Clinical Variables Research Articles

Patient-reported, clinical and radiological factors associated with the result after non-surgical management of acute AC joint dislocation Rockwood type III and V.

The treatment of Rockwood type III and V acromioclavicular (AC) joint dislocations is controversial, and an individualized treatment algorithm is yet to be developed. The objective of this study was to investigate the association of demographical, clinical, patient-reported and radiological variables with the Western Ontario Shoulder Instability Index (WOSI) score and risk of surgery. Inclusion criteria for this prospective cohort study were patients aged 18-60 with an acute AC joint dislocation with >25% increase in the coracoclavicular distance on bilateral Zanca radiographs. Patients were treated non-surgically with 3 months of home-based training and the option of delayed surgical intervention. The outcomes were the WOSI score and surgery yes/no. Demographical, clinical, patient-reported (WOSI and Shoulder Pain and Disability Index [SPADI]) and radiological variables were collected at baseline and 6 weeks after the injury and investigated for association with the outcomes at 3 months, 6 months and 1 year. Ninety-five patients with Rockwood type III/V AC joint dislocation were included. Pre-injury participation in overhead/collision sports was a risk factor for surgery with an odds ratio of 5 (p = 0.03). Reduced range of motion (ROM) at baseline was associated with reduced WOSI scores and increased risk of surgery. At 6 weeks, reduced ROM, increased SPADI and increased pain during cross-over were associated with the outcomes. Radiological measurements were not correlated with the result. At the 6 weeks follow-up, patients eventually requiring surgery could be detected with a sensitivity of 100% and a specificity of 94% based on a SPADI score of >30 and a ROM ≤ 140° in shoulder flexion or abduction. ROM was the only variable consistently associated with both WOSI and risk of surgery. Six weeks after the injury, it was possible to detect patients in need of surgery based on ROM and SPADI with a sensitivity of 100% and a specificity of 94%. Level II.

Rituximab retention rate in systemic sclerosis: a long term real-life multicenter study.

to report real-life data on rituximab retention-rate as indicator of safety and efficacy in a multicentric national cohort of systemic sclerosis patients. SSc patients treated with rituximab and followed for at least 36 months were included, clinically characterized, and longitudinally monitored. A competing risk analysis with sub-Hazard Ratio(sHR) definition was performed to explore the clinical variables linked to specific cause of rituximab discontinuation. One-hundred-fifty-two SSc-patients (mean age 47.3 ± 12.3 years; females 79.6%; diffuse disease 77.6%; anti-topoisomerase-I positivity 63.2%) were evaluated over a median(IQR) time of 3.3(1.7-5.0) years. The primary indication for rituximab were interstitial lung disease (ILD)(38.8%), worsening skin fibrosis(36.8%), and arthritis(13.8%); 138 patients(90.8%) received more than one rituximab course. The 5-years rituximab retention rate was 59.9%(44.6-64.7%). Clinical response was the most common reason for rituximab discontinuation[5.7(3.7-8.4) per 100 patient-year] and was associated with a shorter disease duration[sHR 0.8(0.7-0.9)], anti-topoisomerase-I negativity[sHR 0.4(0.2-0.9)], previous digital ulcers[sHR 2.6(1.1-6.2] and no history of arthritis[sHR 0.3 (0.1-0.8)]. Treatment failure was the second cause of rituximab discontinuation[3.7(2.2-6.0) per 100 patient-year] and was associated with anti-centromere antibody positivity[sHR 2.8(1.1-7.4)] and anti-topoisomerase-I negativity[sHR 0.2(0.1-0.6)]. Adverse events(AEs) were the less common cause of discontinuation[3.1(1.7-5.2) per 100 patient-year], associated with limited cutaneous subset[sHR 3.4(1.2-9.7)] and previous mycophenolate mofetil treatment[sHR 4.5(1.2-16.3)]. rituximab is a safe and effective treatment in SSc: clinical response emerged as the primary reason for rituximab discontinuation, and AEs had a limited impact on treatment persistence. The identification of specific disease features associated with a response to rituximab will be useful in the management of SSc-patients.

Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-Institutional Prospective Cohort Evaluation.

Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathological factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer(BC) chemotherapy response remains poorly understood. This study examines the variance in the gut microbiome(GM) of BC patients compared to healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease. Our study reveals distinct clustering, effectively separating the BC and healthy cohorts. However, no significant differences were observed between chemotherapy responders and non-responders within community subgroups. Machine Learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs AUC 0.50), although no single microbial species emerged as a fully reliable biomarker. The evaluation of short-chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, p = 0.017) and Clostridia (rs = 0.52, p = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, p=0.02) and Enterobacteriaceae (rs = 0.52, p < 0.03) correlated with increased fecal propionic acid. In conclusion, our study constitutes the first large-scale, multi-center assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa.

Deep Learning for Predicting Progression of Patellofemoral Osteoarthritis Based on Lateral Knee Radiographs, Demographic Data, and Symptomatic Assessments.

In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of 7 years. This study included subjects (1,832 subjects, 3,276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a five-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, body mass index, and Western Ontario and McMaster Universities Arthritis Index score, and the radiographic osteoarthritis stage of the tibiofemoral joint (Kellgren and Lawrence [KL] score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data. Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an area under the receiver operating characteristic curve (AUC) of 0.856 and average precision (AP) of 0.431, slightly outperforming the deep learning approach without attention (AUC = 0.832, AP = 0.4) and the best performing reference GBM model (AUC = 0.767, AP = 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP = 0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur. This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

24-h energy expenditure in people with type 1 diabetes: impact on equations for clinical estimation of energy expenditure.

Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.

Prevalence and Outcomes of Gastrointestinal Anomalies in Down Syndrome.

Our objective was to investigate the prevalence of small intestinal atresia and Hirschsprung's disease (HD) in infants with Down syndrome (DS) and its impact on outcomes. We analyzed the National Inpatient Sample dataset. We included infants with DS, small intestinal atresia, HD, and the concomitant occurrence of both conditions. Regression analysis was used to control clinical and demographic variables. A total of 66,213,034 infants were included, of whom, 99,861 (0.15%) had DS. The concomitant occurrence of small intestinal atresia and HD was more frequent in infants with DS compared with the general population, adjusted odds ratio (aOR): 122, 95% confidence interval (CI): 96-154, (p < 0.001). Infants with DS and concomitant small intestinal atresia and HD had higher mortality compared with those without these conditions, aOR: 8.59, 95% CI: 1.95-37.8. Infants with DS are at increased risk of concomitant small intestinal atresia and HD, and this condition is associated with increased mortality. · Infants with Down syndrome are at increased risk of congenital GI anomalies.. · Infants with Down syndrome are at increased risk of necrotizing enterocolitis.. · Increased mortality in Down syndrome infants with concomitant small intestinal atresia and Hirschsprung's disease..

Skull Density Ratio as Arm-Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson's Disease.

MR-guided focused ultrasound (FUS) thermoablation is an established therapy for movement disorders. FUS candidates must meet a predefined threshold of skull density ratio (SDR), a parameter that accounts for the efficiency in reaching ablative temperatures. Randomized sham-controlled trials to provide definitive therapeutic evidence employ pure randomization of subjects into active treatment or control arms. The latter design has several general limitations. To demonstrate that SDR values are not associated with clinically and demographically relevant variables in patients with Parkinson's disease (PD). This in turn would allow using SDR as an arm-allocation parameter, separating patients who will receive active FUS treatment and best medical management treatment (BMT). We studied a cohort of 215 PD patients who were candidates for FUS subthalamotomy to determine if the SDR was correlated with demographic or clinical variables that could introduce bias for group allocation in a controlled trial. SDR was unassociated with age, gender, and clinical motor features nor with levodopa daily dose in our cohort of PD patients. A negative association with age was found for the female subgroup. Our results show that in a PD population considered for FUS subthalamotomy treatment, the SDR may be a valid group-allocation parameter. This could be considered as the basis for a controlled study comparing FUS subthalamotomy vs BMT.

