Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation.

OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN: Multi-institutional historical cohort study. SETTING: Five tertiary care referral centers. PATIENTS: Adults ≥18 years old with sporadic VS. INTERVENTION: Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS. RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

The value of G-CSF in women experienced at least one implantation failure: a systematic review and meta-analysis.

Objective: Despite the developments of in vitro fertilization (IVF) protocols, implantation failure remains a challenging problem, owing to the unbalance between the embryo, endometrium, and immune system interactions. Effective treatments are urgently required to improve successful implantation. Recently, many researchers have focused on granulocyte colony-stimulating factor (G-CSF) to regulate immune response and embryo-endometrium cross-talk. However, previous studies have reported inconsistent findings on the efficacy of G-CSF therapy on implantation failure. The objective of this review was to further explore the effects of G-CSF according to administration dosage and timing among women who experienced at least one implantation failure. Methods: We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials of G-CSF on implantation failure up to July 21, 2023. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and the heterogeneity of the studies with the I2 index was analyzed. Results: We identified a total of 2031 studies and finally included 10 studies in the systematic review and meta-analysis. G-CSF administration improved the clinical pregnancy rate (CPR), implantation rate (IR), biochemical pregnancy rate (BPR), and live birth rate (LBR) in women with at least one implantation failure. Subgroup analyses showed that G-CSF treatment could exert good advantages in improving CPR [OR=2.49, 95%CI (1.56, 3.98), I2 = 0%], IR [OR=2.82, 95%CI (1.29, 6.15)], BPR [OR=3.30, 95%CI (1.42, 7.67)] and LBR [OR=3.16, 95%CI (1.61, 6.22), I2 = 0%] compared with the blank control group. However, compared with placebo controls, G-CSF showed beneficial effects on CPR [OR=1.71, 95%CI (1.04, 2.84), I2 = 38%] and IR [OR=2.01, 95%CI (1.29, 3.15), I2 = 24%], but not on LBR. In addition, >150µg of G-CSF treatment increased CPR [OR=2.22, 95%CI (1.47, 3.35), I2 = 0%], IR [OR=2.67, 95%CI (1.47, 4.82), I2 = 0%] and BPR [OR=2.02, 95%CI (1.17, 3.47), I2 = 22%], while ≤150µg of G-CSF treatment improved miscarriage rate (MR) [OR=0.14, 95%CI (0.05, 0.38), I2 = 0%] and LBR [OR=2.65, 95%CI (1.56, 4.51), I2 = 0%]. Moreover, G-CSF administration on the day of embryo transfer (ET) could increase CPR [OR=2.81, 95%CI (1.37, 5.75), I2 = 0%], but not on the day of ovum pick-up (OPU) or human chorionic gonadotropin (HCG) injection. Conclusion: G-CSF has a beneficial effect on pregnancy outcomes to some extent among women who experienced at least one implantation failure, and the administration dosage and timing influence the effect size.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023447046.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

PaCO2 is nonlinearly associated with NIV failure in patients with hypoxemic respiratory failure.

OBJECTIVE: To explore the association between PaCO2 and noninvasive ventilation (NIV) failure in patients with hypoxemic respiratory failure. METHODS: A retrospective study was performed in a respiratory ICU of a teaching hospital. Patients admitted to ICU between 2011 and 2019 were screened. We enrolled the patients with hypoxemic respiratory failure. However, patients who used NIV due to acute-on-chronic respiratory failure or heart failure were excluded. Data before the use of NIV were collected. Requirement of intubation was defined as NIV failure. RESULTS: A total of 1029 patients were enrolled in final analysis. The rate of NIV failure was 45% (461/1029). A nonlinear relationship between PaCO2 and NIV failure was found by restricted cubic splines (p = 0.03). The inflection point was 32 mmHg. The rate of NIV failure was 42% (224/535) in patients with PaCO2 >32 mmHg. However, it increased to 48% (237/494) in those with PaCO2 ≤ 32 mmHg. The crude and adjusted hazard ratio (HR) for NIV failure was 1.36 (95%CI:1.13-1.64) and 1.23(1.01-1.49), respectively, if the patients with PaCO2 >32 mmHg were set as reference. In patients with PaCO2 ≤ 32 mmHg, one unit increment of PaCO2 was associated with 5% reduction of NIV failure. However, it did not associate with NIV failure in patients with PaCO2 >32 mmHg. CONCLUSIONS: PaCO2 and NIV failure was nonlinear relationship. The inflection point was 32 mmHg. Below the inflection point, lower PaCO2 was associated with higher NIV failure. However, it did not associate with NIV failure above this point.

Determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in Tigray Region, Ethiopia: a case-control study.

BACKGROUND: Multidrug-resistant tuberculosis is a type of tuberculosis that is resistant to at least the first-line antituberculosis drugs namely, rifampicin and isoniazid. However, most of these studies were limited only to a single hospital. Therefore, this study aimed to identify the determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in the Tigray region of Ethiopia. METHODS: Hospital-based unmatched case-control study was conducted from 1 April 2019 to 30 June 2019. A simple random sampling method was used to select the required sample size. Variables at a p value less than 0.25 in bivariate analysis were entered into a multivariable analysis to identify the determinant factors of multidrug-resistant tuberculosis. Finally, the level of significance was declared at p<0.05. RESULTS: Rural residence (adjusted OR (AOR) 2.54; 95% CI 1.34 to 4.83), HIV (AOR 4.5; 95% CI 1.4 to 14.2), relapse (AOR 3.86; 95% CI 1.98 to 7.5), return after lost follow-up (AOR 6.29; 95% CI 1.64 to 24.2), treatment failure (AOR 5.87; 95% CI 1.39 to 24.8) were among the determinants of multidrug-resistant tuberculosis. CONCLUSION: Rural residence, HIV, relapses, return after lost follow-up and treatment failure were the identified determinant factors of multidrug-resistance tuberculosis.

Managing failed vital pulp therapies in mature permanent teeth in a retrospective cohort study, with success and survival rates of managing protocols.

Despite advancements in vital pulp therapy (VPT), a subset of cases fails to achieve desired outcomes. This study based on a previous large-scale cohort study involving 1257 VPT-treated teeth, aiming to describe the demographic data and clinical characteristics of all failed cases and their management protocols. Clinical records/images of 105 failed cases treated by a single endodontist (2011-2022) were examined, including 10 extracted teeth. Asymptomatic cases with PDL widening received no intervention, while others underwent management protocols, including (selective) RCT and (tampon) re-VPT. These retreatments were assessed for success (defined as radiographic evidence of healing) and survival (characterized by the retention/function of the treated tooth) using Kaplan-Meier analysis. While 51.4% of all initial failures were diagnosed due to symptoms, 48.6% were symptom-free. Notably, failed cases with symptomatic irreversible pulpitis, and apical periodontitis/widened PDL before initial treatment significantly outnumbered asymptomatic cases and normal PDL, respectively (P = 0.001). Moreover, most of the initial failures were observed in teeth with composite resin rather than amalgam restorations (P = 0.002). The success and survival rates for the management protocols were 91.78% and 95.79%, respectively, over an average follow-up period of 36.94 (± 23.30) months. RCT and re-VPT procedures provide successful outcomes for managing unsuccessful VPTs.

Basicervical femoral neck fractures: an observational study derived from the Swedish Fracture Register.

BACKGROUND AND PURPOSE: Limited research has been conducted on basicervical femoral neck fractures (bFNFs). The importance of displacement in clinical outcomes remains unclear. We aimed to characterize patient demographics, degree of displacement, treatment, treatment failures, and reoperations in a cohort of fractures from the Swedish Fracture Register (SFR). METHODS: 1,260 fractures in 1,185 individuals ≥ 60 years who had a bFNF registered in the SFR at 6 orthopedic departments from 2011 to 2020 were screened through radiographic review. The final sample included 291 patients with a confirmed bFNF. The medical records of these 291 patients were reviewed. We assessed baseline characteristics, initial fracture dislocation, treatment methods, tip-apex distance, failures, reoperations, and mortality. RESULTS: The mean age was 82 years (range 60-101, 55% women). 98 (34%) were undisplaced and 193 (66%) displaced. All patients underwent operative treatment. In the undisplaced group 95 (97%) patients received internal fixation (IF) and 3 (3%) had primary hip arthroplasty. In the displaced group 149 (77%) received IF and 41 (21%) had primary hip arthroplasty. 33 (11%) suffered treatment failure. When treating an undisplaced bFNF with IF, only 3 (3%) experienced treatment failure, in contrast to the 24 (16%) failure rate for a displaced bFNF. CONCLUSION: Undisplaced bFNFs have a low failure rate when treated with IF. For displaced bFNF treated with IF the failure rate is considerably higher. There is a need for further investigation of classification, treatment, and outcome of bFNF.

