Comparisons of characteristics and outcome between abusive head trauma and non-abusive head trauma in a pediatric intensive care unit.

BACKGROUND: Abusive head trauma (AHT) is the leading cause of death in infants with traumatic brain injury (TBI). Early recognition of AHT is important for improving outcomes, but it can be challenging due to its similar presentations with non-abusive head trauma (nAHT). This study aims to compare clinical presentations and outcomes between infants with AHT and nAHT, and to identify the risk factors for poor outcomes of AHT. METHODS: We retrospectively analyzed infants of TBI in our pediatric intensive care unit from January 2014 to December 2020. Clinical manifestations and outcomes were compared between patients with AHT and nAHT. Risk factors for poor outcomes in AHT patients were also analyzed. RESULTS: 60 patients were enrolled for this analysis, including 18 of AHT (30%) and 42 of nAHT (70%). Compared with those with nAHT, patients with AHT were more likely to have conscious change, seizures, limb weakness, and respiratory failure, but with a fewer incidence of skull fractures. Additionally, clinical outcomes of AHT patients were worse, with more cases undergoing neurosurgery, higher Pediatric Overall Performance Category score at discharge, and more anti-epileptic drug (AED) use after discharge. For AHT patients, conscious change is an independent risk factor for a composite poor outcome of mortality, ventilator dependence, or AED use (OR = 21.9, P = 0.04) CONCLUSION: AHT has a worse outcome than nAHT. Conscious change, seizures and limb weaknesses but not skull fractures are more common in AHT. Conscious change is both an early reminder of AHT and a risk factor for its poor outcomes.

Experience with outreach services of a multidisciplinary team for child abuse identification.

BACKGROUND/PURPOSE: Identifying child abuse is sometimes challenging due to its various presentations. To facilitate timely identification of critical or complex cases of physical abuse outside our child protection center, we established an outreach multidisciplinary team (OMDT) to support Kaohsiung City Government in 2014. The objective of this study was to describe our experience of OMDT services during a 6-year period and examine its role in assisting law enforcement. METHODS: We retrospectively analyzed all OMDT cases from January 2014 to January 2020. Clinical characteristics and OMDT reports were reviewed. After inspection by our OMDT, cases were determined as indicating either a high risk or low risk of child abuse. Associations among clinical characteristics, radiographic findings, OMDT decisions and case outcomes including law enforcement and prosecution were examined. RESULTS: Thirty-two cases (22 [68.8%] males and 10 [31.2%] females; mean age 24.2 months) received OMDT service, of whom 28 (87.5%) were admitted to the pediatric intensive care unit. The victims had an average of 2.2 types of wounds in 3.4 locations. The most common finding on radiography was subdural hemorrhage (18, 56.3%), followed by subarachnoid hemorrhage (31, 31.3%). Law enforcement was activated in 20 (64.5%) cases, and was only associated with the high-risk group as determined by the OMDT (p < 0.05) but not with any other variables. CONCLUSION: Our experience indicates that an OMDT can play an important role in child protection and activating law enforcement for children with complex or critical physical abuse. We suggest that in Taiwan, OMDT services should be incorporated into child protection centers, National Health Insurance system and governmental child protection policies.

A common regulatory variant in SLC35B4 influences the recurrence and survival of prostate cancer.

Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome-wide experimental findings. Overall, 131 putative regulatory SNPs with the highest confidence score on predicted functionality were investigated in two independent localized prostate cancer cohorts totalling 458 patients who underwent radical prostatectomy. The statistically significant SNPs identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNPs, rs1646724, that are consistently associated with increased risk of recurrence in localized disease (P = .003) and mortality in patients with advanced prostate cancer (P = .032) after adjusting for known clinicopathological factors. Further investigation revealed that rs1646724 may affect expression of SLC35B4, which encodes a glycosyltransferase, and that down-regulation of SLC35B4 by transfecting short hairpin RNA in DU145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC35B4 expression correlated with more aggressive forms of prostate cancer and poor patient prognosis. Our study provides robust evidence that regulatory genetic variants can affect clinical outcomes.

Topiramate-associated sexual dysfunction: A systematic review.