CatLet score and clinical CatLet score as predictors of long-term outcomes in patients with acute myocardial infarction presenting later than 12 hours from symptom onset

Background Our recently developed C oronary A rtery T ree description and L esion E valua T ion (CatLet) angiographic scoring system is unique in its description of the variability in the coronary anatomy, the degree of stenosis of a diseased coronary artery, and its subtended myocardial territory, and can be utilized to predict clinical outcomes for patients with acute myocardial infarction (AMI) presenting ≤12 h after symptom onset. The current study aimed to assess whether the Clinical CatLet score (CCS), as compared with CatLet score (CS), better predicted clinical outcomes for AMI patients presenting >12 h after symptom onset. Methods CS was calculated in 1018 consecutive AMI patients enrolled in a retrospective registry. CCS was calculated by multiplying CS by the ACEF I score (age, creatinine, and left ventricular ejection fraction). Primary endpoint was major adverse cardiac events (MACEs) at 4-year-follow-up, a composite of cardiac death, myocardial infarction, and ischemia-driven revascularization. Results Over a 4-year follow-up period, both scores were independent predictors of clinical outcomes after adjustment for a broad spectrum of risk factors. Areas-under-the-curve (AUCs) for CS and CCS were 0.72(0.68–0.75) and 0.75(0.71–0.78) for MACEs; 0.68(0.63–0.73) and 0.78(0.74–0.83) for all-cause death; 0.73(0.68–0.79) and 0.83(0.79–0.88) for cardiac death; and 0.69(0.64–0.73) and 0.75(0.7–0.79) for myocardial infarction; and 0.66(0.61–0.7) and 0.63(0.58–0.68) for revascularization, respectively. CCS performed better than CS in terms of the above-mentioned outcome predictions, as confirmed by the net reclassification and integrated discrimination indices. Conclusions CCS was better than CS to be able to risk-stratify long-term outcomes in AMI patients presenting >12 h after symptom onset. These findings have indicated that both anatomic and clinical variables should be considered in decision-making on management of patients with AMI presenting later.

Exploring the mystery of colon cancer from the perspective of molecular subtypes and treatment

The molecular categorization of colon cancer patients remains elusive. Gene set enrichment analysis (GSEA), which investigates the dysregulated genes among tumor and normal samples, has revealed the pivotal role of epithelial-to-mesenchymal transition (EMT) in colon cancer pathogenesis. In this study, we employed multi-clustering method for grouping data, resulting in the identification of two clusters characterized by varying prognostic outcomes. These two subgroups not only displayed disparities in overall survival (OS) but also manifested variations in clinical variables, genetic mutation, and gene expression profiles. Using the nearest template prediction (NTP) method, we were able to replicate the molecular classification effectively within the original dataset and validated it across multiple independent datasets, underscoring its robust repeatability. Furthermore, we constructed two prognostic signatures tailored to each of these subgroups. Our molecular classification, centered on EMT, hold promise in offering fresh insights into the therapy strategies and prognosis assessment for colon cancer.

Effect of drug therapies on self‐reported chemosensory outcomes after COVID‐19

AbstractObjectiveThe aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection on self‐reported alterations in taste and/or smell function.MethodsSeven hundred and fourteen persons with self‐reported postcoronavirus disease 2019 (post‐COVID‐19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure—self‐reported total recovery of chemosensory symptoms—was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc).ResultsThe median time between COVID‐19 symptom onset and the interviews was 81 days (interquartile range: 60–104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self‐reported taste or smell recovery. Those who took oral zinc were less likely to improve.ConclusionsNo medication employed during the first months after SARS‐CoV‐2 infection had a clear positive effect on returning self‐reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

Location-based clinical and angiographic profile of brain arteriovenous malformations - a single-center observational study.