Management of anal fistulas in Crohn's disease after failure of Infliximab.

INTRODUCTION: Treatment of complex perianal fistulas in Crohn's disease remains a challenge especially after the failure of Infliximab. AIM: Update on the different therapeutic alternatives for anal fistula in Crohn's disease after failure of Infliximab. METHODS: A research in the medical literature on PubMed and Google Scholar was carried out. We included cohort studies, reviews and randomized double-blinded therapeutic trials. Case reports and fundamental research studies have been excluded. RESULTS: Anti-TNF therapy, notably Infliximab remain the therapeutic option of choice. Since Infliximab efficacy has been estimated at 60%, with a significant loss-of response rate, new therapeutic strategies have been evaluated and may offer new opportunities for the management of anal fistulas: for example, Ustekinumab could be effective after failure of anti-TNF therapy, although further studies are required. Recent guidelines suggest that injection of mesenchymal stem cells is an effective and safe treatment for complex fistulas. Other surgical options have been proposed, such as endorectal advancement flap, fibrin glue injection, anal fistula plug and ligation of the intersphincteric fistula tract, but all with limited and debatable efficacy. Given the failure rate of all these options, new strategies are currently being evaluated. CONCLUSION: Anal fistulas in Crohn's disease are a real therapeutic challenge. New medical and surgical therapies are currently being evaluated, with promising results.

Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis.

The multifactorial basis of therapeutic response can obscure the relation between antimicrobial drug susceptibility and clinical outcome. To discern the relationship between parasite susceptibility to meglumine antimoniate (SbV) and therapeutic outcome of cutaneous leishmaniasis, risk factors for treatment failure were considered in evaluating this relationship in ninety-one cutaneous leishmaniasis patients and corresponding clinical strains of Leishmania (Viannia) panamensis. Parasite susceptibility to 32 µg SbV/mL (plasma Cmax) was evaluated in primary human macrophages, PBMCs, and U937 macrophages. Early parasitological response to treatment was determined in lesions of a subgroup of patients, and pathogenicity of Sb-resistant and sensitive clinical strains was compared in BALB/c mice. Parasite survival in cell models and patient lesions was determined by qRT-PCR of Leishmania 7SLRNA transcript. Parasite loads in BALB/c mice were quantified by limiting dilution analysis. The disparate Sb-susceptibility of parasite subpopulations distinguished by isoenzyme profiles (zymodemes) was manifest in all cell models. Notably, Sb-resistance defined by parasite survival, was most effectively discerned in U937 macrophages compared with primary human host cells, significantly higher among strains from patients who failed treatment than cured and, significantly associated with treatment failure. Each unit increase in transformed survival rate corresponded to a 10.6-fold rise in the odds of treatment failure. Furthermore, treatment failure was significantly associated with naturally Sb-resistant zymodeme 2.3 strains, which also produced larger lesions and parasite burdens in BALB/c mice than Sb-sensitive zymodeme 2.2 strains. The confounding effect of host risk factors for treatment failure in discerning this association was evidenced in comparing strains from patients with and without the defined risk factors for treatment failure. These results establish the association of natural resistance to meglumine antimoniate with treatment failure, the importance of host risk factors in evaluating drug susceptibility and treatment outcome, and the clinical and epidemiological relevance of natural Sb-resistance in L. (V.) panamensis subpopulations.

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Respiratory Rate Oxygenation (ROX) index as predictor of high flow nasal cannula in pediatric patients in pediatric intensive care unit.

BACKGROUND: High-flow nasal cannula (HFNC) is often used in pediatric populations with respiratory distress. In adults, the respiratory-rate oxygenation (ROX) index is used as a predictor of HFNC therapy; however, children have age-associated differences in respiratory rate, thus may not be applicable to children. This study aims to find the reliability of ROX index and modified P-ROX index as predictors of HFNC therapy failure in pediatric patients. METHODS: Subjects in this analytical cross-sectional study were taken from January 2023 until November 2023 in Cipto Mangunkusumo Hospital. Inclusion criteria are children aged 1 month to 18 years with respiratory distress and got HFNC therapy. Receiver operating characteristics (ROC) analysis was used to find mP-ROX index cutoff value as a predictor of HFNC failure. The area under curve (AUC) score of mP-ROX index was assessed at different time point. RESULTS: A total of 102 patients, with 70% of the population with pneumonia, were included in this study. There are significant differences in the ROX index between the successful and failed HFNC group therapy (p < 0.05). This study suggests that mP-ROX index is not useful as predictor of HFNC therapy in pediatrics. While ROX index < 5.52 at 60 min and < 5.68 at 90 min after HFNC initiation have a sensitivity of 90% and specificity of 71%, sensitivity of 78% and specificity of 76%, respectively. CONCLUSION: mP-ROX index is not useful as a predictor of HFNC therapy in pediatrics. Meanwhile, ROX index at 60 min and 90 min after initiation of HFNC is useful as a predictor of HFNC failure.