INTRODUCTION: Sexual pharmacotoxicity renders patients with epilepsy at a risk for sexual dysfunction (SD). This study is aimed to analyze the relationship between sexual function and topiramate to avoid topiramate-associated SD. METHODS: A systematic review following the PRISMA guidelines was performed to elucidate any SD occurrence in patients receiving topiramate. RESULTS: A total of 17 publications were reviewed. Based on limited polytherapy observational studies, the frequency of self-reported topiramate-associated SD, libido disorder, and orgasmic disorder in patients with polytherapy was 9.0%, 9.0%, and 2.6%, respectively (grade C evidence). Female patients mainly had anorgasmia, whereas male patients principally had erectile dysfunction. The daily dose of topiramate in patients with SD was within the recommended dose. Sexual adversity usually occurred from 4weeks after topiramate use but favorably subsided without eventful complications after topiramate substitution or dose reduction in all patients. CONCLUSIONS: Topiramate can elicit different patterns of SD, especially anorgasmia in women and erectile dysfunction in men, even with a therapeutic dose. Detailed drug education and careful monitoring are necessary to maximize sexual health, especially in persons undergoing polytherapy and with other risks for SD. Moreover, a rapid response, such as substitution or reduction of the dose, is suggested when SD occurs during its use.

Cancer Stem Cell Gene Variants Predict Disease Recurrence in Patients Treated with Radical Prostatectomy for Prostate Cancer.

Background: Cancer stem cells (CSCs) are involved in tumor progression and drug resistance. We hypothesized that variants in CSC marker genes influence treatment outcomes in prostate cancer. Methods: Ten potentially functional single nucleotide polymorphisms (SNPs) in seven prostate CSC marker genes, TACSTD2, PROM1, ITGA2, POU5F1, EZH2, PSCA, and CD44, were selected for analysis of their association with disease recurrence by Kaplan-Meier analysis and Cox regression in a cohort of 320 patients with localized prostate cancer receiving radical prostatectomy. Results: We identified one independent SNP, rs2394882, in POU5F1 that was associated with prostate cancer recurrence (hazard ratio 0.32, 95% confidence interval 0.14-0.71, P = 0.005) after adjustment for known clinical predictors. Further in silico functional analyses revealed that rs2394882 affects POU5F1 expression, which in turn is significantly correlated with prostate cancer aggressiveness and patient prognosis. Conclusion: Our results suggest that rs2394882 is prognostically relevant in prostate cancer, possibly by modulating the expression of the CSC gene POU5F1.

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy.

UNLABELLED: Backgroud: Increasing evidence suggests the involvement of chronic inflammation in the progression of prostate cancer, and prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase-2, catalyzes the rate-limiting steps of the pathway. We hypothesized that genetic variants of PTGS2 can influence the outcome of prostate cancer patients. METHODS: We genotyped five haplotype-tagging single-nucleotide polymorphisms (SNPs) to detect common genetic variations across the PTGS2 region in 458 prostate cancer patients treated with radical prostatectomy. RESULTS: One SNP, rs4648302, was associated with disease recurrence. Five-year recurrence-free survival rate increased according to the number of variant alleles inherited (55.6%, 70.7%, and 100.0% for patients with different genotypes; P = 0.037), and the effect was maintained in multivariable analysis. Public dataset analyses also suggested that PTGS2 expression was correlated with prostate cancer prognosis. CONCLUSION: Our results indicated that PTGS2 could be a potential prognostic marker to improve the prediction of disease recurrence in prostate cancer patients.

Inherited Variants in Wnt Pathway Genes Influence Outcomes of Prostate Cancer Patients Receiving Androgen Deprivation Therapy.

Aberrant Wnt signaling has been associated with many types of cancer. However, the association of inherited Wnt pathway variants with clinical outcomes in prostate cancer patients receiving androgen deprivation therapy (ADT) has not been determined. Here, we comprehensively studied the contribution of common single nucleotide polymorphisms (SNPs) in Wnt pathway genes to the clinical outcomes of 465 advanced prostate cancer patients treated with ADT. Two SNPs, adenomatous polyposis coli (APC) rs2707765 and rs497844, were significantly (p ≤ 0.009 and q ≤ 0.043) associated with both prostate cancer progression and all-cause mortality, even after multivariate analyses and multiple testing correction. Patients with a greater number of favorable alleles had a longer time to disease progression and better overall survival during ADT (p for trend ≤ 0.003). Additional, cDNA array and in silico analyses of prostate cancer tissue suggested that rs2707765 affects APC expression, which in turn is correlated with tumor aggressiveness and patient prognosis. This study identifies the influence of inherited variants in the Wnt pathway on the efficacy of ADT and highlights a preclinical rationale for using APC as a prognostic marker in advanced prostate cancer.

