% confidence intervals were estimated using random-effects models. Thirty-three studies were included in this review, including 29 cohort studies and 4 randomised clinical trials (RCTs). Pooled analysis of the observational studies showed significantly lower OSA remission in sleeve gastrectomy (SG) compared to Roux-en-Y gastric bypass (RYGB) across both short-term (1-2 years) and longer-term (3+ years) follow-up periods, (RR=0.91, 95% CI = 0.84-0.99, p=0.02 and RR=0.88, 95% CI = 0.65-0.99, p=0.03 respectively). In contrast, a metanalysis of the RCT studies found no difference in OSA remission between SG and RYGB (RR=1.01, 95% CI = 0.81-1.25, p=0.93). An analysis of four studies showed significantly higher OSA remission for SG versus Adjustable Gastric Band (RR=1.83, 95% CI = 1.57-2.14, p<0.001). No significant difference was observed regarding improvement in employment status between SG and RYGB (RR=0.77, 95% CI = 0.32-1.87, p = 0.57). A narrative synthesis of studies on body image reported no significant differences between body image scores and surgery types. This review found significantly lower OSA remission in SG as compared to RYGB across different follow up periods, while no significant statistical difference was observed in RCTs studies. Further studies are recommended to assess the effectiveness of the various bariatric surgeries in relation to improving employment status and body image, where primary studies are lacking.

Treatment of intracranial aneurysms using the Tubridge flow diverter.

The Tubridge flow diverter (TFD) was recently developed to treat intracranial aneurysm (IA). In this study, we aimed to assess the safety and efficacy of this novel device. A retrospective cohort of consecutive patients with IA was recruited between June 2017 and February 2022. The studied outcomes were perioperative complications, clinical quality of life, and angiographic IA occlusion. Multivariate logistic regression was performed to explore the potential predictors of perioperative stroke events and IA occlusion. A comprehensive literature review was conducted across five databases for evidence synthesis. Among the patients with IA in our cohort, 144 underwent successful TFD implantation. Postoperative stroke was observed in 11 (7.6%) patients, and 130 (90.3%) patients were discharged with modified Rankin scales (mRS) of ≤2. In the last clinical follow-up (mean, 16.9months), 96.6% of the patients reported a satisfactory quality of life (mRS ≤2). IA occlusion was observed in 84.6% of the patients at the last angiographic follow-up (mean, 10.4months). Aneurysmal subarachnoid hemorrhage [odds ratio (OR), 6.98; 95% confidence interval (CI), 1.11-43.91] and giant IA (OR, 5.63; 95% CI, 1.15-27.48) were associated with perioperative stroke events. The evidence synthesis found high rates of satisfactory quality of life (rate, 98.8%; 95% CI, 97.1-99.9%) and IA obliteration (rate, 78.5%; 95% CI, 74.0-82.7%) after TFD treatment. The pooled complication rate was 13.6% (95% CI, 10.9-16.5%). This study identified a high rate of IA occlusion in patients who received TFD treatment. These patients also reported a satisfactory quality of life. Further studies in larger prospective cohorts with longer follow-up periods are warranted to verify our findings. Key message What is already known on this topic Flow diverter (FD) devices are an optimal tool to modify hemodynamics and treat intracranial aneurysms (IAs). However, the safety and efficacy of a novel self-expanding FD, namely the Tubridge flow diverter (TFD), remain to be fully established owing to the short-term follow-up periods and limited sample size of existing studies. What this study adds In our cohort of patients who received TFD treatment, 96.6% of patients reported satisfactory quality of life at the last clinical follow-up (mean, 16.9months); and 84.6% of IAs were successfully occluded at the last angiographic follow-up (mean, 10.4months). Our comprehensive review and evidence synthesis of existing studies on TFD found high rates of satisfactory quality of life (98.8%; 97.1-99.9%) and IA obliteration (78.5%; 74.0-82.7%). How this study might affect research, practice or policy TFD demonstrated satisfactory performance in the treatment of IAs in our cohort. Studies with larger prospective cohorts and longer follow-up periods are warranted to further investigate this promising novel approach.

