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It is well known that undernourished conditions disturb female reproductive functions in many species, including humans. These alterations are mainly caused by a reduction in gonadotrophin‐releasing hormone (GnRH) secretion from the hypothalamus. Evidence from the literature suggests that some hypothalamic factors play pivotal roles in the coordination of reproductive functions and energy homeostasis in response to environmental cues and internal nutritional status. Generally, anorexigenic/satiety‐related factors, such as leptin, alpha‐melanocyte‐stimulating hormone, and proopiomelanocortin, promote GnRH secretion, whereas orexigenic factors, such as neuropeptide Y, agouti‐related protein, orexin, and ghrelin, attenuate GnRH secretion. Conversely, gonadotrophin‐inhibitory hormone, which exerts anti‐GnRH and gonadotrophic effects, promotes feeding behavior in many species. In addition, the activity of kisspeptin, which is a potent stimulator of GnRH, is reduced by undernourished conditions. Under normal nutritional conditions, these factors are coordinated to maintain both feeding behavior and reproductive functions. However, in undernourished conditions their activity levels are markedly altered to promote feeding behavior and temporarily suppress reproductive functions, in order to prioritize the survival of the individual over that of the species. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) has high recurrence rates. HCC sometimes progresses from early‐stage HCC (Barcelona Clinic Liver Cancer [BCLC] stage 0/A) to advanced‐stage HCC after repeated recurrences and treatments. HCC progression deteriorates quality of life and prognosis. However, the effect of direct‐acting antiviral (DAA)‐induced sustained virologic response (SVR) on HCC progression remains uninvestigated. We conducted a retrospective cohort study of patients with hepatitis C virus‐related HCC with BCLC stage 0/A diagnosed for the first time and treated by curative resection or ablation. Using a time‐varying method, we estimated the risk of tumour progression (defined as progression to BCLC stage B‐D) and liver‐related death and the characteristics of repeated recurrence. Overall, 165 patients were enrolled. Following curative HCC treatment, 72 patients received DAA therapy (DAA‐treated group), whereas 93 did not (untreated group). Approximately 75% of the recurrences were at an early stage and expected to be disease‐free by retreatment. We recorded 56 tumour progressions, of which 60.7% were observed after second recurrence. Multivariate adjusted time‐varying Cox regression analysis showed that the DAA‐induced SVR significantly reduced the risk of tumour progression (hazard ratio [HR] 0.28; p =.001) and liver‐related death (HR 0.12; p <.001). The annual incidence of HCC treatment until tumour progression was 82.8% and 23.9% in the untreated and DAA‐treated groups, respectively (HR 0.30; p <.001). DAA‐induced SVR significantly reduced the risk for tumour progression and liver‐related death and the frequency of HCC treatment following curative treatment for HCC at BCLC stage 0/A. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: The objective of this study was to determine the role of thrombin‐activatable fibrinolysis inhibitor (TAFI) as a candidate biomarker for therapeutic efficacy of sublingual immunotherapy (SLIT) and to identify the role of TAFI in the pathogenesis of allergic rhinitis (AR). Study Design: Retrospective cohort study and laboratory study. Methods: Serum was collected from patients with allergies to Japanese cedar pollen before, during, and after treatment with SLIT. We measured the levels of immunoreactive TAFI, C3a, and C5a in serum by enzyme‐linked immunosorbent assay (ELISA) and assessed their relative impact on a combined symptom‐medication score. We also examined the impact of TAFI on mast cells and fibroblasts in experiments performed in vitro. Results: Serum levels of TAFI increased significantly in response to SLIT. By contrast, serum C3a levels decreased significantly over time; we observed a significant negative correlation between serum levels of TAFI versus C3a and symptom‐medication score. Mast cell degranulation was inhibited in response to TAFI, as it was the expression of both CCL11 and CCL5 in cultured fibroblasts. Conclusions: High serum levels of TAFI may be induced by SLIT. TAFI may play a critical protective role in pathogenesis of AR by inactivating C3a and by inhibiting mast cell degranulation and chemokines expression in fibroblasts. Level of Evidence: 4 Laryngoscope, 131:2413–2420, 2021 [ABSTRACT FROM AUTHOR]

