The gestational effect of antenatal corticosteroids on respiratory distress syndrome in very low birth weight infants: A population-based study.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the efficacy of antenatal corticosteroids for preventing very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) from surfactant use at different gestational ages (GA). METHODS: We retrospectively analyzed the VLBW preterm infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2014. Infants at 20-37 weeks' gestation were included, and infants with lethal congenital anomaly, chromosomal anomaly, and congenital infection were excluded. Antenatal corticosteroid courses were classified into two groups (<2 doses or ≧2 doses). The beneficial effect of antenatal corticosteroids on preventing VLBW infants with RDS from surfactant use was evaluated according to gestational ages. RESULTS: Total 12,685 VLBW infants were included. For VLBW infants with gestational age 26-33 weeks, antenatal corticosteroid therapy has significantly protective effect (odds ratio 0.43 [95% CI 0.26 to 0.72] - 0.60 [95% CI 0.48 to 0.75], P < 0.05). The effect was not obvious for VLBW infants with gestational age 34 weeks and more (odds ratio 0.32 [95% CI 0.08 to 1.38], P = 0.127). CONCLUSION: For VLBW infants with RDS at 34 weeks' gestation and more, the beneficial effect of antenatal corticosteroids on preventing surfactant use was not evident. In conclusion, completion of two doses or more of antenatal corticosteroids is of great importance for VLBW infants with RDS at gestational age between 26 and 33 weeks on preventing surfactant use.

Clinical outcomes and safety of remdesivir in hospitalized individuals with COVID-19, with or without severe renal impairment.

BACKGROUND: The use of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal impairment has been approved; however, limited clinical data exist. Accordingly, we aimed to compare outcomes and adverse events associated with remdesivir in hospitalized patients with COVID-19, with and without severe renal impairment. METHODS: Hospitalized patients with COVID-19 undergoing a 5-day remdesivir course at Taipei Veterans General Hospital from April 1 to July 31, 2022, were enrolled. Comparative analysis of outcomes and safety between patients with or without severe renal impairment (estimated glomerular filtration rate of < 30 mL/min per 1.73 m2) were conducted. Prognostic factors associated with 28-day mortality in patients with severe renal impairment were investigated using logistic regression analysis. RESULTS: A total of 671 hospitalized patients, including 132 patients with severe renal impairment, who received a 5-day course of remdesivir were analyzed. The 28-day mortality was higher in patients with severe renal impairment than in patients without severe renal impairment (15.2% vs. 7.8%). The proportion of patients with acute kidney injury (AKI) and deteriorated liver function after completing remdesivir therapy was similar between the patients with and without severe renal impairment, and the recovery rate of AKI was similar in both groups. The sequential organ failure assessment score was an independent factor associated with 28-day mortality in patients with severe renal impairment. CONCLUSIONS: Remdesivir was well-tolerated in hospitalized patients with COVID-19, regardless of renal function. Our findings support the recent recommendation to administer remdesivir in patients with severe renal impairment.

Successful erlotinib rechallenge in an EGFR-mutant metastatic non-small cell lung cancer patient with afatinib-induced drug rash with eosinophilia and systemic symptoms: A case report.

Tyrosine kinase inhibitors (TKIs) are the standard treatment for epidermal growth factor receptor (EGFR)-mutant advanced-stage non-small cell lung cancer (NSCLC). However, TKIs can cause some severe adverse events, which are more prevalent within first-generation EGFR-TKI use than with second-generation inhibitors. Herein, we report a case of a patient with advanced-stage EGFR-mutant NSCLC who developed drug reaction with eosinophilia and systemic symptoms (DRESS) after receiving treatment with afatinib. The patient was successfully rechallenged with erlotinib, without manifestations of skin rash in the following 6 months. Hence, erlotinib may be considered a potential substitute for other EGFR-TKIs following DRESS occurrence.

Obeticholic acid treatment ameliorates the cardiac dysfunction in NASH mice.