5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data

BackgroundIncreasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. MethodsThe MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. ResultsOverall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58–1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87–1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. ConclusionsThe use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Contemporary Incidence of Cognitive Impairment or Dementia in Patients undergoing Coronary Artery Bypass Grafting: A Systematic Review and Meta-analysis.

Despite the high prevalence of cognitive impairment or dementia post coronary artery bypass grafting (CABG), the incidence of cognitive impairment or dementia post-CABG in contemporary practice is currently unclear. Therefore, this paper aims to investigate the incidence and associated risk factors of cognitive impairment or dementia in patients post-CABG. A systematic search across three databases (PubMed, SCOPUS and Embase) was conducted for studies published in or after 2013 that reported cognitive impairment or dementia post-CABG. Subgroup analyses and meta-regression by risk factors were performed to determine their influence on the results. This analysis included 23 studies with a total of 2620 patients. The incidence of cognitive impairment or dementia less than one month, two to six months, and more than twelve months post-CABG was 35.96% (95%CI: 28.22-44.51, I2=87%), 21.33% (95%CI: 13.44-32.15, I2=88%) and 39.13% (95%CI: 21.72-58.84, I2=84%), respectively. Meta-regression revealed that studies with more than 80% of the cohort diagnosed with hypertension were significantly associated with incidence of cognitive impairment or dementia less than one-month post-CABG. This meta-analysis demonstrates a high incidence of cognitive impairment or dementia in patients post-CABG in contemporary practice, particularly less than one month post-CABG. We found that hypertension was a significant risk factor in the short term (less than one month) follow-up period for cognitive impairment or dementia post-CABG. Future research should be done to assess strategies to reduce cognitive impairment post-CABG. .

Home based cardiac rehabilitation: A retrospective cohort analysis on all-cause mortality and hospital readmission rates across sexes and races

ObjectiveStudies have shown that both home-based cardiac rehabilitation (HBCR) and center-based cardiac rehabilitation (CBCR) exhibit comparable efficacy in reducing mortality during short-term follow-up periods of up to 12 months. However, research on sex- and race-specific outcomes associated with HBCR is limited. This study examines all-cause mortality and hospital readmission among patients referred to HBCR, with stratification by sex and race. MethodsThis Kaiser Permanente Southern California (KPSC) retrospective cohort study followed 6,868 patients from HBCR referral until death, disenrollment, or December 31, 2021. There were 3,835 HBCR graduates, 722 non-graduates, and 2,311 non-enrolled patients. Cox models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) comparing 1) HBCR graduates vs. non-enrolled, and 2) HBCR graduates vs. non-graduates, stratified by sex and race. Differential outcomes among strata were analyzed using Kaplan-Meier curves. ResultsAmong the 6,868 patients referred to HBCR, 4693 (68.3 %) were male, 2,175 (31.7 %) female, 870 (12.7 %) Asian/Pacific Islander, 731 (10.6 %) African American, 1,612 (23.6 %) Hispanic/Latino, and 3,646 non-Hispanic White (53.1 %). Over a mean follow-up period of 2.28 years, HBCR graduates, compared to patients who did not enroll in HBCR, had overall significantly lower risks of all-cause mortality and hospitalization. These results remained significant with stratification by sex and race. Compared to HBCR non-graduates, HBCR graduates overall had significantly lower risks of all-cause mortality and hospitalization. In the same comparison, mortality risk was significantly reduced for male and White patients; risk of hospital readmission was significantly reduced in both sexes, African American, and White patients. Among HBCR graduates, no significant differences in all-cause mortality or hospital readmission were observed across sexes and races. ConclusionHBCR participation is associated with reduction of all-cause mortality and hospital readmission rates across sexes and races. Notably, we observed benefits at varying levels of engagement, which suggests that even partial completion of HBCR is associated with risk reduction. Among HBCR graduates, we found similar outcomes across sexes and races, which suggests that the program can be effective among diverse patient groups.