Risk factors for failing to complete gemcitabine-cisplatin neoadjuvant chemotherapy in muscle invasive bladder cancer patients.

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.

A nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis with renal anemia.

The determinants of roxadustat treatment failure in renal anemia remain elusive. This study sought to develop a nomogram for predicting the risk of treatment failure of roxadustat in peritoneal dialysis (PD) with renal anemia. A retrospective cohort analysis from January 1, 2019, to January 31, 2023, included 204 PD patients with renal anemia, stratified by attainment group (Hb ≥ 110 g/L, n = 103) or non-attainment (Hb < 110 g/L, n = 101) within 1 year treatment. Univariate and multivariate Cox proportional hazards regressions were employed to ascertain predictive factors and construct the nomogram. Nomogram efficacy was evaluated via C-index, time-dependent ROC, calibration plots, and decision curve analysis, with internal validation via tenfold cross-validation and 1000 bootstrap resampling iterations. The study identified PD duration, serum transferrin, cardiovascular comorbidities, and stains as significant predictors. The nomogram demonstrated moderate discrimination at 6 months (AUC: 0.717) and enhanced predictive accuracy at 12 months (AUC: 0.741). The predicted and actual risk probabilities were concordant, with clinical net benefits observed at six-month (8 to 53%) and twelve-month (27 to 84%) risk thresholds. This nomogram is a valuable tool for effectively predicting non-attainment risk and facilitating personalized management of renal anemia in PD patients treated with roxadustat.

The efficacy of machine learning models in forecasting treatment failure in thoracolumbar burst fractures treated with short-segment posterior spinal fixation.

BACKGROUND: Although short-segment posterior spinal fixation (SSPSF) has shown promising clinical outcomes in thoracolumbar burst fractures, the treatment may be prone to a relatively high failure rate. This study aimed to assess the effectiveness of machine learning models (MLMs) in predicting factors associated with treatment failure in thoracolumbar burst fractures treated with SSPSF. METHODS: A retrospective review of 332 consecutive patients with traumatic thoracolumbar burst fractures who underwent SSPSF at our institution between May 2016 and May 2023 was conducted. Patients were categorized into two groups based on treatment outcome (failure or non-failure). Potential risk factors for treatment failure were compared between the groups. Four MLMs, including random forest (RF), logistic regression (LR), support vector machine (SVM), and k-nearest neighborhood (k-NN), were employed to predict treatment failure. Additionally, LR and RF models were used to assess factors associated with treatment failure. RESULTS: Of the 332 included patients, 61.4% were male (n = 204), and treatment failure was observed in 44 patients (13.3%). Logistic regression analysis identified Load Sharing Classification (LSC) score, lack of index level instrumentation, and interpedicular distance (IPD) as factors associated with treatment failure (P < 0.05). All models demonstrated satisfactory performance. RF exhibited the highest accuracy in predicting treatment failure (accuracy = 0.948), followed by SVM (0.933), k-NN (0.927), and LR (0.917). Moreover, the RF model outperformed other models in terms of sensitivity and specificity (sensitivity = 0.863, specificity = 0.959). The area under the curve (AUC) for RF, LR, SVM, and k-NN was 0.911, 0.823, 0.844, and 0.877, respectively. CONCLUSIONS: This study demonstrated the utility of machine learning models in predicting treatment failure in thoracolumbar burst fractures treated with SSPSF. The findings support the potential of MLMs to predict treatment failure in this patient population, offering valuable prognostic information for early intervention and cost savings.

Low surgical weight associated with ETV failure in pediatric hydrocephalus patients.