The location of brain arteriovenous malformations (bAVM) is one of the most relevant prognostic factors included in surgical, endovascular and radiosurgical scores. However, their characteristics according to location are seldom described. The goal of this study was to describe the clinical and angiographic characteristics of bAVM classified according to their location. This retrospective observational study included patients diagnosed with bAVM and attending a national referral hospital during the period 2010-2020. Data regarding clinical and angiographic variables were extracted, including characteristics on nidus, arterial afferents, venous drainage and associated aneurysms. BAVM were classified in 8 groups according to their location: frontal, temporal, parieto-occipital, periventricular, deep, cerebellar, brainstem and mixed. Data distribution for each group was determined and between-group differences were assessed. A total of 269 bAVM (in 258 patients) were included. The most frequent location was parieto-occipital; and the least frequent, brainstem. Statistically significant differences were observed between groups for most studied variables, including: clinical presentation, functional status at admission; nidus size and density, classification according to the Spetzler-Martin, Buffalo and modified Pollock-Flickinger scales; number, diameter, origin and type of afferents; number, diameter, type and direction of venous drainage, retrograde venous flow; and presence and size of flow-related aneurysms. The clinical and angiographic differences observed between brain AVM groups allow the formulation of profiles according to their location.

Hospital Readmissions in Patients Supported with Durable Centrifugal-Flow Left Ventricular Assist Devices

Background: Centrifugal-flow left ventricular assist devices (CF-LVADs) have improved morbidity and mortality for their recipients. Hospital readmissions remain common, negatively impacting quality of life and survival. We sought to identify risk factors associated with hospital readmissions among patients with CF-LVADs. Methods: Consecutive patients receiving a CF-LVAD between February 2011 and March 2021 were retrospectively evaluated using prospectively maintained institutional databases. Hospital readmissions within three years post-LVAD implantation were dichotomized into heart failure (HF)/LVAD-related or non-HF/LVAD-related readmissions. Multivariable Cox regression models augmented using a machine learning algorithm, the least absolute shrinkage and selection operator (LASSO) method, for variable selection were used to estimate associations between HF/LVAD-related readmissions and pre-, intra- and post-operative clinical variables. Results: A total of 204 CF-LVAD recipients were included, of which 138 (67.7%) had at least one HF/LVAD-related readmission. HF/LVAD-related readmissions accounted for 74.4% (436/586) of total readmissions. The main reasons for HF/LVAD-related readmissions were major bleeding, major infection, HF exacerbation, and neurological dysfunction. Using pre-LVAD variables, HF/LVAD-related readmissions were associated with substance use, previous cardiac surgery, HF duration, pre-LVAD inotrope dependence, percutaneous LVAD/VA-ECMO support, LVAD type, and the left ventricular ejection fraction in multivariable analysis (Harrell’s concordance c-statistic; 0.629). After adding intra- and post-operative variables in the multivariable model, LVAD implant hospitalization length of stay was an additional predictor of readmission. Conclusions: Using machine learning-based techniques, we generated models identifying pre-, intra-, and post-operative variables associated with a higher likelihood of rehospitalizations among patients on CF-LVAD support. These models could provide guidance in identifying patients with increased readmission risk for whom clinical strategies to mitigate this risk may further improve LVAD recipient outcomes.

End of Life Outcomes Following Comfort Care Orders: A Single Center Experience.

Background: Few studies have explored the outcomes of patients placed on comfort care with respect to hospice disposition. The objective of this study was to perform a retrospective analysis of patients who transitioned to comfort care. Methods: We conducted a retrospective study of patients placed on the comfort care order set between July 1st, 2021, until June 30th, 2022. Each individual patient chart was then analyzed to collect multiple clinical variables. IRB approval was obtained as per institutional guidelines. Results: 541 patients were included in the analysis. An average of 1.5 patients were placed on comfort care a day. 424 (78.37%) patients died while in the hospital. The median time on comfort care was 1 day. For subspecialty and hospital medicine patients the median time was 2 days. 40% of non-ICU patients were discharged with hospice services. 60% of patients were in the intensive care unit (ICU) and spent a median of 2.33 hours on comfort care. 19% of these patients were on comfort care for over 12 hours. 94% of the patients placed on comfort care in the ICU died in the hospital as compared to 53% of subspecialty and 59% of hospital medicine patients. Conclusions: The majority of patients placed on comfort care died during their hospitalization demonstrating a real need for comprehensive end of life care and immediate hospice services. For those discharged with hospice services, they spent an excessive amount of time in the hospital waiting for services to be arranged.