Prognostic Relevance of Methylenetetrahydrofolate Reductase Polymorphisms for Prostate Cancer.

Folate metabolism has been associated with cancers via alterations in nucleotide synthesis, DNA methylation, and DNA repair. We hypothesized that genetic variants in methylenetetrahydrofolate reductase (MTHFR), a key enzyme of folate metabolism, would affect the prognosis of prostate cancer. Three haplotype-tagging single-nucleotide polymorphisms (SNPs) across the MTHFR gene region were genotyped in a cohort of 458 patients with clinically localized prostate cancer treated with radical prostatectomy. One SNP, rs9651118, was associated with disease recurrence, and the association persisted after multivariate analyses adjusting for known risk factors. Public dataset analyses suggested that rs9651118 affects MTHFR expression. Quantitative real-time polymerase chain reaction analysis revealed that MTHFR expression is significantly upregulated in prostate tumor tissues when compared with adjacent normal tissues. Furthermore, overexpression of MTHFR correlates with cancer recurrence and death in two independent publicly available prostate cancer datasets. In conclusion, our data provide rationale to further validate the clinical utility of MTHFR rs9651118 as a biomarker for prognosis in prostate cancer.

ß1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.

Triple negative breast cancer (TNBC) displays higher risk of recurrence and distant metastasis. Due to absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), TNBC lacks clinically established targeted therapies. Therefore, understanding of the mechanism underlying the aggressive behaviors of TNBC is required for the design of individualized strategies and the elongation of overall survival duration. Here, we supported a positive correlation between ß1 integrin and malignant behaviors such as cell migration, invasion, and drug resistance. We found that silencing of ß1 integrin inhibited cell migration, invasion, and increased the sensitivity to anti-cancer drug. In contrast, activation of ß1 integrin increased cell migration, invasion, and decreased the sensitivity to anti-cancer drug. Furthermore, we found that silencing of ß1 integrin abolished Focal adhesion kinese (FAK) mediated cell survival. Overexpression of FAK could restore cisplatin-induced apoptosis in ß1 integrin-depleted cells. Consistent to in vitro data, ß1 integrin expression was also positively correlated with FAK (p = 0.031) in clinical tissue. More importantly, ß1 integrin expression was significantly correlated with patient outcome. In summary, our study indicated that ß1 integrin could regulate TNBC cells migration, invasion, drug sensitivity, and be a potential prognostic biomarker in TNBC patient survival.

Antiphospholipid antibodies and cerebellar ataxia: a clinical analysis and literature review.

BACKGROUND: Although it has been established that antiphospholipid antibodies (APAbs) bind to and modulate the signaling of cerebellar neurons in vitro, the clinical correlation between increased APAbs and cerebellar ataxia has rarely been investigated. METHODS: We reviewed 10 patients presenting with cerebellar ataxia with increased blood APAbs from our database along with 3 APAb-associated cerebellar ataxia patients in the literature. RESULTS: Of these 10 patients, 4 exhibited a subacute onset of progressive ataxia, and there were no significant structural changes in their brains that appeared to be responsible for the symptoms. Another 6 showed a chronic course of ataxia, and shared similar morphological changes that included symmetrical lesions in bilateral hemispheres, periventricular lucency and central and temporal atrophy of varying severity; the cerebellum was spared. The predominant APAbs for subacute and chronic ataxia were the anti-beta2-glycoprotein I antibody and anticardiolipin antibody, respectively. Cancer was found in 1 patient with subacute ataxia and in 4 with chronic ataxia. The removal of the cancer, the plasmapheresis and immunosuppressive therapy successfully abolished the ataxia and increased APAb levels in all 5 patients. CONCLUSIONS: The relation between APAbs and nonvascular neurological disorders, such as cerebellar ataxia, should be further studied. APAbs may mediate neurological deficits via different mechanisms such as structural damage or functional neurotoxicity. Clinically, the examination of blood APAb levels is recommended for patients with cerebellar ataxia without a determined cause, and the further survey of systemic cancers in the case of APAb positivity is also recommended. Finally, plasmapheresis is a reasonable and effective treatment for APAb-associated cerebellar ataxia.