BACKGROUND: Suppression of cardiac iinflammasome, which can be inhibited by Farnesoid X receptor (FXR) agonist, can ameliorate cardiac inflammation and fibrosis. Increased cardiac inflammasome decrease the abundance of regulatory T (Treg) cells and exacerbate cardiac dysfunction. Interaction between cardiomyocytes and Treg cells is involved in the development of nonalcoholic steatohepatitis (NASH)-related cardiac dysfunction. AIMS: This study evaluates whether the FXR agonist obeticholic acid (OCA) treatment improves NASH-associated cardiac dysfunction. METHODS: The in vivo and in vitro mechanisms and effects of two weeks of OCA treatment on inflammasome and Treg dysregulation-related cardiac dysfunction in NASH mice (NASH-OCA) at systemic, tissue and cellular levels were investigated. RESULTS: The OCA treatment suppressed the serum and cardiac inflammasome levels, reduced the cardiac infiltrated CD3+ T cells, increased the cardiac Treg-represented anti-inflammatory cytokines (IL-10/IL-10R) and improved cardiac inflammation, fibrosis and function [decreased left ventricle (LV) mass and increased fractional shortening (FS)] in NASH-OCA mice. The percentages of OCA-decreased cardiac fibrosis and OCA-increased FS were positively correlated with the percentage of OCA-increased levels of cardiac FXR and IL-10/IL-10R. In the Treg cells from NASH-OCA mice spleen, in comparison with the Treg cells of the NASH group, higher intracellular FXR but lower inflammasome levels, and more proliferative/active and less apoptotic cells were observed. Incubation of H9c2 cardiomyoblasts with Treg-NASHcm [supernatant of Treg from NASH mice as condition medium (cm)], increased inflammasome levels, decreased the proliferative/active cells, suppressed the intracellular FXR, and downregulated differentiation/contraction marker. The Treg-NASHcm-induced hypocontractility of H9c2 can be attenuated by co-incubation with OCA, and the OCA-related effects were abolished by siIL-10R pretreatment. CONCLUSIONS: Chronic FXR activation with OCA is a potential strategy for activating IL-10/IL-10R signalling, reversing cardiac regulatory T cell dysfunction, and improving inflammasome-mediated NASH-related cardiac dysfunction.

Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats.

Endotoxemia-activated tumor necrosis factor (TNFα)/nuclear factor kappa B (NFκB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ) with pioglitazone can suppress inflammation-related splanchnic and pulmonary dysfunction in cirrhosis. This study explored the mechanism and effects of pioglitazone treatment on the abovementioned renal dysfunction in cirrhotic rats. Cirrhotic ascitic rats were induced with renal dysfunction by bile duct ligation (BDL). Then, 2 weeks of pioglitazone treatment (Pio, PPAR gamma agonist, 12 mg/kg/day, using the azert osmotic pump) was administered from the 6th week after BDL. Additionally, acute lipopolysaccharide (LPS, Escherichia coli 0111:B4; Sigma, 0.1 mg/kg b.w, i.p. dissolved in NaCl 0.9%) was used to induce acute renal dysfunction. Subsequently, various circulating, renal arterial and renal tissue pathogenic markers were measured. Cirrhotic BDL rats are characterized by decreased mean arterial pressure, increased cardiac output and portal venous pressure, reduced renal arterial blood flow (RABF), increased renal vascular resistance (RVR), increased relative renal weight/hydroxyproline, downregulated renal PPARγ expression, upregulated renal inflammatory markers (TNFα, NFκB, IL-6, MCP-1), increased adhesion molecules (VCAM-1 and ICAM-1), increased renal macrophages (M1, CD68), and progressive renal dysfunction (increasing serum and urinary levels of renal injury markers (lipocalin-2 and IL-18)). In particular, acute LPS administration induces acute on chronic renal dysfunction (increasing serum BUN/creatinine, increasing RVR and decreasing RABF) by increased TNFα-NFκB-mediated renal inflammatory markers as well as renal M1 macrophage infiltration. In comparison with the BDL+LPS group, chronic pioglitazone pre-treatment prevented LPS-induced renal pathogenic changes in the BDL-Pio+LPS group. Activation of systemic, renal vessel and renal tissue levels of PPARγ by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNFα/NFκB-mediated acute and chronic renal inflammation in cirrhosis. This study revealed that normalization of renal and renal arterial levels of PPARγ effectively prevented LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.

Prevalence and Genotyping of Chlamydia psittaci from Domestic Waterfowl, Companion Birds, and Wild Birds in Taiwan.

