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Postherpetic neuralgia (PHN) is a notorious neuropathic pain featuring persistent profound mechanical hyperalgesia with significant negative impact on patients' life quality. CDDO can regulate inflammatory response and programmed cell death. Its derivative also protects neurons from damages by modulating microglia activities. As a consequence of central and peripheral sensitization, applying neural blocks may benefit to minimize the risk of PHN. This study aimed to explore whether CDDO could generate analgesic action in a PHN‐rats' model. The behavioural test was determined by calibrated forceps testing. The number of apoptotic neurons and degree of glial cell reaction were assessed by immunofluorescence assay. Activation of PKC‐δ and the phosphorylation of Akt were measured by western blots. CDDO improved PHN by decreasing TRPV1‐positive nociceptive neurons, the apoptotic neurons, and reversed glial cell reaction in adult rats. It also suppressed the enhanced PKC‐δ and p‐Akt signalling in the sciatic nerve, dorsal root ganglia (DRG) and spinal dorsal horn. Our research is the promising report demonstrating the analgesic and neuroprotective action of CDDO in a PHN‐rat's model by regulating central and peripheral sensitization targeting TRPV1, PKC‐δ and p‐Akt. It also is the first study to elucidate the role of oligodendrocyte in PHN. [ABSTRACT FROM AUTHOR]

Background: Treating postherpetic neuralgia (PHN), which is characterized with a long‐lasting lancinating mechanical allodynia or hyperalgesia, is a big challenge as it is hard to achieve complete resolution. A synthetic triterpenoid, CDDO (2‐cyano‐3,12‐dioxoolean‐1,9‐dien‐28‐oic acid) can exert pleiotropic effects including anti‐inflammation and neuroprotective activities. Nevertheless, the antinociceptive effect of CDDO and its derivatives remains unknown. Resiniferatoxin (RTX) is easily feasible, and an RTX‐treated rodent model can mimic the PHN‐like symptoms. Therefore, RTX‐treated rats were used to serve as a PHN rats' model in the study to elucidate whether a synthetic triterpenoid, CDDO, can improve mechanical allodynia in RTX‐treated rats. Methods: The antinociceptive effects of CDDO were assessed by behavioral tests, western blotting, and immunohistochemistry. Paw withdrawal mechanical threshold was determined using calibrated forceps. Results: Administration of RTX led to mechanical allodynia, neuronal cell death, and glial cell activation in the spinal cord of RTX‐treated rats. A synthetic triterpenoid, CDDO, blocked RTX‐induced mechanical allodynia, rescued neuronal cell death, and inhibited glial cell activation in the spinal cord of RTX‐treated rats. Conclusions: Our study provides a novel result that a synthetic triterpenoid, CDDO, can interfere neuronal cell death and glial cell activation in the spinal cord of RTX‐treated rats. Hence, CDDO is an alternative therapeutic choice for PHN. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic bone‐resorbing disease that easily causes subsequent risk of fracture. Hence, the substantial physical burden of osteoporosis makes it an important public health issue. Seborrheic dermatitis (SD) is a chronic, recurrent, inflammatory skin disease. Despite the advances in medication for treating osteoporosis, identifying undiagnosed osteoporosis patients is still challenging. Since osteoporosis and SD share a similar pathobiology, e.g. inflammation and hormonal imbalance, we aimed to investigate whether the existence of SD increases osteoporosis risk by using the Taiwan National Health Insurance Research Database. A total of 7831 patients aged 18–50 years with SD and a control group of 31 324 patients without SD matched by age, gender, Charlson Comorbidity Index, and index date at a ratio of 1:4 during 1996–2010 were recruited in the study. To measure the cumulative incidence and compare the hazard ratios of osteoporosis between each group, the Kaplan–Meier method and Cox proportional hazard regression models were utilized. It was found that 0.98% of SD patients had osteoporosis. Compared to the non‐SD group, the SD group had a 5.95‐fold higher osteoporosis risk after adjustment for variables. The impact of SD on osteoporosis risk was largest in the female and young age groups. In addition, the presence of hyperlipidemia, hyperthyroidism, and epilepsy synergistically increased osteoporosis incidence in the SD group. This first large cohort study demonstrated an association between SD and osteoporosis. Since the effect on bone health in SD patients with concomitant diseases is largest in early life, diet or lifestyle recommendations as well as regular bone examinations are advised during follow‐up of SD. [ABSTRACT FROM AUTHOR]