Periodic drop thumb, hypokalemia and adrenal adenoma.

OBJECTIVE: To report an unusual involvement of focal distal muscles but not proximal muscles in a patient with hypokalemic periodic paralysis (hypoPP). CLINICAL PRESENTATION AND INTERVENTION: A middle-aged woman presented with episodic weakness of the bilateral thumbs lasting for 2 years. Hypokalemia and a left adrenal mass were subsequently found. Her weakness subsided after surgical removal of the adrenal mass, which was pathologically proven to be an adrenal adenoma. CONCLUSION: The findings for this patient should alert physicians to consider focal distal motor paresis due to hypoPP. A preexisting occult trauma may predispose to paralysis at an atypical location in secondary hypoPP.

Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.

Although a previous or recent history of varicella-zoster virus (VZV) infection is known to increase the risk of stroke in both children and adults, the influence of zoster sine herpetic remains unclear. We report an immunocompetent man with common cold symptoms and conjunctivitis, followed by an acute onset of bulbar weakness and hemihypesthesia without preceding skin rash. Acute medullary infarction and left vertebral artery stenosis were detected. VZV infection was finally identified. Zoster sine herpetic interferes with accurate diagnosis of infectious stroke, and vertebral artery involvement is unusual in ischemic stroke in this situation. An unexplained course of ischemic stroke event should be suspected in patients with VZV cerebrovasculopathy, especially in those without conventional stroke risk factors and those exhibiting concomitant infectious complications.

The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Successful amelioration of tinnitus in a stroke patient by low-dose gabapentin.

Bilaterally progressive tinnitus and hearing impairment occurred in a hypertensive patient shortly after an episode of right ganglionic hemorrhage. Audiometric tests showed a mixed sensorineural and conduction hearing loss. When low-dose gabapentin was administrated for the pre-existing postherpetic thoracic neuralgia, the tinnitus dramatically improved but recurred after discontinuation of the drug. Hearing function did not change. In view of a controversy of gabapentin and tinnitus in previous trials, the findings in this patient support that low-dose gabapentin benefits the subgroup of tinnitus patients with secondary contributing factors, such as stroke.

Ischemic stroke after low-voltage electric injury in a diabetic and coagulopathic woman.

Electric injury is a common physical injury in daily life. Because of the low resistance of vascular tissue, vascular injury and thrombosis are frequently found in cases of high-voltage electric injury but are rarely reported in low-voltage conditions. We present the case of a diabetic woman who suffered symptomatic brainstem stroke after a short duration of 60 Hz/110 V alternate current electric contact with a home washer socket. A stroke risk factor survey did not reveal remarkable cardiac or vascular abnormality, except increased glycohemoglobin levels and decreased protein C activity. In contrast to a direct and adequate energy transfer in high-voltage electric injury, a pre-existing vasculohemostatic deficit, such as coagulopathy, has been proposed to provide a predisposition to thrombosis in low-voltage electric injury. Nevertheless, the findings in this patient remind the possibility of physical triggering factor for stroke occurrence in our environment as new technology and product generates rapidly enough for understanding their safety and biologic effect.

Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Correlation With CD4 Levels in a Patient With HIV Infection.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare tumor found in immunocompromised patients, and its treatment is not well-established. A role for antiretroviral therapy in human immunodeficiency virus (HIV)-related EBV-SMT has been proposed; however, the relevance of tumor size, CD4 levels, and immune reconstitution inflammatory syndrome (IRIS) has not been previously reported. We present the first case, to our knowledge, of a tumor that shrank in association with elevated CD4 counts. IRIS occurred in this case following antiretroviral therapy. This finding highlights the importance of the immune response in HIV-related EBV-SMT.

Unique Pulmonary Hypertension in Young Children: A Case Series Study.