Chlamydia psittaci, the causative agent of avian chlamydiosis, an important zoonotic disease, infects a wide range of birds. Infected birds, whether symptomatic or asymptomatic, intermittently shed the agent through respiratory and intestinal routes. Therefore, it is essential to investigate the epizootiology of C. psittaci in poultry, pet birds, and wild birds. In this study, cloacal or fecal swabs collected from domestic waterfowl, psittacine birds, Columbidae, and wild birds were used to determine the prevalence of C. psittaci in Taiwan between 2014 and 2017. The C. psittaci infection rate was as high as 34.2% among domestic waterfowl farms. The waterfowl isolates clustered into two groups based on ompA phylogeny: one group (G1-like) clustered with the Polish G1 strains; the other group (waterfowl-TW) clustered near, but independently from, the classical ABE genotype cluster. Separately, 3.1% of parrot samples tested positive for C. psittaci belonging to genotype A. C. psittaci isolates of genotype B were detected in 10.1% of racing pigeons and other Columbidae. Wild bird samples from a wildlife refuge had a 2.2% prevalence rate; among these, two atypical C. psittaci genotypes were detected in samples from a Malayan night heron (Gorsachius melanolophus) and a Taiwan barbet (Megalaima nuchalis). Taken together, our results revealed that the risk of C. psittaci transmission from domestic waterfowl and Columbidae birds to humans could be underestimated, given the high prevalence rates in these birds. Furthermore, the free-range rearing system of waterfowl in Taiwan may promote C. psittaci transmission between poultry and wild birds. Pet birds and racing pigeons, which are in close contact with people, are also possible sources for cross-species transmission. Further studies are necessary to elucidate the virulence, biological and genetic characteristics, and modes of transmission of Taiwanese C. psittaci isolates to facilitate the prevention and control of C. psittaci infection.

Acupuncture at distant myofascial trigger spots enhances endogenous opioids in rabbits: a possible mechanism for managing myofascial pain.

BACKGROUND AND AIM: Acupuncture applied at myofascial trigger points (MTrPs) of distant anatomical regions, to reduce pain in a patient's area of primary complaint, is one strategy that is available to manage myofascial pain. However, the endogenous opioid-mediated analgesic mechanism of distant acupuncture associated with pain control is still unclear. This aims of this study were to evaluate the changes in enkephalin and ß-endorphin in serum, spinal cord, dorsal root ganglion (DRG) and muscle induced by acupuncture at distant myofascial trigger spots (MTrSs, similar to human MTrPs) in rabbits, to explore its underlying remote analgesic mechanism. METHODS: Acupuncture at MTrSs of a distant muscle (gastrocnemius) was performed either for one session or five daily sessions in rabbits. The levels of enkephalin and ß-endorphin in proximal muscle (biceps femoris), serum, DRGs and spinal cords (L5-S2) were then determined by immunoassay immediately and 5 days after treatment. RESULTS: Immediately after treatment, acupuncture comprising both one dose and five doses significantly enhanced spinal enkephalin expression and serum ß-endorphin levels (p<0.05). However, only five-dose acupuncture significantly enhanced the ß-endorphin levels in the biceps femoris and DRGs (p<0.05), while 1-dose acupuncture did not (p>0.05). Furthermore, 5 days after treatment, significantly increased levels of spinal enkephalin and serum ß-endorphin persisted in animals that received 5-dose acupuncture (p<0.05). CONCLUSIONS: This study demonstrates that interactions within the endogenous opioid system may be involved in the remote effects of acupuncture treatment and could be a potential analgesic mechanism underlying MTrP pain management.

Remote dose-dependent effects of dry needling at distant myofascial trigger spots of rabbit skeletal muscles on reduction of substance P levels of proximal muscle and spinal cords.

BACKGROUND: Dry needling at distant myofascial trigger points is an effective pain management in patients with myofascial pain. However, the biochemical effects of remote dry needling are not well understood. This study evaluates the remote effects of dry needling with different dosages on the expressions of substance P (SP) in the proximal muscle, spinal dorsal horns of rabbits. METHODS: Male New Zealand rabbits (2.5-3.0 kg) received dry needling at myofascial trigger spots of a gastrocnemius (distant muscle) in one (1D) or five sessions (5D). Bilateral biceps femoris (proximal muscles) and superficial laminaes of L5-S2, T2-T5, and C2-C5 were sampled immediately and 5 days after dry needling to determine the levels of SP using immunohistochemistry and western blot. RESULTS: Immediately after dry needling for 1D and 5D, the expressions of SP were significantly decreased in ipsilateral biceps femoris and bilateral spinal superficial laminaes (P < .05). Five days after dry needling, these reduced immunoactivities of SP were found only in animals receiving 5D dry needling (P < .05). CONCLUSIONS: This remote effect of dry needling involves the reduction of SP levels in proximal muscle and spinal superficial laminaes, which may be closely associated with the control of myofascial pain.