Active but not quiescent lupus nephritis during pregnancy is associated with a higher rate of adverse obstetric outcomes: Analysis of a prospective cohort.

To compare the maternal-fetal/neonatal outcome in patients with systemic lupus erythematosus (SLE) with and without lupus nephritis (LN) in remission or with active disease. A prospective cohort of pregnant patients with SLE (ACR 1997 criteria) was studied from January 2009 to December 2021. Demographic, clinical, biochemical, and immunological variables as well as the usual maternal-fetal/neonatal complications were recorded. We compared four groups according to the status of SLE during pregnancy: patients with quiescent SLE without lupus nephritis, patients with active SLE without lupus nephritis, patients with quiescent lupus nephritis, and patients with active lupus nephritis. Statistical analysis included descriptive statistics, bivariate analysis, and Cox regression analysis. A total of 439 pregnancies were studied, with a median age of 28 ± 6, SLE duration of 60 months (interquartile range 36-120). A higher frequency of maternal and fetal/neonatal complications was observed in patients with active SLE with or without lupus nephritis. Multivariate analysis showed that active LN was a risk factor for gestational hypertension (hazard ratios [HR] 1.95; 95% confidence intervals [CI]: 1.01-6.39), premature rupture of membranes (HR 3.56; 95% CI: 1.79-16.05) and more frequent cesarean section (HR 1.82; 95% CI: 1.13-2.94). LN is associated with a higher frequency of maternal complications, especially in those patients with active disease during pregnancy, and those maternal complications had an impact on poor fetal/neonatal outcomes. Strict control and timely care of LN could improve the obstetric prognosis.

Prognostic significance and immune landscape of a cell cycle progression-related risk model in bladder cancer

BackgroundA greater emphasis has been placed on the part of cell cycle progression (CCP) in cancer in recent years. Nevertheless, the precise connection between CCP-related genes and bladder cancer (BCa) has remained elusive. This study endeavors to establish and validate a reliable risk model incorporating CCP-related factors, aiming to predict both the prognosis and immune landscape of BCa.MethodsClinical information and RNA sequencing data were collected from the GEO and TCGA databases. Univariate and multivariate Cox regression analyses were conducted to construct a risk model associated with CCP. The performance of the model was assessed using ROC and Kaplan–Meier survival analyses. Functional enrichment analysis was employed to investigate potential cellular functions and signaling pathways. The immune landscape was characterized using CIBERSORT algorithms. Integration of the risk model with various clinical variables led to the development of a nomogram.ResultsTo build the risk model, three CCP-related genes (RAD54B, KPNA2, and TPM1) were carefully chosen. ROC and Kaplan–Meier survival analysis confirm that our model has good performance. About immunological infiltration, the high-risk group showed decreased levels of regulatory T cells and dendritic cells coupled with increased levels of activated CD4 + memory T cells, M2 macrophages, and neutrophils. Furthermore, the nomogram showed impressive predictive power for OS at 1, 3, and 5 years.ConclusionThis study provides new insights into the association between the CCP-related risk model and the prognosis of BCa, as well as its impact on the immune landscape.