The use of endoscopic third ventriculostomy (ETV) for treatment of pediatric hydrocephalus has higher failure rates in younger patients. Here we investigate the impact of select perioperative variables, specifically gestational age, chronological age, birth weight, and surgical weight, on ETV failure rates. A retrospective review was performed on patients treated with ETV - with or without choroid plexus cauterization (CPC) - from 2010 to 2021 at a large academic center. Analyses included Cox regression for independent predictors and Kaplan-Meier survival curves for time to-event outcomes. In total, 47 patients were treated with ETV; of these, 31 received adjunctive CPC. Overall, 66% of the cohort experienced ETV failure with a median failure of 36 days postoperatively. Patients aged < 6 months at time of surgery experienced 80% failure rate, and those > 6 months at time of surgery experienced a 41% failure rate. Univariate Cox regression analysis showed weight at the time of ETV surgery was significantly inversely associated with ETV failure with a hazard ratio of 0.92 (95% CI 0.82, 0.99). Multivariate analysis redemonstrated the inverse association of weight at time of surgery with ETV failure with hazard ratio of 0.76 (95% CI 0.60, 0.92), and sensitivity analysis showed < 4.9 kg as the optimal cutoff predicting ETV/CPC failure. Neither chronologic age nor gestational age were found to be significantly associated with ETV failure.In this study, younger patients experienced higher ETV failure rates, but multivariate regression found that weight was a more robust predictor of ETV failure than chronologic age or gestational age, with an optimal cutoff of 4.9 kg in our small cohort. Given the limited sample size, further study is needed to elucidate the independent role of weight as a peri-operative variable in determining ETV candidacy in young infants. Previous presentations: Poster Presentation, Congress of Neurological Surgeons.

Antibiotics for Acute Sinusitis in Children: A Meta-Analysis.

CONTEXT: Acute sinusitis is one of the leading causes of antibiotic prescriptions in children. No recent systematic reviews have examined the efficacy of antibiotics compared with placebo. OBJECTIVE: We sought to determine if antibiotics are superior to placebo in the treatment of acute sinusitis in children. DATA SOURCES: Medline and Embase were searched from their origin to July 2023. STUDY SELECTION: We considered randomized placebo-controlled studies focusing on the treatment of acute sinusitis. In all studies, symptoms were present for <4 weeks and subjects were <18 years of age. DATA EXTRACTION: Two authors independently extracted the data. We pooled data primarily using fixed-effects models. RESULTS: Analysis of 6 included studies showed that antibiotic treatment reduced the rate of treatment failure by 41% (with a risk ratio of 0.59; 95% confidence interval 0.49-0.72) compared with placebo. There was substantial heterogeneity between the studies (I2 = 69.7%), which decreased substantially when the 1 study with a high risk of bias was removed (I2 = 26.9%). Children treated with antibiotics were 1.6 times more likely to have diarrhea than those who were not treated with antibiotics (risk ratio = 1.62, 95% confidence interval 1.04-2.51). LIMITATIONS: A small number of studies were eligible for inclusion. Included studies differed in their methodology. CONCLUSIONS: In children with clinically diagnosed acute sinusitis, antibiotics significantly reduced the rate of treatment failure compared with placebo. However, given the favorable natural history of sinusitis, our results could also support close observation without immediate antibiotic treatment.

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study.

BACKGROUND: We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. METHODS: Personalised Anti-TNF therapy in Crohn's disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn's disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. FINDINGS: Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1-46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7-43·7), 34·4% (29·9-39·0), and 34·7% (29·8-39·5), and for adalimumab 35·9% (95% CI 31·2-40·5), 32·9% (26·8-39·2), and 28·9% (21·9-36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1-10·0 mg/L for infliximab and 10·1-12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4-38·2), 54·5% (49·4-59·0), and 60·0% (54·1-65·2), and for adalimumab 32·1% (26·7-37·1), 47·2% (40·2-53·4), and 68·4% (50·9-79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30-0·67], adalimumab: 0·39 [0·22-0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11-1·95]), obesity (vs not obese 1·62 [1·08-2·42]), baseline white cell count (1·06 [1·02-1·11) per 1 × 109 increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17-3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1-49·4) among patients treated with infliximab and 20·3% (13·8-26·2) among those treated with adalimumab. The development of anti-drug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31-0·52], adalimumab 0·42 [95% CI 0·24-0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13-1·88]) but not for adalimumab (HR 1·60 [0·92-2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20-3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11-2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. INTERPRETATION: Only around a third of patients with active luminal Crohn's disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs. FUNDING: Guts UK, Crohn's and Colitis UK, Cure Crohn's Colitis, AbbVie, Merck Sharp and Dohme, Napp Pharmaceuticals, Pfizer, and Celltrion Healthcare.