Background: Fibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated by physical activity. Both keloids and migraines can cause physical exhaustion and discomfort in patients; they have similar pathophysiological pathways, that is, the transforming growth factor-β1 gene and neurogenic inflammation.Objective: To investigate subsequent development of migraines in patients with keloids. Methods Data were retrieved from the Taiwan National Health Insurance Research Database. The keloids group included patients aged 20 years and older with a recent diagnosis of keloids(n=9864). The non-keloids group included patients without keloids matched for gender and age at 1-4 ratio (n=39 456). Migraine risk between groups was measured by Cox proportional hazards regression models. Incidence rates and hazard ratios were calculated.Results: During the study period, 103 keloids patients and 323 non-keloids patients developed migraines. The keloids patients had a 2.29-fold greater risk of developing migraines compared with the non-keloids group after adjustment for covariates (1.81 vs 0.55 per 1000 person-years, respectively). In the keloids group, female or patients younger than 50 years were prone to developing migraines.Conclusion: The higher tendency to develop migraines in the keloids group in comparison with the non-keloids group suggests that keloids could be a predisposing risk factor for migraine development in adults. Keloids patients who complain of headaches should be examined for migraines. [ABSTRACT FROM AUTHOR]

Byline: Ying-Yi. Lu, Chun-Ching. Lu, Chieh-Shan. Wu, Chieh-Hsin. Wu Angiokeratoma corporis diffusum is the cutaneous hallmark of several rare inherited lysosomal diseases associated with specific enzyme deficiencies in the metabolism [...]

Background: Osteoporosis and stroke are major health problems that have potentially overlapping pathophysiological mechanisms. The aim of this study was to estimate osteoporosis risk in Taiwan patientswho had a stroke.Method: This study retrieved data contained in the Taiwan National Health Insurance Research Database for a population-based sample of consecutive patients either hospitalised for stroke or treated for stroke on an outpatient basis. A total of 7550 newly diagnosed patientswho had a stroke were enrolled during 1996-2010. Osteoporosis risk in these patients was then compared with a matched group of patients who had not had a stroke randomly selected from the database at a ratio of 1:4 (n=30 200). The relationship between stroke history and osteoporosis risk was estimated with Cox proportional hazard regression models.Results: During the follow-up period, osteoporosis developed in 1537 patients who had a stroke and in 5830 patients who had not had a stroke. The incidence of osteoporosis for cohorts with and without stroke was 32.97 and 14.28 per 1000 person-years, respectively. After controlling for covariates, the overall risk of osteoporosis was 1.82-fold higher in the stroke group than in the non-stroke group. The relative osteoporosis risk contributed by stroke had apparently greater impact among male gender and younger age groups.Conclusion: History of stroke is a risk factor for osteoporosis in Taiwan. Much attention to stroke-targeted treatment modalities might minimise adverse outcomes of osteoporosis. [ABSTRACT FROM AUTHOR]