The learning curve for minimally invasive Achilles repair using the “lumbar puncture needle and oval forceps” technique

IntroductionAn acute Achilles tendon rupture represents a common tendon injury, and its operative methods have been developed over the years. This study aimed to quantify the learning curve for the minimally invasive acute Achilles tendon rupture repair.MethodsFrom May 2020 to June 2022, sixty-seven patient cases who received minimally invasive tendon repair were reviewed. Baseline data and operative details were collected. The cumulative summation (CUSUM) control chart was used for the learning curve analyses. Achilles tendon rupture score (ATRS), American Orthopedic Foot and Ankle Society (AOFAS) ankle/hindfoot score, and visual analog scale (VAS) at 3/6/9/12 months were calculated to assess the clinical outcomes.ResultsThirty-six cases underwent at least a year of follow up and were enrolled in this study. The gender ratio and average age were 80.5% and 32.5 years. The linear equation fitted well (R2 = 0.95), and CUSUM for operative time peaked in the 12th case, which was divided into the learning phase (n = 12) and master phase (n = 24). No significant difference was detected between the two groups in clinical variables, except for the operative time (71.1 ± 13.2 min vs 45.8 ± 7.2 min, p = 0.004). Moreover, we detected one case with a suture reaction and treated it properly.ConclusionMinimally invasive Achilles repair provides an opportunity for early rehabilitation. Notably, the learning curve showed that the “lumbar puncture needle and oval forceps” technique was accessible to surgeons.

Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study

Background & aimsComplications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases.MethodsPatients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications.ResultsSixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7–51.8) in the control group and 8.7 (range 8.7–43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis.ConclusionThe 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Ozone therapy by rectal insufflation in dogs: safety and oxidative stress - a randomized cross-over study.

Ozone therapy acts in the body inducing controlled oxidative stress, thereby improving the antioxidant, immune and circulatory responses. However, very little is known about how this therapy affects oxidative stress indicators in dogs. We aimed to assess the clinical, hematological, biochemical and oxidative stress parameters of healthy dogs subjected to ozone therapy and oxygen therapy by rectal insufflation. Ten healthy dogs were allocated into three experimental groups in a cross-over design: control, without intervention; ozone, which received 100µg of O3/kg through rectal insufflation; and oxygen, which received an ozone-equivalent volume of medicinal O2 through rectal insufflation. Dogs received four applications weekly and were followed up until the seventh week. Ozone therapy significantly increased the weight, mean corpuscular volume and mean platelet volume and decreased total cholesterol of treated dogs. Regarding oxidative stress, ozone therapy reduced total antioxidant capacity by ferric reduction (TAC-FRAP) in D7 compared with baseline and the control, significantly increased total antioxidant capacity by cupric reduction (TAC-CUPRAC) in D42 and D49 compared with the control group, caused an increase in uric acid compared with the oxygen group and decreased lipid peroxidation on D21 compared with the control group. In conclusion, ozone therapy through rectal insufflation causes transient oxidative stress followed by an antioxidant response and discreetly interferes with a few clinical, hematological and biochemical variables in healthy dogs, although variables still remained within the reference ranges for the species, thus proving the safety of the therapy. Furthermore, oxygen therapy causes oxidative stress without inducing a subsequent antioxidant response.

Mitochondrial DNA in bronchoalveolar lavage fluid is associated with the prognosis of idiopathic pulmonary fibrosis: a single cohort study

BackgroundExtracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF.MethodsExtracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed.ResultsmtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p < 0.001) and ≥ 11,194.3 copies/µL at the time of AE (MST: 2.6 vs. 20.0 months, p = 0.03) were associated with shorter survival after BALF collection, even after adjusting for other known prognostic factors. On the other hand, BALF-nucDNA showed different trends in correlation with other clinical variables and did not show any significant association with survival time.ConclusionsElevated BALF-mtDNA was associated with a poor prognosis in both IPF and AE-IPF. Of note, at the time of AE, it sharply distinguished survivors from non-survivors. Given the trends shown by analyses for BALF-nucDNA, the elevation of BALF-mtDNA might not simply reflect the impact of cell collapse. Further studies are required to explore the underlying mechanisms and clinical applications of BALF-mtDNA in IPF.

Meningioma recurrence: Time for an online prediction tool?

Background: Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient’s lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson’s and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care. Methods: A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population. Results: Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, CDKN2A deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas. Conclusion: Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas.