The impact of spleen volume on the survival of metastatic pancreatic adenocarcinoma patients receiving nanoliposomal irinotecan

Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (NalFL) comprises the current standard for gemcitabine-failed metastatic pancreatic ductal adenocarcinoma (PDAC). As liposomes generally accumulate in the spleen, we evaluated the impact of spleen volume on prognosis. We enrolled patients with metastatic PDAC who failed gemcitabine-based therapy and were initiated on NalFL between August 2018 and November 2020. The spleen volume before NalFL administration was evaluated. They were stratified into dose subgroups (i.e. low, < 48 mg/m²; intermediate, 48 - < 64 mg/m²; high, ≥ 64 mg/m²) by the average nal-IRI dose during the entire treatment, and multivariate analysis of overall survival (OS) was performed. We included 547 patients with a median age of 63 years (range, 27-89 years) and a median of 1 (range, 0-7) palliative chemotherapy regimen. The median spleen volume was 245 mL (range, 82-817 mL). Among patients with splenomegaly (≥ 245 mL), the low-dose subgroup had the worst median time to treatment failure (TTF, 1.8 months vs. 2.5 months vs. 2.5 months, P = 0.020) and OS (3.3 months vs. 5.9 months vs. 6.6 months, P = 0.018) as against no prognostic impact in patients without splenomegaly. In the multivariate analysis of patients with splenomegaly, performance status (PS) ≥ 2, body surface area (BSA) < 1.6 m², prior fluoropyrimidine use, liver metastasis, and low-dose subgroup were independent poor prognostic factors. A low average nal-IRI dose was significantly associated with poor prognosis, especially among patients with splenomegaly. Further pharmacological studies should validate the relevance of spleen volume on the treatment outcomes of nal-IRI.     

重症肌无力合并胸腺瘤的外科治疗

目的探讨重症肌无力(MG)合并胸腺瘤的外科治疗方法。方法对24例MG合并胸腺瘤患者的临床资料进行回顾性分析与总结。结果全组均行手术切除胸腺瘤,其中完整切除23例,部分切除1例。术后死亡1例,随访1~5年,手术效果较好。结论胸腺切除是重症肌无力合并胸腺瘤迄今公认的治疗手段,如尽早手术治疗,将能获得较好的疗效。     

Prediction of the Uric Acid Component in Nephrolithiasis Using Simple Clinical Information about Metabolic Disorder and Obesity: A Machine Learning-Based Model

There is a great need for a diagnostic tool using simple clinical information collected from patients to diagnose uric acid (UA) stones in nephrolithiasis. We built a predictive model making use of machine learning (ML) methodologies entering simple parameters easily obtained at the initial clinical visit. Socio-demographic, health, and clinical data from two cohorts (A and B), both diagnosed with nephrolithiasis, one between 2012 and 2016 and the other between June and December 2020, were collected before nephrolithiasis treatment. A ML-based model for predicting UA stones in nephrolithiasis was developed using eight simple parameters—sex, age, gout, diabetes mellitus, body mass index, estimated glomerular filtration rate, bacteriuria, and urine pH. Data from Cohort A were used for model training and validation (ratio 3:2), while data from Cohort B were used only for validation. One hundred and forty-six (13.3%) out of 1098 patients in Cohort A and 3 (4.23%) out of 71 patients in Cohort B had pure UA stones. For Cohort A, our model achieved a validation AUC (area under ROC curve) of 0.842, with 0.8475 sensitivity and 0.748 specificity. For Cohort B, our model achieved 0.936 AUC, with 1.0 sensitivity, and 0.912 specificity. This ML-based model provides a convenient and reliable method for diagnosing urolithiasis. Using only eight readily available clinical parameters, including information about metabolic disorder and obesity, it distinguished pure uric acid stones from other stones before treatment.     

Limb salvage of infected diabetic foot ulcers with microsurgical free-muscle transfer

This study was comprised of 9 diabetic patients with 10 infected foot ulcers, including osteomyelitis in 4 limbs and gangrene in 3 limbs. Adequate debridement of these complicated wounds inevitably resulted in exposure of bones or tendons. All defects were successfully reconstructed with free gracilis muscle flaps covered with split-thickness skin grafts. No recurrence of ulcer or infection was noted in the muscle-transplanted area during the follow-up period. Laser Doppler perfusion monitor measurement showed that the perfusion unit of the denervated free muscle flap increased to a peak at the second week after transplantation; the neovascularization of the grafted skin, the progressive decrease of the muscle swelling, and the decreased interstitial pressure may be the main contributing factors. The perfusion unit of the muscle flap reached equilibrium with the surrounding tissue at about 8 weeks after microsurgical transfer. Lower extremity amputation is a major health problem in the diabetic population. The microvascular free-muscle transfer was proved to play an effective and important role in limb salvage in diabetic patients with infected foot ulcers. The gracilis muscle flap was recommended due to its lack of bulkiness and minimal donor site deformity.     

Radiofrequency Ablation of Hepatic Metastases: Factors Influencing Local Tumor Progression

Background

Although radiofrequency ablation (RFA) of nonresectable hepatic metastases has gained wide acceptance by showing survival benefit in selected patients, scattered reports are available regarding risk factors of local control of percutaneous RFA. The purpose of this study was to prospectively evaluate the factors influencing local tumor progression after percutaneous RFA of hepatic metastases.

Methods

Sixty-nine hepatic metastatic lesions in 54 patients were treated by percutaneous RFA. Efficacy was evaluated by contrast-enhanced computed tomography or magnetic resonance imaging at 1 month after ablation, then at 3-month intervals for the first year and biannually thereafter.

Results

The results of the log-rank test showed that tumor size of <3 cm (p = 0.024) and the absence of tumor contiguous with large vessels (p = 0.002) significantly correlated with local control for hepatic metastases. Cox regression analysis showed that the tumor size <3 cm and the absence of tumor contiguous with large vessels were independent factors (p = 0.055 and 0.009, respectively). The results of the log-rank test showed that neither the threshold post-ablation margin of 1.8 cm (p = 0.064) nor the presence of a tumor with subcapsular location (p = 0.134) correlated with the success of local control.

Conclusions

Percutaneous RFA is more effective in achieving local control in patients with hepatic metastases when the tumor size is <3 cm and not contiguous with large vessels.     

A systematic review on the effectiveness of sex offender risk assessment tools in predicting sexual recidivism of adult male sex offenders

PurposeThis study aimed to systematically review the effectiveness of risk assessment tools in predicting sexual recidivism of adult male offenders.BackgroundSex offender risk assessment aids risk management within the criminal justice system. Some tools follow an actuarial approach and some adopt structured professional judgement. There has not been a systematic review evaluating and comparing the effectiveness of those tools and appraising the overall quality of the primary research.MethodsSix electronic databases and reference lists of relevant meta-analyses were searched. Three experts were contacted to obtain relevant studies. Inclusion criteria were applied to the identified references and the included studies were quality assessed, using pre-defined criteria, prior to data extraction and synthesis.ResultsElectronic search yielded 4949 hits. Of these, 1419 duplicates, 1 meta-analysis and 3382 irrelevant hits were excluded. 14 publications identified from previous meta-analyses were included. 2 non-English language duplications of publications were excluded. 89 publications that did not meet inclusion criteria and 15 inaccessible publications were excluded. 11 studies that did not meet minimum threshold criteria and 1 study that re-analysed an already included sample were then excluded, leaving 43 publications containing 43 studies.ConclusionsAll included tools demonstrated at least moderate predictive accuracy, with two reporting a large effect size (VRS-SO and SRA), although these two came under much less empirical scrutiny than the others and may have been the subject of developer bias in the research that is available. The VRS-SO was found to have the highest mean quality score, this again being limited by the number of studies and developer bias. The quality of the primary research is variable. More independent high quality research is needed, particularly on structured professional judgement incorporating dynamic risk factors.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.     

Hyaluronic acid‐dependent protection against UVB‐damaged human corneal cells

Within ultraviolet radiation, ultraviolet B (UVB) is the most energetic and damaging to humans. At the protein level, UVB irradiation downregulates the expression of antioxidant enzymes leading to the accumulation of reactive oxygen species (ROS). Due to lacking of a global analysis of UVB‐modulated corneal proteome, we investigate in vitro the mechanism of UVB‐induced corneal damage to determine whether hyaluronic acid (HA) is able to reduce UVB irradiation‐induced injury in human corneal epithelial cells. Accordingly, human corneal epithelial cell lines (HCE‐2) were irradiated with UVB, followed by incubation with low molecular weight HA (LMW‐HA, 100 kDa) or high molecular weight HA (HMW‐HA, 1,000 kDa) to investigate the physiologic protection of HMW‐HA in UVB‐induced corneal injury, and to perform a global proteomic analysis. The data demonstrated that HA treatment protects corneal epithelial cells in the UVB‐induced wound model, and that the molecular weight of HA is a crucial factor. Only HMW‐HA significantly reduces the UVB‐induced cytotoxic effects in corneal cells and increases cell migration and wound‐healing ability. In addition, proteomic analysis showed that HMW‐HA might modulate cytoskeleton regulation, signal transduction, biosynthesis, redox regulation, and protein folding to stimulate wound healing and to prevent these UVB‐damaged cells from cell death. Further studies evidenced membrane‐associated progesterone receptor component 1 (mPR) and malate dehydrogenase (MDH2) play essential roles in protecting corneal cells from UVB irradiation. This study reports on UVB‐modulated cellular proteins that might play an important role in UVB‐induced corneal cell injury and show HMW‐HA to be a potential substance for protecting corneal cells from UVB‐induced injury. Environ. Mol. Mutagen. 54:429–449, 2013. © 2013 Wiley Periodicals, Inc.