Resiniferatoxin is an ultrapotent capsaicin analog that mediates nociceptive processing; treatment with resiniferatoxin can cause an inflammatory response and, ultimately, neuropathic pain. Hepatoma-derived growth factor, a growth factor related to normal development, is associated with neurotransmitters surrounding neurons and glial cells. Therefore, the study aims to investigate how blocking hepatoma-derived growth factor affects the inflammatory response in neuropathic pain. Serum hepatoma-derived growth factor protein expression was measured via ELISA. Resiniferatoxin was administrated intraperitoneally to induce neuropathic pain in 36 male Sprague-Dawley rats which were divided into three groups (resiniferatoxin+recombinant hepatoma-derived growth factor antibody group, resiniferatoxin group, and control group) (n = 12 /group). The mechanical threshold response was tested with calibration forceps. Cell apoptosis was measured by TUNEL assay. Immunofluorescence staining was performed to detect apoptosis of neuron cells and proliferation of astrocytes in the spinal cord dorsal horn. RT-PCR technique and western blot were used to measure detect inflammatory factors and protein expressions. Serum hepatoma-derived growth factor protein expression was higher in the patients with sciatica compared to controls. In resiniferatoxin-group rats, protein expression of hepatoma-derived growth factor was higher than controls. Blocking hepatoma-derived growth factor improved the mechanical threshold response in rats. In dorsal root ganglion, blocking hepatoma-derived growth factor inhibited inflammatory cytokines. In the spinal cord dorsal horn, blocking hepatoma-derived growth factor inhibited proliferation of astrocyte, apoptosis of neuron cells, and attenuated expressions of pain-associated proteins. The experiment showed that blocking hepatoma-derived growth factor can prevent neuropathic pain and may be a useful alternative to conventional analgesics. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide, and its treatment is potentially a heavy economic burden. Suicide is another global public health problem and the second leading cause of death in young adults. Patients with TBI are known to have higher than normal rates of non-fatal deliberate self-harm, suicide and all-cause mortality. The aim of this study was to explore the association between TBI and suicide risk in a Chinese cohort.Method: This study analysed data contained in the Taiwan National Health Insurance Research Database for 17 504 subjects with TBI and for 70 016 subjects without TBI matched for age and gender at a ratio of 1 to 4. Cox proportional hazard regression analysis was used to estimate subsequent suicide attempts in the TBI group. Probability of attempted suicide was determined by Kaplan-Meier method.Results: The overall risk of suicide attempts was 2.23 times higher in the TBI group compared with the non-TBI group (0.98 vs 0.29 per 1000 person-years, respectively) after adjustment for covariates. Regardless of gender, age or comorbidity, the TBI group tended to have more suicide attempts, and the risk attempted suicide increased with the severity of TBI. Depression and alcohol attributed disease also increased the risk of attempted suicide in the TBI group.Conclusion: Suicide is preventable if risk factors are recognised. Hence, TBI patients require special attention to minimise their risk of attempted suicide. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death, morbidity and disability worldwide. Infection is a common complication in the acute phase after stroke. Herpes zoster is a common viral disease, in which the most debilitating complication is post-herpetic neuralgia, which can have a very large negative impact on quality of life. The aim of this study was to investigate whether stroke increases the risk of herpes zoster. Methods: This cohort study compared patients who had herpes zoster with and without a first incident of stroke. The Taiwan National Health Insurance Research Database was utilized to identify 20,551 stroke patients and 20,551 controls matched for age, gender, age categories and Charlson Comorbidity Index (CCI) score categories at a one-to-one ratio. Cox proportional-hazards regression models were employed to estimate herpes zoster risk in the stroke group relative to general population. Results: Compared to the control group, the stroke group had a greater risk for herpes zoster, especially within 1 year after stroke (adjust HR = 25.27). Both hemorrhagic stroke and ischemic stroke were significantly associated with herpes zoster (hemorrhagic type (IRR = 2.31, 95% CI, 1.67–3.20); ischemic type (IRR = 2.51, 95% CI 2.09–3.02)). However, the hemorrhagic stroke patients had a higher risk of herpes zoster ophthalmicus (IRR = 12.46, 95% CI 4.00–38.76) whereas the ischemic stroke patients had a higher risk of post-herpetic neuralgia (IRR = 2.24, 95% CI 1.56–3.20). Conclusion: Physicians should know about that adults with stroke have a higher than normal risk of herpes zoster. Thus, physicians must be acquainted with proper antiviral therapy and pain control to bring down the morbidity that ensues from herpes zoster. Use of herpes zoster vaccine may be considered in stroke patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. [ABSTRACT FROM AUTHOR]

Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and migraine are both important public health problems and may have overlapping pathophysiological mechanisms. The aim of this study was to use a Taiwanese population-based dataset to assess migraine risk in osteoporosis patients. Methods: The Taiwan National Health Insurance Research Database was used to analyse data for 40,672 patients aged ≥20 years who had been diagnosed with osteoporosis during 1996-2010. An additional 40,672 age-matched patients without osteoporosis were randomly selected as the non-osteoporosis group. The relationship between osteoporosis and migraine risk was estimated using Cox proportional hazard regression models. Results: During the follow-up period, 1110 patients with osteoporosis and 750 patients without osteoporosis developed migraine. After controlling for covariates, the overall incidence of migraine was 1.37-fold higher in the osteoporosis group than in the non-osteoporosis group (3.72 vs. 1.24 per 1000 person-years, respectively). Migraine risk factors included high Charlson Comorbidity Index score, female gender, hypertension, depression, asthma, allergic rhinitis, obesity, and tobacco use disorder. Conclusions: Our results indicate that patients with a history of osteoporosis had a higher risk of migraine. [ABSTRACT FROM AUTHOR]

