BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.
METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.
RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.
CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Post-surgery recurrence of meningiomas with multiple extracranial metastases is rare. Currently, information on extracranial metastases is limited, and no clear predictors and standardized treatment protocols can be applied clinically. Herein, we report a case of meningioma that recurred after two surgeries and had multiple distant metastases. Computed tomography revealed multiple enlarged lymph nodes in the para-aortic arch, left lower lung region, retroperitoneum, and abdominopelvic region, as well as soft tissue mass-like lesions under the liver capsule in the right lobe of the liver. Magnetic resonance imaging showed space-occupying lesions under the cranial plate of the left parietal lobe. Tissue biopsy confirmed the diagnosis of recurrent meningioma with extracranial metastases. Immune checkpoint inhibitors and anti-angiogenic drugs were administered. After two treatment cycles, the patient\'s clinical symptoms were significantly relieved, and the imaging assessment confirmed a stable disease. Although it did not meet our expectations, this combination therapy still demonstrated a possible benefit in improving meningioma patients\' survival and quality of life. In this report, along with the case, we also review the relevant literature on the subject and discuss the associated risk factors and treatment options.

The study of dementia and epilepsy may provide particular insight into behavioural alterations. We describe a rare case of ictal aggressive behaviour in a patient with focal epilepsy associated with a non-dominant dorso-lateral prefrontal lesion. During focal seizures, our patient showed intense agitation and anger, for a long time misinterpreted as psychogenic attacks, which disappeared after epilepsy surgery. The defined anatomical origin of such ictal emotional behaviour is not fully understood, however, the dorso-lateral prefrontal area appears to correlate less frequently with aggressiveness compared to the antero-mesial area. We describe the electroclinical data of our patient and provide a brief review of the mechanisms underlying aggressive conduct in epilepsy and dementia. An understanding of this mechanism could help to clarify the neural basis and treatment of violence associated with these and other neurological disorders. [Published with video sequence].

Oral submucous fibrosis (OSMF) is a potentially malignant disorder, characterized by alteration in the connective tissue stroma. Its association with oral squamous cell carcinoma (OSCC) has been recognized and conferred a special status as a distinct disease entity with improved prognosis as compared to conventional squamous cell carcinoma. Such cases of concomitant presentation of OSMF and OSCC have not yet been defined, leading to ambiguity regarding the evaluation. The concomitant occurrence of OSMF-OSCC is associated with histopathological features, unlike OSMF, yet similar to an aggressive presentation of OSCC. An indepth evaluation of the connective tissue, along with other tumor characteristics such as tissue hypoxia, inflammatory cell population, neoangiogenesis, and stromal cells fortify the possibility of these cases of concomitance being as aggressive, if not more, as compared to conventional OSCC. Thus, recognizing such cases along with the evaluation of probable prognostic indicators is necessary to improve the current understanding of tumorigenesis and progression in concomitant cases of OSMF-OSCC.

Chondroblastomas are a primary benign cartilaginous tumor that accounts for approximately 1% of all benign bone tumors. Primarily they are treated by curettage. The patient presented 4 years after a successfully treated chondroblastoma (curettage and Bone cement). Wide resection of the proximal tibia with endoprosthesis replacement was done. Lung CT showed multiple lung metastasis and despite starting chemotherapy, he succumbed to the disease. We discuss regarding the possibilities of \"aggressive\" chondroblastoma and more recently termed chondroblastoma-like osteosarcoma which is a separate entity from chondroblastoma. Aggressiveness in chondroblastoma can be 1 of 3 types as follows: 1. benign chondroblastoma with lung metastasis. 2. malignant chondroblastoma. 3. subsequent malignant transformation of benign chondroblastoma. We have attempted to review the literature and describe the \"aggressive\" chondroblastoma and chondroblastoma-like osteosarcoma in this report.

The cytotoxic agent, eribulin represents a new standard of care in the treatment of heavily pretreated metastatic breast cancer patients. Here, we describe our experience with eribulin in a patient with a controlled primary breast cancer, who showed an aggressive recurrence of the primary tumor, including metastatic disease. Treatment management of the second primary tumor included six lines of chemotherapy and three lines of hormonal therapy, including eribulin as sixth line among all chemotherapies received. Eribulin treatment achieved a fast response to all metastatic sites and decelerated the aggressive evolution of the second disease.