Improving Sarcoma Outcomes: Target Trial Emulation to Compare the Impact of Unplanned and Planned Resections on the Outcome.

This study follows the Target Trial Emulation (TTE) framework to assess the impact of unplanned resections (UEs) and planned resections (PEs) of sarcomas on local recurrence-free survival (LRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Sarcomas, malignant tumors with mesenchymal differentiation, present a significant clinical challenge due to their rarity, complexity, and the frequent occurrence of UEs, which complicates effective management. Our analysis utilized real-world-time data from the Swiss Sarcoma Network, encompassing 429 patients, to compare the impact of UEs and PEs, adjusting for known prognostic factors through a multivariable Cox regression model and propensity score weighting. Our findings reveal a significantly higher risk of local recurrence for UEs and a short-term follow-up period that showed no marked differences in MFS, CSS, and OS between the UE and PE groups, underlining the importance of optimal initial surgical management. Furthermore, tumor grade was validated as a critical prognostic factor, influencing outcomes irrespective of surgical strategy. This study illuminates the need for improved referral systems to specialized sarcoma networks to prevent UEs and advocates for the integration of TTE in sarcoma research to enhance clinical guidelines and decision-making in sarcoma care. Future research should focus on the prospective validations of these findings and the exploration of integrated care models to reduce the incidence of UEs and improve patient outcomes.

Retrospective Analysis of the Clinical Usefulness of a Strut-Adjusted Volume Implant in a Single Center.

Reports demonstrating the effectiveness and safety of strut-adjusted volume implants (SAVI) in Japan are limited. Therefore, this study aimed to compare the treatment outcomes of SAVI and whole-breast irradiation (WBI) at a single facility. Data were retrospectively extracted from the medical records of patients treated with SAVI or WBI following partial mastectomy (Bp). Patients undergoing Bp, sentinel lymph node biopsy, and SAVI spacer insertion followed by brachytherapy with the SAVI device were compared to those followed with WBI. Local recurrence was assessed annually by physical examination, bilateral mammography, and breast ultrasonography. The SAVI and WBI groups comprised 53 and 113 patients, with a median age of 55 and 52 years, respectively; among them, 47 and 91 patients had a pathological tumor diameter ≤2 cm and six and 22 had a pathological tumor diameter >2 cm, respectively. Recurrence events, acute adverse events, and late adverse events were observed in the SAVI and WBI groups in 1 and 3 (p = 0.726), 24 and 79 (p = 0.01), and 24 and 18 patients (p = 0.00002), respectively, with median observation periods of 60.0 and 47.8 months, respectively. All adverse events were grades 1-2, with dermatitis being the most common in the acute phase. In the late phase, pigmentation was common in both groups. The local recurrence rate does not differ between SAVI and WBI within the relatively short-term follow-up period. Longer follow-up is required to confirm our results in the Japanese population.

Safety and Effectiveness of Acellular Dermal Matrix in Breast-Conserving Surgery for Breast Cancer: A Single-Institution Study

Purpose: As breast-conserving surgery (BCS) has become the most common type of breast surgery, oncoplastic BCS has developed in response to improve cosmetic outcomes. Acellular dermal matrix (ADM) has been used as an adjunct to enhance cosmetic outcomes in partial breast reconstruction. This study aimed to evaluate postoperative complications, cosmetic satisfaction, and oncologic safety over a short-term follow-up period. Methods: This retrospective study included 26 patients who underwent BCS at Myongji Hospital between April 2019 and April 2021. All procedures were performed by three surgeons. We reviewed demographic data, histologic grades, tumor-node-metastasis stages, treatment modalities, and survival data based on patient medical records. Results: Of the 26 total patients, 5 developed seromas, which was the most common complication, and one patient experienced red breast syndrome. The incidence of complications per surgeon was less than 25%. The mean satisfaction score for the cosmetic outcome on a 10-point scale was 7.6 ( ± 2.1) as scored by patients and 8.8 ( ± 0.9) as scored by surgeons. Responses regarding cosmetic satisfaction revealed no significant differences among surgeons (<i>p</i>= 0.444). Of the 26 patients, four were lost to follow-up, and the mean follow-up period was 35.2 months. Two patients experienced recurrence, both of whom had regional recurrence with no local recurrence. Conclusion: ADM replacement is a favorable alternative to oncoplastic BCS, in terms of the ease of surgical procedures, minimal complications, and low rates of local recurrence.