Pediatric pulmonary hypertension (PH) has a similar clinical presentation to the adult disease but is associated with several additional disorders and challenges that require a specific approach for their fulminant course. With improved care for premature infants, various forms of pulmonary vascular disease have been found in children that did not previously exist. Pediatric PH can begin in utero, resulting in pulmonary vascularity growth abnormalities that may persist into adulthood. Here, we retrospectively reviewed several unique pediatric PH cases from 2000 to 2020 at Kaohsiung Medical University Hospital, Taiwan, a tertiary teaching hospital. Their comorbidities varied and included surfactant dysfunction, bronchopulmonary dysplasia, premature closure of the ductus arteriosus, high levels of renin and aldosterone, and Swyer-James-Macleod syndrome. Their clinical profiles, radiological characteristics, echocardiography, pulmonary angiogram, and therapeutic regimens were recorded. Further, because the underlying causes of pediatric PH were complex and markedly different according to age, adult PH classification may not be applicable to pediatric PH in all settings. We also classified these cases using different systems, including the Panama classification and the Sixth World Symposium on PH, and compared their advantages and disadvantages.

Symptomatic noncompressive motoromyelopathy presents as early manifestation in ankylosing spondylitis.

Ankylosing spondylitis (AS) is an autoimmune spondyloarthropathy involving principally the sacroiliac joint and axial skeleton. Spinal cord involvement is an infrequent and late complication. It mostly results from compressive myelopathy due to skeletal osteopathy and usually presents with radiculomyelopathic sensory and motor deficits. To report three patients who suffered a progressive paraparesis/tetraparesis compatible with motor myelopathy without typical skeletal symptom. Myelopathy of unknown origin was initially interpreted in these patients. Radiography did not show typical change at sacroiliac joint or vertebrate. Spinal magnetic resonance image revealed cord atrophy at cervical and thoracic segment. A positivity of B27 antigen was found afterward. Their spondyloarthropathic symptoms developed within six months later with radiographic sacroiliitis. Seropositive AS with noncompressive myelopathy was finally established. Patients showed a reverse of motor impairment when their pain was well undercontrolled. Motor myelopathy may be neglected or underestimated in AS, in especially when typical skeletal symptom is absent or minimal. It may progress surreptitiously to harm spinal function or superimpose to crippling disability in compressive spinal cord injury. Therefore, a careful evaluation and monitor of spinal cord function is important for AS patient despite spinal deformity is not observed.

Spinal cheiro-oral syndrome: a common neurological entity in an unusual site.

BACKGROUND AND PURPOSE: Cheiro-oral syndrome (COS) is an established neurological entity characterized by a sensory impairment confined to the mouth angle and ipsilateral finger(s)/ hand. The current understanding of localization is a concomitant involvement of the spinothalamic and trigeminothalamic tract between the cortex and pons. The cervical spinal cord has not been mentioned in this situation yet, and this unusual location may heretofore increase the risk of misdiagnosis. MATERIAL AND METHODS: Six patients who presented with unilateral COS due to cervical cord disorder are reported. RESULTS: All patients were women and their age ranged between 42 and 70 years. Their neurological deficits included unilateral paraesthesiae restricted to cheirooral distribution, positive radicular sign, and mild change of tendon reflex. Cervical spinal stenosis at middle/lower cervical spine with variable magnitude of cord compression and intrinsic cord damage was found. A diagnostic dilemma obviously arises from the lack of tangible neurological signs or typical pattern of myelopathy, in addition to the previous concept of cerebral involvement. A benign course ensued in all reported patients. CONCLUSIONS: Cheiro-oral syndrome can be an early neurological sign for cervical cord disorder; it further suggests that it is a strong neurological but weak localizing sign. A reciprocal influence of multiple factors is considered to generate COS at the cervical cord. Therefore, an absence of brain pathology should lead to a thorough examination of the cervical cord in case of COS.

Primary clear cell adenocarcinoma of prostate: A diagnostic challenge.

Clear cell adenocarcinoma (CCA) rarely occurs in men, not to mention in prostate. We reported a 44-year-old male patient who suffered from recurrent dysuria and frequency for 6 months. Transurethral resection of the prostate was performed to relieve bladder outlet obstruction. However, CCA of the prostate was confirmed through pathological examination. A thorough checkup was performed to distinguish it from metastatic clear cell carcinoma from other primary origins. Currently, no consensus for the treatment of CCA of the prostate has been reached. After discussing with the patient, he decided to receive immunotherapy with pembrolizumab. Herein, we reported this rare case of CCA in the prostate.