The aims of this study were to investigate the risk of hip fracture and contributing factors in patients with erectile dysfunction(ED). This population-based study was performed using the Taiwan National Health Insurance Research Database. The analysis included4636 patients aged ≥ 40 years who had been diagnosed with ED (International Classification of Diseases, Ninth Revision, Clinical Modification codes 302.72, 607.84) during 1996–2010. The control group included 18,544 randomly selected age-matched patients without ED (1:4 ratio). The association between ED and hip fracture risk was estimated using a Cox proportional hazard regression model. During the follow-up period, 59 (1.27%) patients in the ED group and 140 (0.75%) patients in the non-ED group developed hip fracture. After adjusting for covariates, the overall incidence of hip fracture was 3.74-times higher in the ED group than in the non-ED group (2.03 vs. 0.50 per 1000 person-years, respectively). The difference in the overall incidence of hip fracture was largest during the 3-year follow-up period (hazard ratio = 7.85; 95% confidence interval = 2.94–20.96; P <0.0001). To the best of our knowledge, this nationwide population-based study is the first to investigate the relationship between ED and subsequent hip fracture in an Asian population. The results showed that ED patients had a higher risk of developing hip fracture. Patients with ED, particularly those aged 40–59 years, should undergo bone mineral density examinations as early as possible and should take measures to reduce the risk of falls. [ABSTRACT FROM AUTHOR]

A novel degradable crosslinker, N, N′-bis(acryloyl) cystamine (BACy), was synthesized with cystamine dihydrochloride (Cy) and acryloyl chloride. Then three series of degradable thermosensitive hydrogels with different crosslinker contents were prepared from N-isopropyl acrylamide (NIPAAm), BACy (Bx-series) or N, N′-methylene-bis-acrylamide (NMBA)(Nx-series) or equimolar BACy and NMBA (BNx-series) as crosslinker, and diethoxyacetophenone (DEAP) as photoinitiator under UV-irradiation polymerization. The effect of crosslinker content on the properties of the hydrogels such as swelling behavior and mechanical properties was investigated. At the same time, their degradabilities were investigated by dissolving them into different concentrations of cysteine solution. The results show that the swelling ratios for the Bx-series hydrogels are lower than those for the Nx-series hydrogels. But, after degradation in the cysteine solution, the swelling ratios for the Bx-series hydrogels were greater than those for the Nx-series hydrogels. When the crosslinker content was increased, all values of shear stress (τ), shear modulus (G), and effective crosslinking density (ρX) increased. But, the ρX values for the reduced Bx series and BNx series hydrogels were lower than those for original hydrogels. Results also showed that the ρX values for the Nx series hydrogel were not affected by cysteine. The disulfide bonds of BACy in these novel hydrogels were decomposed (reduced) in the cysteine solution and converted into thiol group. These thiol groups could be used to absorb some metal ions such as silver ion. Hence, the absorption of silver ion for the hydrogel with thiol group was also investigated in this research. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury involves divergent alterations within dorsal root ganglia (DRG) neurons sensitized by persistent inflammation. Thymic stromal lymphopoietin (TSLP) production is crucial in the development of chronic inflammatory responses. Herein, we investigate the changes of TSLP expression in rats' DRG neurons between injured and uninjured sides in the same rat. Linalyl acetate (LA) was served as a TSLP inhibitor and given intraperitoneally. Rats were assigned to be group of chronic constriction injury (CCI) of the sciatic nerve and the group of CCI of the sciatic nerve administrated with LA. Over 14 days, the rats were measured for paw withdrawal thresholds. DRGs were collected to assess morphological changes via immunofluorescence study. After receiving CCI, the rats rapidly developed mechanical hyperalgesia. TSLP expression at DRG, on the ipsilateral injured side, was consistent with changes in pain behaviors. TSLP appeared in nerve fibers with both small diameters and large diameters. Additionally, TSLP was expressed mostly in transient receptor potential vanilloid-1 (TRPV1)-positive nociceptive neurons. Administration with LA can attenuate the pain behaviors and expression of TSLP in DRG neurons, and in apoptotic neurons at the injured side, but not in the contra-lateral uninjured side. Overall, these results imply that altered expressions of TSLP in nociceptive DRG neurons contributed to mechanical hyperalgesia in a CCI rat model. [ABSTRACT FROM AUTHOR]