Background and Aim: We assessed direct‐acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV) and a history of injection drug use (IDU) in Japan. Method: This retrospective observational study was based on clinical records. Overall, 804 DAA‐naïve HCV‐infected patients were enrolled, treated with a 12‐week regimen of DAAs, and had available information about a history of IDU. Anti‐HCV efficacy was defined as a sustained viral response 12 weeks post‐treatment (SVR12) only in patients who were assessed after 12 weeks [modified intention‐to‐treat (ITT) analyses]. We compared the antiviral effect between patients with (past‐IDU) and without a history of IDU (non‐IDU). We also evaluated the characteristics of each group, including the overall dropout rate and economic background. Results: Overall, 78 (9.7%) patients had a history of IDU. Compared to the non‐IDU group at baseline, the past‐IDU group consisted of predominantly male and younger patients infected with HCV genotype 2. Overall, 3% (3/78) and 16% (116/726) of the patients had cirrhosis in the past‐IDU and non‐IDU group, respectively. There was a significantly higher rate of welfare recipients in the past‐IDU group. SVR rate was 97% (59/61) in the past‐IDU group and 99% (689/699) in the non‐IDU group. The cumulative rate of dropout from an aftercare program was high in the past‐IDU group (P < 0.01). Conclusions: DAAs had a remarkable anti‐HCV effect in patients with past‐IDU who continued in an aftercare program. It is necessary to understand the characteristics of past‐IDU patients to establish a support system for aftercare programs. [ABSTRACT FROM AUTHOR]

Background: Most patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease (NERD) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD. Methods: We collected nasal polyp tissue from patients with NERD and from patients with aspirin‐tolerant chronic rhinosinusitis with nasal polyps (CRSwNP). Protein profiles were analyzed by 2‐dimensional electrophoresis and identified several proteins, including L‐plastin, as highly expressed. We examined L‐plastin and tissue factor (TF) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L‐plastin in eosinophils, we knocked down L‐plastin expression in Eol‐1 cells by using siRNA transfection. Results: L‐plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRSwNP. Immunofluorescence analysis revealed that L‐plastin was dominantly expressed in eosinophils and L‐plastin and TF were co‐expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L‐plastin in Eol‐1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony‐stimulating factor. Conclusion: Increased expression of L‐plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD. [ABSTRACT FROM AUTHOR]

Background and Aims: It remains unclear whether there is an association between single‐nucleotide polymorphisms (SNPs) and development of hepatocellular carcinoma (HCC) during entecavir (ETV) treatment in nucleos(t)ide analog‐naïve patients with chronic hepatitis B virus infection. We investigated the risk factors for HCC, especially host factors, during ETV treatment. Methods: A total of 127 Japanese patients undergoing ETV treatment were enrolled in this study. Univariate and multivariate analyses for clinical factors, hepatic fibrosis markers, and SNPs associated with HCC development were analyzed. Results: A total of 10 patients developed HCC during the follow‐up period (median duration, 3.3 years). The 3‐, 5‐, and 7‐year cumulative rates of HCC development were 4.8%, 10.6%, and 13.6%, respectively. Liver fibrosis (cirrhosis; P = 0.0005), age (≥ 49 years; P = 0.0048), platelet count (≤ 115 × 10/mm3; P = 0.0007), α‐fetoprotein (≥ 8.0 ng/mL; P = 0.030), type IV collagen (≥ 200 ng/mL; P = 0.043), fibrosis‐4 index (≥ 4.14; P = 0.0006), and human leukocyte antigen (HLA)‐DQA1/DRB1‐SNP (AA genotype; P = 0.0092) were significantly associated with HCC development according to the log‐rank test. In multivariate analysis, AA genotype in the HLA‐DQA1/DRB1 gene (P = 0.013; hazard ratio 4.907; 95% confidence interval 1.407–17.113) and cirrhosis (P = 0.019; hazard ratio 4.789; 95% confidence interval 1.296–17.689) were significantly associated with HCC development. Conclusions: Our findings suggested that patients with AA genotype in the HLA‐DQA1/DRB1 gene or cirrhosis should be carefully followed up as a population potentially at higher risk of HCC during ETV treatment. [ABSTRACT FROM AUTHOR]