Sustainable improvement in upstream and downstream outcomes for intubated patients three years after an airway-based educational intervention in a low-resource pediatric intensive care unit

ObjectiveTo determine whether implementation of an education-based intervention can sustainably improve upstream and downstream outcomes in intubated patients in a pediatric intensive care unit (PICU) in a low-resource country. DesignQuality improvement study comparing airway-related morbidity in two previously studied patient cohorts pre-intervention (Epoch 1) and immediately post-intervention (Epoch 2) with a third cohort thirty-six months post-intervention (Epoch 3). SettingPICU of the largest public children's hospital in El Salvador. Patients147 patients under 18 years requiring intubation and mechanical ventilation (MV) met inclusion criteria in the long-term follow-up period and were consecutively sampled without exclusion (Epoch 3) (compared to 98 previously studied patients in the short-term follow-up period (Epoch 2)). InterventionA low-cost, education-based intervention to close knowledge gaps, improve communication among PICU doctors, nurses, and respiratory therapists, and optimize patient outcomes. Measurements and main resultsThe primary outcome measure was change in unplanned extubation (UE) between Epochs 2 and 3. Other outcomes included use of cuffed endotracheal tubes (ETT), rate of elective ETT change and days of MV. The 17 % decrease in UE previously reported for Epoch 2 was sustained in Epoch 3. There was a statistically significant increase in use of cuffed ETT from 35.7 % in Epoch 2–55.1 % in Epoch 3 (p = 0.003, z-score −2.99). There was also a statistically significant mean difference in rate of elective ETT change per 100 MV days from Epoch 2 to Epoch 3 of 1.7 (p = 0.007; 95 % CI 0.15–0.84). There was no change in MV days from Epoch 2 to Epoch 3 (p-value 0.764; 95 % CI -1.48–2.02). Beyond these quantifiable results, many unanticipated practice changes were observed three years after the initial intervention. ConclusionsSustained improvement in upstream and downstream outcomes (UE, cuffed ETT use, elective ETT change) for intubated patients in a low-resource PICU were observed three years after a low-cost, low-touch, education-based intervention.

Hemispherectomy at The Hospital for Sick Children: expanded indications and lessons learned over 35 years

OBJECTIVE Functional hemispherectomy is an effective surgical intervention for select patients with drug-resistant epilepsy. The last several decades have seen dramatic evolutions in preoperative evaluation, surgical techniques, and postoperative care. Here, the authors present a retrospective review of the medical records of 146 children who underwent hemispherectomy between 1987 and 2022 at The Hospital for Sick Children, providing a unique overview of the evolution of the procedure and patient outcomes over 35 years. METHODS The medical records of all children who underwent hemispherectomy at The Hospital for Sick Children between 1987 and 2022 were reviewed. Demographic information, preoperative clinical features, short-term and long-term seizure outcomes, and details regarding postoperative complications were recorded. RESULTS The seizure outcomes of 146 children were analyzed. There were 68 females and 78 males with a mean age of 5.08 years, 123 of whom demonstrated seizure freedom (Engel class IA) in the short-term postoperative follow-up period and 89 in the long term. The effectiveness of hemispherectomy in achieving long-term seizure control has improved over time (β = 0.06, p < 0.001). Factors associated with overall seizure freedom included younger age at the time of hemispherectomy and stroke as the etiology of seizures, as well as complete disconnection during the first surgery. Additionally, the etiologies of epilepsy for which hemispherectomy is performed have expanded over time, while complication rates have remained unchanged. CONCLUSIONS Hemispherectomy is an increasingly effective treatment for certain cases of drug-resistant epilepsy. The etiologies of epilepsy for which hemispherectomy is performed are broadening, with no change in its safety profile. Seizure outcomes are better when the etiology of epilepsy is an ischemic injury, and the most common complication after the procedure is hydrocephalus. These findings reinforce the ongoing use of hemispherectomy as a safe and effective treatment option for certain individuals with drug-resistant epilepsy, support its application to a broader range of etiologies, and highlight areas of future investigation.

The Role of Physical Activity in Adjunctive Nursing Management of Neuro-Degenerative Diseases among Older Adults: A Systematic Review of Interventional Studies.

Neurodegenerative diseases such as dementia and Parkinson's disease pose significant challenges to older adults globally. While pharmacological treatments remain primary, increasing evidence supports the role of non-pharmacological strategies like physical activity in managing these conditions. This systematic review critically evaluates the effectiveness of Nursing based physical activity interventions in improving cognitive function, physical functioning, mobility, and overall quality of life among older adults with neurodegenerative diseases. We conducted a comprehensive search across PubMed, EMBASE, Web of Science, CENTRAL, and other relevant databases, focusing on randomized controlled trials and observational studies that examined the impact of structured physical activity. Our findings from nineteen studies involving 1673 participants indicate that interventions ranging from aerobic exercises, resistance training, to mind-body exercises like Tai Chi and yoga have beneficial effects. Specifically, physical activity was consistently found to enhance cognitive performance, increase mobility, and improve balance and daily living activities, contributing to a better quality of life. However, these benefits vary depending on the type, intensity, and duration of the activity performed. Despite promising results, limitations such as small sample sizes, study heterogeneity, and short-term follow-up periods call for more robust, long-term studies to solidify these findings. This review underscores the potential of tailored physical activity programs as adjunctive therapy in the comprehensive management of neurodegenerative diseases among the elderly population.

OUTCOMES OF ACUTE ANKLE DISTRACTION FOR INTRA-ARTICULAR DISTAL TIBIAL AND PILON FRACTURES

IntroductionIntra articular distal tibia fractures can lead to post-traumatic osteoarthritis. Joint distraction has shown promise in elective cases. However, its application in acute fractures remains unexplored. This pilot study aims to fill this knowledge gap by investigating the benefits of joint distraction in acute fractures.Materials & MethodsWe undertook a restrospective cohort study comprising patients with intra-articular distal tibia and pilon fractures treated with a circular ring fixator (CRF) at a single center. Prospective data collection included radiological assessments, Patient-Reported Outcome Measures (PROM), necessity for additional procedures, and Kellgren and Lawrence grade (KL) for osteoarthritis (OA).137 patients were included in the study, 30 in the distraction group and 107 in the non-distraction group. There was no significant difference between the groups.ResultsMean follow-up was 3.73 years. There was no significant difference between the groups in overall complications or need for further procedures. There was no significant difference in progression of KL between the groups (1.81 vs 2.0, p=0.38) mean follow up 1.90 years.PROM data was available for 44 patients (6 distraction, 38 non-distraction) with a mean follow-up of 1.71 years. There was no significant difference in EQ5D (p=0.32) and C Olerud-H Molander scores (p=0.17).ConclusionsThis pilot study suggests that joint distraction is safe in the acute setting. However, the study's impact is constrained by a relatively small patient cohort and a short-term follow-up period. Future investigations should prioritise longer-term follow-ups and involve a larger patient population to more comprehensively evaluate the potential benefits of joint distraction in acute fractures.

Nicaraven attenuates the acquired radioresistance of established tumors in mouse models via PARP inhibition.

Nicaraven has been reported to inhibit the activity of poly (ADP-ribose) polymerase (PARP). In this study, we investigated the probable ability of nicaraven to attenuate cancer radioresistance during fractionated radiotherapy. Tumor models were established in C57BL/6 mice and BALB/c nude mice by subcutaneous injection of Lewis mouse lung carcinoma cancer cells and A549 human lung cancer cells, respectively. When the tumors had grown to approximately 100 mm3, we initiated fractionated radiotherapy. Nicaraven or saline was administered immediately after each irradiation exposure. Compared to saline treatment, nicaraven administration significantly induced gamma-H2AX foci formation and cell apoptosis in tumors at 1 or 3days after an additional challenge exposure to 10Gy and inhibited tumor growth during the short-term follow-up period, suggesting increased radiosensitivity of cancer cells. Moreover, the expression of PARP in tumor tissue was decreased by nicaraven administration. Our data suggest that nicaraven likely attenuates the acquired radioresistance of cancers through PARP inhibition.

Effectiveness Evaluation of Low-dose Spiral Computed Tomography for Lung Cancer Screening in Minhang District of Shanghai

Low-dose spiral computed tomography (LDCT) has been recommended for lung cancer screening in high-risk populations. However, evidence from Chinese populations was limited due to the different criteria for high-risk populations and the short-term follow-up period. This study aimed to evaluate the effectiveness in Chinese adults based on the Lung Cancer Screening Program in Minhang District of Shanghai initiated in 2013. A total of 26,124 subjects aged 40 years or above were enrolled in the Lung Cancer Screening Program during the period of 2013 and 2017. Results of LDCT examination, and screen-detected cancer cases in all participants were obtained from the Reporting System of the Lung Cancer Screening Program. The newly-diagnosed cases and their vital status up to December 31, 2020 were identified through a record linkage with the Shanghai Cancer Registry and the Shanghai Vital Statistics. Standardized incidence ratio (SIR) and 95%CI were calculated using the local population at ages of 40 or above as the reference. Proportions of early-stage cancer (stage 0-I), pathological types, and 5-year observed survival rates of lung cancer cases were estimated and compared between the cases derived from the screened and non-screened populations. Cox regression models were applied to evaluate the hazard ratio (HR) and 95%CI of LDCT screening with all-cause death of the lung cancer cases. The crude and age-standardized incidence of lung cancer in screened population were 373.3 (95%CI: 343.1-406.1) and 70.3 per 100,000 person-years, respectively, with an SIR of 1.8 (95%CI: 1.6-1.9), which was observed to decrease with following-up time. The early-stage cancer accounted for 49.4% of all lung cancer cases derived from the screened population, significantly higher than 38.4% in cases from the non-screened population during the same period (P<0.05). The proportion of lung adenocarcinoma (40.7% vs 35.9%) and 5-year survival rate (53.7% vs 41.5%) were also significantly higher in the cases from the screened population (all P<0.05). LDCT screening was associated with 30% (HR=0.7, 95%CI: 0.6-0.8) reduced all-cause deaths of the cases. The participants of the screening program are at high-risk of lung cancer. LDCT favors the early-detection of lung cancer and improves 5-year survival of the screened cases, indicating a great potential of LDCT in reducing the disease burden of lung cancer in Chinese populations.

Effectiveness of online integrative trans-diagnostic treatment on internet addiction and high-risk behaviors in female adolescents with borderline personality disorder with comorbid depressive disorder.