A subarachnoid hemorrhage (SAH), leading to severe disability and high fatality in survivors, is a devastating disease. Neuro-inflammation, a critical mechanism of cerebral vasospasm and brain injury from SAH, is tightly related to prognoses. Interestingly, studies indicate that 2-[(pyridine-2-ylmethyl)-amino]-phenol (2-PMAP) crosses the blood–brain barrier easily. Here, we investigated whether the vasodilatory and neuroprotective roles of 2-PMAP were observed in SAH rats. Rats were assigned to three groups: sham, SAH and SAH+2-PMAP. SAHs were induced by a cisterna magna injection. In the SAH+2-PMAP group, 5 mg/kg 2-PMAP was injected into the subarachnoid space before SAH induction. The administration of 2-PMAP markedly ameliorated cerebral vasospasm and decreased endothelial apoptosis 48 h after SAH. Meanwhile, 2-PMAP decreased the severity of neurological impairments and neuronal apoptosis after SAH. Furthermore, 2-PMAP decreased the activation of microglia and astrocytes, expressions of TLR-4 and p-NF-κB, inflammatory markers (TNF-α, IL-1β and IL-6) and reactive oxygen species. This study is the first to confirm that 2-PMAP has vasodilatory and neuroprotective effects in a rat model of SAH. Taken together, the experimental results indicate that 2-PMAP treatment attenuates neuro-inflammation, oxidative stress and cerebral vasospasm, in addition to ameliorating neurological deficits, and that these attenuating and ameliorating effects are conferred through the TLR-4/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Primary intestinal lymphangiectasia is a rare disease of children, which is characterized by chronic diarrhea and complicated with malnutrition, including fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age. She presented initially with chronic diarrhea at 4 months of age. Generalized edema with hypoalbuminemia frequently occurred despite regular albumin supplements. Multiple vitamins initially were not supplied regularly. Episodes of tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low serum 25-hydroxy vitamin D concentration (< 12.48 mmol/L, the detection limit)] and secondary hyperparathyroidism were confirmed via blood testing. Vitamin D supplementation for 3 months improved her bone density, secondary hyperparathyroidism and frequent tetany. Vitamin D status should be monitored in patients with intestinal lymphangiectasia. [Copyright &y& Elsevier]

Thymic stromal lymphopoietin (TSLP) is a well-known cytokine for T helper 2 inflammatory responses. A nerve injury activates the neuroinflammation cascade and neuron–glia interaction in dorsal root ganglions (DRG)s, leading to neuropathic pain. Therefore, this study was to investigate the role of TSLP after nerve injury. Male Sprague-Dawley rats were divided as an experimental group with chronic constriction injury (CCI) to the sciatic nerve and a control group. The mechanical pain threshold response was determined by calibration forceps. After assessment of mechanical allodynia, the ipsilateral spinal cord, DRG, sciatic nerve and skin were harvested. Immunofluorescence staining was performed to identify cell types with various markers. Western blot analyses were performed to evaluate protein expressions. Mechanical allodynia developed after CCI and persisted for the next 14 days. Astrocyte reactions occurred and continued until day 14, too. After CCI, DRG and the sciatic nerve also had significantly increased expressions of TSLP/TSLP-R/STAT5. The TSLPR was localized to sensory neuronal endings innervating the skin. This study is the first to demonstrate that the TSLP complex and the STAT5 pathway in nerve are potential therapeutic targets because of their roles in pain regulation after nerve injury. [ABSTRACT FROM AUTHOR]

A keloid is a fibroproliferative skin tumor. Proliferating keloid fibroblasts (KFs) demand active metabolic utilization. The contributing roles of glycolysis and glucose metabolism in keloid fibroproliferation remain unclear. This study aims to determine the regulation of glycolysis and glucose metabolism by glucose transporter-1 (GLUT-1), an essential protein to initiate cellular glucose uptake, in keloids and in KFs. Tissues of keloids and healthy skin were explanted for KFs and normal fibroblasts (NFs), respectively. GLUT-1 expression was measured by immunofluorescence, RT-PCR, and immunoblotting. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with or without WZB117, a GLUT-1 inhibitor. Reactive oxygen species (ROS) were assayed by MitoSOX immunostaining. The result showed that glycolysis (ECAR) was enhanced in KFs, whereas OCR was not. GLUT-1 expression was selectively increased in KFs. Consistently, GLUT-1 expression was increased in keloid tissue. Treatment with WZB117 abolished the enhanced ECAR, including glycolysis and glycolytic capacity, in KFs. ROS levels were increased in KFs compared to those in NFs. GLUT-1 inhibition suppressed not only the ROS levels but also the cell proliferation in KFs. In summary, the GLUT-1-dependent glycolysis and ROS production mediated fibroblast proliferation in keloids. GLUT1 might be a potential target for metabolic reprogramming to treat keloids. [ABSTRACT FROM AUTHOR]

Abstract: Gallbladder perforation is an extremely rare condition in infants. We present a premature infant who had congestive heart failure and renal failure owing to complex congenital heart disease and developed gallbladder perforation at 60 days of age. The patient showed neither signs of peritonitis nor impaired liver function; however, we found bile drainage from the peritoneal dialysis tube. Emergent laparotomy revealed a 3-mm perforation with surrounding tissue necrosis over the gallbladder neck. Cholecystectomy was performed after patent common bile duct was demonstrated using intraoperative cholangiography. No stones were noted in the gallbladder. Further histologic examinations of the perforation site showed ischemic changes. There were no biliary complications after surgery. Nevertheless, the patient died of multiple organ failure at 120 days old. [Copyright &y& Elsevier]

Although the expression of p53 and epidermal growth factor receptor (EGFR) is associated with therapeutic resistance and patient outcomes in many malignancies, the relationship in astrocytomas is unclear. This study aims to correlate p53 and EGFR expression in brain astrocytomas with overall patient survival. Eighty-two patients with astrocytomas were enrolled in the study. Semi-quantitative p53 and EGFR immunohistochemical staining was measured in tumor specimens. The mean follow-up after astrocytoma surgery was 18.46 months. The overall survival rate was 83%. Survival was reduced in EGFR-positive patients compared with survival in EGFR-negative patients (p < 0.05). However, no significant differences in survival were detected between patients with high and low p53 expression. In patients with low p53 expression, positive EGFR staining was associated with significantly worse survival compared with patients with negative EGFR staining (log-rank test: p < 0.001). Survival rates in positive and negative EGFR groups with high p53 protein expression were similar (log-rank test: p = 0.919). The IC50 of an EGFR inhibitor was higher in GBM cells with high p53 protein expression compared with the IC50 in cells with low p53 expression. Combined EGFR and p53 expression may have prognostic significance in astrocytomas.

Background: Fibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated by physical activity. Both keloids and migraines can cause physical exhaustion and discomfort in patients; they have similar pathophysiological pathways, that is, the transforming growth factor-β1 gene and neurogenic inflammation., Objective: To investigate subsequent development of migraines in patients with keloids. Methods Data were retrieved from the Taiwan National Health Insurance Research Database. The keloids group included patients aged 20 years and older with a recent diagnosis of keloids(n=9864). The non-keloids group included patients without keloids matched for gender and age at 1-4 ratio (n=39 456). Migraine risk between groups was measured by Cox proportional hazards regression models. Incidence rates and hazard ratios were calculated., Results: During the study period, 103 keloids patients and 323 non-keloids patients developed migraines. The keloids patients had a 2.29-fold greater risk of developing migraines compared with the non-keloids group after adjustment for covariates (1.81 vs 0.55 per 1000 person-years, respectively). In the keloids group, female or patients younger than 50 years were prone to developing migraines., Conclusion: The higher tendency to develop migraines in the keloids group in comparison with the non-keloids group suggests that keloids could be a predisposing risk factor for migraine development in adults. Keloids patients who complain of headaches should be examined for migraines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoporosis and stroke are major health problems that have potentially overlapping pathophysiological mechanisms. The aim of this study was to estimate osteoporosis risk in Taiwan patientswho had a stroke., Method: This study retrieved data contained in the Taiwan National Health Insurance Research Database for a population-based sample of consecutive patients either hospitalised for stroke or treated for stroke on an outpatient basis. A total of 7550 newly diagnosed patientswho had a stroke were enrolled during 1996-2010. Osteoporosis risk in these patients was then compared with a matched group of patients who had not had a stroke randomly selected from the database at a ratio of 1:4 (n=30 200). The relationship between stroke history and osteoporosis risk was estimated with Cox proportional hazard regression models., Results: During the follow-up period, osteoporosis developed in 1537 patients who had a stroke and in 5830 patients who had not had a stroke. The incidence of osteoporosis for cohorts with and without stroke was 32.97 and 14.28 per 1000 person-years, respectively. After controlling for covariates, the overall risk of osteoporosis was 1.82-fold higher in the stroke group than in the non-stroke group. The relative osteoporosis risk contributed by stroke had apparently greater impact among male gender and younger age groups., Conclusion: History of stroke is a risk factor for osteoporosis in Taiwan. Much attention to stroke-targeted treatment modalities might minimise adverse outcomes of osteoporosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide, and its treatment is potentially a heavy economic burden. Suicide is another global public health problem and the second leading cause of death in young adults. Patients with TBI are known to have higher than normal rates of non-fatal deliberate self-harm, suicide and all-cause mortality. The aim of this study was to explore the association between TBI and suicide risk in a Chinese cohort., Method: This study analysed data contained in the Taiwan National Health Insurance Research Database for 17 504 subjects with TBI and for 70 016 subjects without TBI matched for age and gender at a ratio of 1 to 4. Cox proportional hazard regression analysis was used to estimate subsequent suicide attempts in the TBI group. Probability of attempted suicide was determined by Kaplan-Meier method., Results: The overall risk of suicide attempts was 2.23 times higher in the TBI group compared with the non-TBI group (0.98 vs 0.29 per 1000 person-years, respectively) after adjustment for covariates. Regardless of gender, age or comorbidity, the TBI group tended to have more suicide attempts, and the risk attempted suicide increased with the severity of TBI. Depression and alcohol attributed disease also increased the risk of attempted suicide in the TBI group., Conclusion: Suicide is preventable if risk factors are recognised. Hence, TBI patients require special attention to minimise their risk of attempted suicide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Traumatic brain injury is now a major contributor to the global healthcare burden. Migraine is another debilitating disease with a global health impact. While most researchers agree that traumatic brain injury is a risk factor for migraine, whether migraine is a risk factor for traumatic brain injury still remains under debate. We therefore aimed to investigate whether migraine was a risk factor for developing traumatic brain injury., Study Design: Retrospective population-based cohort study., Setting: Data for people who had been diagnosed with migraine were retrieved from Taiwan's National Health Insurance Research Database., Participants: We identified 7267 patients with newly diagnosed migraine during 1996-2010. The migraineurs to non-migraineurs ratio was set at 1:4 to enhance the power of statistical tests., Primary and Secondary Outcome Measures: We used multivariate Cox proportional hazard regression models to assess the effects of migraines on the risk of traumatic brain injury after adjusting for potential confounders., Results: The overall traumatic brain injury risk was 1.78 times greater in the migraine group compared with the non-migraine group after controlling for covariates. Additionally, patients with previous diagnoses of alcohol-attributed disease, mental disorders and diabetes mellitus had a significantly higher traumatic brain injury risk compared with those with no history of these diagnoses., Conclusions: This study of a population-based database indicated that migraine is a traumatic brain injury risk factor. Greater attention to migraine-targeted treatment modalities may reduce traumatic brain injury-related morbidity and mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The pathogenesis of keloid is largely unknown. Because keloid and atopic dermatitis have overlapping pathophysiological mechanisms, we aimed to evaluate keloid risk in patients with atopic dermatitis., Study Design: Population-based retrospective cohort study., Setting: The Taiwan National Health Insurance Research Database was used to analyse data for people who had been diagnosed with atopic dermatitis., Participants: We identified 8371 patients with newly diagnosed atopic dermatitis during 1996-2010. An additional 33 484 controls without atopic dermatitis were randomly identified and frequency matched at a one-to-four ratio., Primary and Secondary Outcome Measure: The association between atopic dermatitis and keloid risk was estimated using Cox proportional hazard regression models., Results: After adjustment for covariates, the atopic dermatitis patients have a 3.19-fold greater risk of developing keloid compared with the non-atopic dermatitis group (3.19vs1.07 per 1000 person-years, respectively). During the study period, 163 patients with atopic dermatitis and 532 patients without atopic dermatitis developed keloid. Notably, keloid risk increased with severity of atopic dermatitis, particularly in patients with moderate to severe atopic dermatitis., Conclusions: Our results indicate that patients with atopic dermatitis had a higher than normal risk of developing keloid and suggest that atopic dermatitis may be an independent risk factor for keloid., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)