Recent evidence suggests that a pro-inflammatory diet could be associated with prostate cancer (PC) risk. To evaluate the association between dietary inflammatory index (DII) and PC risk as well as aggressiveness, we conducted a case-control study in Mexico City. Cases were 394 individuals with incident, histologically confirmed PC, who were matched by age (±5 years) with 794 population controls. Dietary information was obtained through a semi-quantitative FFQ with a 3-year frame of reference before diagnosis, for cases, or interview, for controls. On the basis of twenty-eight food parameters, we estimated the energy-adjusted DII (E-DII). According to the Gleason score at diagnosis, PC cases were categorised as high (≥8), moderate (=7) and low (≤6) PC risk. Independent, unconditional logistic regression models adjusted for potential confounders were used to estimate PC risk and PC aggressiveness. There were no significant associations between overall PC risk and E-DII (OR3rd v. 1st tertile 1·18; 95 % CI 0·85, 1·63; P=0·33) or among men with high-risk PC (Gleason≥8) (OR 1·46; 95 % CI 0·88, 2·42; P=0·14). These results do not support the hypothesis that a pro-inflammatory diet is related to PC risk and PC aggressiveness. However, further studies with larger sample sizes, with sufficient statistical power and of varying designs should be conducted to address this hypothesis.

When a patient arrives at the Emergency Room with acute myocardial infarction (AMI), the provider on duty must quickly decide how aggressively the patient should be treated. Using Florida data on all such patients from 1992 to 2014, we decompose practice style into two components: The provider\'s probability of conducting invasive procedures on the average patient (which we characterize as aggressiveness), and the responsiveness of the choice of procedure to the patient\'s characteristics. We show that within hospitals and years, patients with more aggressive providers have consistently higher costs and better outcomes. Since all patients benefit from higher utilization of invasive procedures, targeting procedure use to the most appropriate patients benefits these patients at the expense of the less appropriate patients. We also find that the most aggressive and responsive physicians are young, male, and trained in top 20 schools.

BACKGROUND: Yokukan-san, a Japanese traditional herbal (Kampo) prescription, has recently gathered increasing attention due to accumulating reports showing its remarkable efficacy in treating a wide variety of diseases refractory to conventional medicine as well as the behavioral and psychological symptoms of dementia. As yokukan-san has become broadly integrated with conventional medicine, augmentation therapy with other Kampo prescriptions has become necessary when the yokukan-san has been only partially efficacious. In this paper, we report three cases in which the addition of orengedoku-to, another Kampo formula, to yokukan-san was remarkably effective.
METHODS: Case 1 was an 85-year-old man with Alzheimer-type dementia who had become aggressive during the past 2 years. Three milligrams of aripiprazole completely suppressed his problematic behaviors but had to be stopped because of extrapyramidal symptoms. In the second case, a 44-year-old man with methamphetamine-induced psychosis had suffered from serious tardive dystonia for 2 years. No conventional approach had improved his tardive dystonia. The third case was a 29-year-old engineer who often failed to resist aggressive impulses and was diagnosed with intermittent explosive disorder. He was prescribed 5 mg of olanzapine, which did not suppress his extraordinary anger and caused somnolence even though the dose was low.
RESULTS: Yokukan-san was complementarily added to the patients\' regular medication and exerted a definitive but partial effect in all cases. The addition of orengedoku-to to yokukan-san exerted the same efficacy as aripiprazole in controlling aggressiveness in Case 1, improved the tardive dystonia by 80% in Case 2, and was completely effective in controlling the patient\'s aggressive impulses in Case 3.
CONCLUSIONS: Together with empirical evidence demonstrating the effectiveness of both yokukansan and orengedoku-to in reducing irritability, impulsivity, and aggression, these three cases suggest that orengedoku-to augmentation can be an effective option in cases that are partially responsive to yokukan-san treatment.