Based on research, borderline personality disorder is associated with many behavioral and emotional problems, including Internet addiction and high-risk behaviors. On the other hand, integrative trans-diagnostic treatment, by targeting trans-diagnostic factors in emotional pathology, is considered a suitable treatment for comorbid psychological pathologies. Also, since in adolescence, the opinion of others about oneself is more important, online therapy has the advantage of protecting them from the fear of stigma and shame in the face of others' judgments. Therefore, the aim of the current research was to investigate the effectiveness of online integrative trans-diagnostic treatment on the internet addiction and high-risk behaviors in adolescents with borderline personality disorder. The current research was applied and quasi-experimental in a pre-test-post-test manner with a control group. The research sample included 40 female adolescents with borderline personality disorder who were randomly divided into two groups of 20 people, experimental and control groups. The criteria for entering the research included the age range of 12 to 18 years, female, confirmation of the disease by a psychologist, not receiving other psychological treatments in the last 3 months, and having a smartphone to participate in the online group. Substance abuse, any serious mental and physical illness/disorder that interferes with treatment, and failure to attend more than two sessions in therapy sessions were some of the exclusion criteria.The participants were tested on the scales of internet addiction and high-risk behaviors. Then, the treatment plan based on online integrative trans-diagnostic group therapy was presented to the participants of the experimental group online in 9 two-hour sessions. The control group was placed on the waiting list until the completion of the treatment sessions and the post-test implementation, and after the post-test implementation, they received the treatment. Then, their scores were measured, after completing the treatment, and a three-month follow-up period. Descriptive statistics and covariance test were used to analyze the data. Patients showed a clear improvement in the severity of internet addiction and high-risk behavior symptoms. So that the scores of internet addiction and high-risk behaviors in the experimental group after receiving the treatment, as well as after a three-month follow-up period, were significantly reduced (p < 0.001). These results show that online integrative trans-diagnostic therapy can be an effective treatment option for reducing some symptoms of risky behaviors and internet addiction in adolescents with borderline personality disorder and should be studied further. It is noteworthy that the limitations of this study were the available sampling method, the use of a unisex sample of female patients, and the short-term follow-up period, which makes it difficult to generalize the results.

Correlation between serum phosphate and all-cause mortality in critically ill patients with coronary heart disease accompanied by chronic kidney disease: a retrospective study using the MIMIC-IV database.

The adverse clinical endpoints of cardiovascular and kidney diseases are correlated with increased serum phosphate levels. However, in critically ill patients with coronary heart disease (CHD) accompanied by chronic kidney disease (CKD), the prognostic value of serum phosphate remains unclear. Patients' medical records from the Medical Information Mart for Intensive Care IV database who had concomitant CKD and CHD were classified into four distinct groups in this large retrospective observational cohort study based on the quartiles of serum phosphate levels. Vital status and the duration of hospital and ICU stays within the short-term follow-up periods of 30 and 90 days constituted the primary outcomes. All-cause mortality in the intensive care unit (ICU) and hospital constituted the secondary outcomes. Further, the Cox proportional hazard and restricted cubic spline (RCS) regression models were employed to ascertain how serum phosphate levels correlated with the primary outcomes. In addition, the occurrence rate of the secondary outcomes across the four quartiles was determined utilizing the Kaplan-Meier method. Among the total 3,557 patients (67.6% male) included, the hospital and ICU all-cause mortality rates were 14.6% and 10%, separately. Higher quartiles of serum phosphate concentrations were associated with shorter short-term survival rates, as shown by the Kaplan-Meier curves. Additionally, the Cox proportional hazards analysis illustrated that serum phosphate was independently linked to a higher death risk in the hospital [HR, 1.10 (95% CI: 1.03-1.18), P = 0.007] and ICU [HR, 1.14 (95% CI: 1.07-1.22), P < 0.001]. Lastly, the RCS regression models suggested a robust non-linear correlation between serum phosphate concentrations and death risk in the ICU and hospital (both P for non-linearity <0.001). The prognostic value of serum phosphate is significant in critically ill patients with CHD accompanied by CKD. Furthermore, serum phosphate is potentially valuable for identifying patients with this concomitant condition.

Clinical Manifestations and Adverse Cardiovascular Events in Patients with Cardiovascular Symptoms after mRNA Coronavirus Disease 2019 Vaccines.

