Background: Nummular headache is a new category of primary headache disorder characterized by consistent location, size, and shape of painful areas. The pathogenesis is uncertain. Bifocal painful areas are rare manifestations but may expand the clinical diversity of nummular headache. Methods: The clinical characteristics of 5 bifocal nummular headache patients were reported and those of 11 patients in previous studies were reviewed. Bifocal nummular headache was classifi ed into two types. Type I was defi ned as a simultaneous activation of two painful areas while type II was defi ned as two painful areas occurring in different times. Results: All 16 patients were female, with mean age of onset and initial presentation of 54.7 years and 58.2 years, respectively. There were seven type I and nine type II patients. The parietal area, especially the tuber parietale, was the leading site of involvement in both types of patients. The shape and size of painful areas were also similar between these two groups. There was an equal frequency of ipsilateral and contralateral painful areas. The pain intensity was similar in both types of patients but was milder in new painful areas than in previous painful areas in type II patients. Conclusions: Bifocal nummular headache suggests a central role of nummular headache but does not debunk the peripheral theory of nummular headache. The accumulated fi ndings in bifocal NH patients do not support a generalization of pain occurrence or a reproduction of local process of epicranial neuralgia at multiple sites in nummular headache.

Objective: This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study. Methods: Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 noncancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders. Results: The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter. Conclusion This population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.

Recombinant tissue plasminogen activator (rt-PA) is the most effective treatment for acute ischemic stroke and the exclusion criteria of rt-PA has been revised to extend its application. However, in Taiwan, National Health Insurance (NHI) did not follow the latest international consensus due to safety concerns. The present study investigated whether extending the application of rt-PA in Taiwan was safe and effective. The medical records from the Shuang Ho hospital stroke registry between August 2009 and December 2016 were retrospectively reviewed. Post rt-PA intracranial hemorrhage (ICH) and modified Rankin Scale (mRS) score at 3-month after stroke were the primary and secondary outcomes, respectively. Differences were analyzed through Fisher’s exact test and Student’s t test. A p-value of <0.05 was considered statistically significant. Overall, there were 243 patients categorized into two groups: NHI exclusion criteria adherence (n = 160) and non-adherence (n = 83). There was no significant difference in the risk of post rt-PA ICH (12.50% in adherence group, 4.82% in non-adherence group, p=0.07). Among the non-adherence group, 10 patients breached the latest international exclusion criteria and none of them experienced post rt-PA ICH. However, among patients with moderately severe stroke, the odds of mRS < 2 at 3-month were significantly lower in non-adherence group. This study demonstrated that extending administration of rt-PA in Taiwan was safe but the functional outcome after moderate stroke was not as favorable as adherence group. Old age, long onset-to-treatment time and less efficacy of lower dose of rt-PA were the possible factors for the difference in outcome.

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.
Animals ; Bile Ducts ; Cell Death ; Cholestasis ; Hepatocytes ; Humans ; Hydrogen ; In Vitro Techniques ; Ligation ; Liver ; Mice ; Nerve Growth Factor ; Phosphotransferases ; Rodentia ; Sirtuin 1

Background: Goslings in several Taiwanese farms experienced gosling feather loss disease (GFL) at 21–35 days and goose broke feather disease (GBF) at 42–60 days. The prevalence ranges from a few birds to 500 cases per field. It is estimated that about 12,000 geese have been infected, the morbidity is 70–80% and the mortality is 20–30%. Objectives: This study aims to investigate the pathogens that cause GFL and GBF. Focus on the study of the correlation between goose circovirus (GoCV) and goose parvovirus (GPV) with the goose feather loss in southern Taiwan. Furthermore, a phylogenetic tree was established to align the differences between southern and northern Taiwan and compare with virus strains from China and Europe. Methods: Samples were collected from animal hospitals. Molecular and microscopy diagnostics were used to examine 92 geese. Specific quantitative polymerase chain reaction (Q-PCR) assays are performed to evaluate GPV and GoCV viral loads and simultaneously evaluated the feather loss conditions in geese with the scoring method. Results: High prevalence of GoCV and GPV infection in geese showing signs of GFL and GBF. Inclusion body was detected in the feather follicles and Lieberkühn crypt epithelial cells. The Q-PCR showed the high correlation between feather loss and viruses during 3rd– 5th week. However, the infection was not detected using the same test in 60 healthy geese. Conclusions Thus, GFL and GBF appear to be significantly closely related to GoCV and GPV. The geese feathers showed increasing recovery after being quarantined and disinfected.

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.