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.

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.

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.

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.

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.

Clocking tinnitus: An audiology symptom of migraine.

OBJECTIVES: In contrast to previous concept that tinnitus is confined to an otologic disorder, current evidence supports it as a phantom sensory phenomenon of vestibulocochlear damage with cortical reorganization. It is a common problem worldwide, but the treatment response is always unsatisfactory. PATIENTS AND METHODS: In this study, we report 10 patients who described their staccato tinnitus as simulating the ticking sound of a pendulum or quartz clock (or termed clocking tinnitus). The tinnitus characteristics, laboratory tests, and treatment response were recorded. RESULTS: Clocking tinnitus was unilateral in three patients, bilateral in one patient, and at midline in another six patients. It usually subsided within 15 min. Neither patient experienced vertigo, hemifacial spasm, focal neurological deficit or otic disorder in association with tinnitus. Pre-existing migraine was present in seven patients. During tinnitus attack, a few migraine symptoms concurrently occurred in six patients. Pure-tone audiometry showed symmetric sloping pattern of hearing impairment in half patients whereas brainstem auditory evoked potentials revealed a prolonged wave I-III latency in 30% of patients. The p300 and electroencephalogram were normal in all of them. Neuroimaging study did not disclose structural change. All patients responded poorly to conventional treatments but favorably to flunarizine or topiramate. CONCLUSION: Clocking tinnitus may be an audiology manifestation of migraine in some individuals. Antimigraine treatment can be considered in this specific group of staccato tinnitus. Audiogenic classification of tinnitus may provide diagnostic and treatment clues in tinnitus patients.

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.

Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice.

Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.

Pornography headache.

The headache associated with intercourse or masturbatory activity is a well-recognized clinical entity but pornography headache is barely mentioned. We report a young man who suffered preorgasmic headache pertaining only to pornography of specific erotic contents but not to other sexual or nonsexual act. An antecedent activation of sexual arousal and vasoconstriction during pain were found. Finally, oral indomethacin favorably prevented the pain. Therefore, pornography headache is a distinguished headache disorder distinct from other sexual-related headache disorders. Sexual arousal-mediated cerebrovascular dysregulation consequence to visuoneural uncoupling in response to erotic stimulus is proposed. Pornography headache may be underestimated in population as pain-killer overuse may mask the actual incidence in real world.

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.

Vitamin D receptor-binding site variants affect prostate cancer progression.

Vitamin D is an important modulator of cellular proliferation through the vitamin D receptor (VDR) that binds to DNA in the regulatory sequences of target genes. We hypothesized that single nucleotide polymorphisms (SNPs) in VDR-binding sites might affect target gene expression and influence the progression of prostate cancer. Using a genome-wide prediction database, 62 SNPs in VDR-binding sites were selected for genotyping in 515 prostate cancer patients and the findings were replicated in an independent cohort of 411 patients. Prognostic significance on prostate cancer progression was assessed by Kaplan-Meier analysis and the Cox regression model. According to multivariate analyses adjusted for known predictors, HFE rs9393682 was found to be associated with disease progression for localized prostate cancer, and TUSC3 rs1378033 was associated with progression for advanced prostate cancer in both cohorts. Vitamin D treatment inhibited HFE mRNA expression, and down-regulation of HFE by transfecting small interfering RNA suppressed PC-3 human prostate cancer cell proliferation and wound healing ability. In contrast, vitamin D treatment induced TUSC3 expression, and silencing TUSC3 promoted prostate cancer cell growth and migration. Further analysis of an independent microarray dataset confirmed that low TUSC3 expression correlated with poor patient prognosis. Our results warrant further studies using larger cohorts. This study identifies common variants in VDR-binding sites as prognostic markers of prostate cancer progression and HFE and TUSC3 as plausible susceptibility genes.

Expression of redox sensing factor Nrf2 in lung macrophages and type II pneumocytes as a prognostic factor in pneumothorax recurrence.

BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence. METHODS: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. RESULTS: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively). CONCLUSIONS: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidence-of-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

Pulmonary Blastoma in Children: Report of a Rare Case and Review of the Literature.

Pulmonary blastoma is a rare malignant lung tumor with aggressive behavior and dismal prognosis. It is extremely rare in children aged <18 years, and little is known about its genetic alteration and pathogenesis. Although surgical resection and adjuvant chemotherapy or radiotherapy have been applied in several cases, no standard treatment guidelines with sufficient evidence have been established. In this article, we report a case of a large pulmonary blastoma in a 7-year-old girl whose initial presentation was progressive dyspnea and productive cough. We subsequently present a review on cases involving young patients as well as genetic analysis data available in the literature.

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.

Cheiro-pedal syndrome: A revisit of etiology, localization and outcome.

OBJECTIVE: Cheiro-pedal syndrome (CPS) is an incomplete sensory disorder confined to hand and foot and is generally considered a benign entity. However, knowledge comes from case report or case series only. The aim of this study is to clarify the etiology, localization and outcome of CPS. PATIENT AND METHOD: A total of 21 CPS patients from our database and another 9 patients from literature were reviewed. CPS was classified into 4 types, namely unilateral and ipsilateral (Type I), bilateral (Type II), incomplete bilateral (Type III), and crossed (Type IV). RESULTS: They were 20 men and 10 women; including 20 Type I patients, 9 Type II patients, 1 Type III patients, and 0 Type IV patient. Vascular disorders, non-vascular cervical disorder and polyneuropathy were the responsible causes in 18 patients, 7 patients, and 2 patients, respectively. Etiology was unknown in another 3 patients. Lesions were located at brain parenchyma in 16 patients, and cervical cord above C5 level in 9 patients. Disable motoroparesis occurred between 4days to 2 months in two-third of deteriorated patients. In three patients, their lesions were detected only on recurrence or exacerbation of CPS 4 months to 2 years later. Recovery, residual deficit and deterioration ensued in 44%, 28% and 28% patients, respectively. A 33.3% of brain involvement patients and 100.0% of spinal involvement patients terminated to residual deficit or deterioration. The sensitivity and specificity of prediction for deterioration was 77.8% and 100%, respectively, by type II or III CPS. CONCLUSION: CPS is actually not a benign neurological disorder but a sensory alarm sign. A thorough examination of brain parenchyma and cervical spinal cord is urgent for identifying any treatable or preventable pathological lesions to reduce harmful consequence, especially in case of type II or III CPS.

Crossed cheiro-oral syndrome: A warning sign for medullary involvement and neurological deterioration.

Crossed cheiro-oral syndrome (CCOS) is characterized by crossed sensory disturbance confined to the unilateral perioral area and contralateral hand/finger(s). Although a few classical crossed sensory syndromes accurately predict brainstem or spinal involvement, the clinical significance of CCOS remains unclear. In this study, we analyzed the etiology, localization and outcome of CCOS patients. The results showed that ischemic stroke is the exclusive cause of CCOS. The location of responsible stroke is pertinent to the middle or upper level of the lateral medulla oblongata medial to the lateral sulcus. The vascular supply is from the vertebral artery or the posterior inferior cerebellar artery. Half of the CCOS patients progressed to Wallenberg's syndrome and complicated with disabled daily living. However, no patient died during the follow-up period. A larger size and dorsal extension of the infarction correlated with neurological deterioration. Therefore, CCOS is an independent clinical sign of medullary involvement. It strongly predicts involvement at the lateral medulla oblongata, especially the ischemic stroke, and neurological deterioration. A rapid evaluation of the infarction location and vascular status is suggested in cases of CCOS.

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.

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.

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.