The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

Emapalumab, a Fully Human Anti-Interferon Gamma Monoclonal Antibody, in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis: Long-Term Follow-up of a Phase 2/3 Study

Background: Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare, life-threatening genetically heterogeneous, autosomal recessive disorder, characterized by immune dysregulation and hyperinflammation. Acute treatment of pHLH has traditionally involved immunochemotherapy with glucocorticoids and etoposide to suppress hyperinflammation and facilitate the patient undergoing allogeneic hematopoietic stem cell transplantation (HSCT), the only potentially curative therapy. Emapalumab, a fully human immunoglobulin G1 anti-interferon-γ (IFNγ) monoclonal antibody, binds free and receptor-bound IFNγ, neutralizing its biologic activity. Emapalumab has demonstrated efficacy in patients with pHLH and has a favorable safety profile with no increase in the risk of adverse events (AEs), including infections, with increasing drug exposure prior to patients undergoing HSCT. Objective: To monitor the long-term safety and efficacy of emapalumab in patients with pHLH, including the period after undergoing HSCT. Methods: Long-term follow-up study (NCT02069899) of patients with pHLH who had received ≥1 dose of emapalumab in a multicenter, single-arm, open-label phase 2/3 clinical trial who were followed for 1 year after HSCT or last administration of emapalumab in the parent study (NCT01818492). Patients received emapalumab for 4 to 8 weeks in the parent study, which included a 4-week short-term follow-up period, during which patients could have undergone HSCT. Treatment with emapalumab could continue according to the parent study protocol during follow-up, if a favorable benefit/risk assessment was established. Any concomitant treatment ongoing at the time of study entry was continued as considered necessary by the investigators. Endpoints included safety, 1-year survival, and HSCT outcomes. Results: Overall, 37/45 patients who participated in the phase 2/3 study entered long-term follow-up, with 24 patients (64.9%) completing the study; 13 patients (35.1%) withdrew from the study, most commonly because of AEs (6 patients [46.2%]) and withdrawal of informed consent (2 patients [15.4%]). All patients had ≥1 concomitant medications including systemic corticosteroids and ≥1 systemic antimicrobial. Emapalumab treatment continued during long-term follow-up for 22 patients (59.5%). All patients experienced at least one AE during follow-up ( Table), most commonly infections or infestations (27 patients [73.0%] reported an infection AE). Most AEs were mild or moderate in intensity. Four patients (10.8%) had study drug-related AEs. Overall, 56.8% of patients experienced at least one severe AE. 28 patients (75.7%) experienced at least 1 serious AE (SAE), but only 1 patient (2.7%) had a treatment-related SAE (Coombs positive hemolytic anemia). Infusion-related reactions of rash were observed in 2 patients (5.4%), but these reactions were temporary and resolved without treatment. No patients experienced AEs leading to study drug discontinuation. Nine patients died during the study (4 prior to HSCT conditioning and 5 during the post-conditioning period). No study drug-related deaths were reported. 28 (75.7%) patients were alive at last observation or 1 year after last emapalumab dose and 33 (89.2%) survived to undergo HSCT or until 1 year after last emapalumab dose (whichever came first). 29 patients (78.4%) underwent HSCT, including 18 during long-term follow-up. 24 of the 29 (82.8%) patients who underwent HSCT were alive at last observation or 1 year after last emapalumab dose. Sustained engraftment was achieved in 23 patients (79.3%; 95% confidence interval, 61.6-90.2%). During the follow-up period, 6 patients (20.7%; 95% confidence interval [CI], 9.8-38.4%) experienced primary or secondary graft failure after undergoing HSCT and 7 patients (24.1%; 95% CI, 1.2-42.1%) had acute or chronic graft-versus-host disease. At the 12-months post-transplant visit, 25/26 (96.2%) patients maintained a complete response, while 1 (3.8%) patient was reported to have maintained a partial response. No pHLH reactivation was reported during the study. Conclusions: The long-term outcomes for patients with pHLH treated with emapalumab are consistent with observations made during a phase 2/3 study. A favorable safety profile was maintained, and a high proportion of patients received HSCT and achieved long-term survival.