Simeprevir (SMV) is a potent, macrocyclic hepatitis C virus (HCV) non-structural 3/4 A protease inhibitor. This prospective study compared the efficacy and safety of SMV in combination with peginterferon α2a + ribavirin (P2aR) and with peginterferon α2b + ribavirin (P2bR) in Japanese patients with HCV genotype 1b infection. Methods Hepatitis C virus genotype 1b patients were randomly assigned to receive SMV (100 mg QD) with P2aR for 12 weeks, then P2aR alone for 12 or 36 weeks; or SMV (100 mg QD) with P2bR for 12 weeks, then P2bR alone for 12 or 36 weeks. The primary endpoint was a sustained virologic response 24 weeks after completing treatment (SVR24). Results In total, 151 patients were randomly assigned to the P2aR (n = 76) or P2bR group (n = 75). Six patients dropped out. Sustained virologic response 24 weeks after completing treatment was achieved in 55 (75.3%) of 73 P2aR patients and 55 (76.4%) of 72 P2bR patients. There was no difference in the rate of SVR24 between the two groups (P = 0.88). No differences in the proportion of patients who became HCV RNA-negative were detected between the P2aR and P2bR groups. The two groups had comparable numbers of adverse events, which led to the discontinuation of treatment in 9.6% and 8.3% of participants in the P2aR and P2bR groups, respectively. Conclusion Peginterferon α2a or α2b in combination with SMV + ribavirin therapy showed identical antiviral effects in patients with chronic hepatitis C. Also, the incidence of adverse events was identical for both regimens. [ABSTRACT FROM AUTHOR]

There is no consensus on the choice of either unilateral or bilateral drainage in stent placement for patients with unresectable hilar biliary obstruction. The aim of the present study was to clarify which drainage method is superior. We retrospectively reviewed 82 patients with hilar biliary obstruction who underwent metallic stenting. These patients were divided into a unilateral drainage group (Uni group) and a bilateral drainage group (Bi group). There was no significant difference between the groups in median survival time, median stent patency period, and median complication-free survival time. The most frequent complication was stent obstruction, followed by cholangitis. Liver abscess was found at a higher frequency in the Bi group (17.6%) than in the Uni group (1.5%) ( P = 0.0266). There was no significant difference between the groups in the occurrence of two or more complications ( P = 0.247), life-threatening severe complications ( P = 0.0577), and stent obstruction by sludge ( P = 0.0912). When compared with bilateral biliary drainage, unilateral biliary drainage is associated with a lower incidence of liver abscess as well as a comparable outcome of stent patency time and complication-free survival. We therefore propose that hilar biliary obstruction can be treated first by unilateral drainage with a metallic stent and by bilateral drainage only in patients who develop cholangitis in the contralateral biliary tree. [ABSTRACT FROM AUTHOR]

Pemphigus and pemphigoid are different types of autoimmune bullous disease and can occur in the same patient. We report a female patient with this condition. At first, we diagnosed her with bullous pemphigoid, and we treated her with tetracycline, niacinamide and a topical steroid. Tense bullas disappeared shortly after that, but crusted erythemas mainly on her head and trunk persisted. We examined BP180 and desmoglein 1 enzyme-linked immunosorbent assays, and also histological features, which showed coexistence of bullous pemphigoid and pemphigus foliaceus concurrently. Therefore, we tried prednisolone, which could control both conditions. This case showed that tetracycline and niacinamide could control bullous pemphigoid, but could not control pemphigus foliaceus, and that prednisolone was effective for both conditions. [ABSTRACT FROM AUTHOR]

Short tandem repeat studies are powerful tools for parentage analysis and for identification of missing persons, victims of murder, and victims of mass fatalities when reference samples are unavailable. The primer in the Identifiler® kit failed to amplify an allele at the D19S433 locus, producing a silent (“null”) allele. The causal mutation is a base change (G>A) 32 nucleotides downstream from the 3′ end of the AAGG repeats. The silent alleles are problematical in parentage analysis because when transmitted, they can cause a parent–child inconsistency that is unrelated to Mendelian genetics. The inconsistency is sometimes termed an “apparent opposite homozygosity” and it produces false evidence of nonparentage. Alternative primers were designed to amplify the D19S433 locus alleles and they detect the silent allele. Frequencies of the (no longer) silent allele were determined to be 0.0114 in 176 people from Shizuoka (Honshu) and 0.0128 in 156 people from Okinawa. [ABSTRACT FROM AUTHOR]

A 53-year-old woman was referred to our hospital with the main symptoms of productive cough, fever and exertional dyspnoea. Chest X-ray revealed enlargement of the left hilar shadow and cavitary infiltration in the right upper lobe. 99mTechnetium-macroaggregated albumin (99mTc-MAA) perfusion scintigram showed complete hypoperfusion through the entire right lung. A pulmonary angiogram revealed stenotic lesions in the right and left main pulmonary arteries. Right cardiac catheterization showed an elevated right ventricular systolic pressure. There was no evidence of systemic arterial lesions nor vasculitis. The patient was positive for myeloperoxidase (MPO)antineutrophil cytoplasmic autoantibodies (ANCA) (168 EU). The Mycobacterium avium complex sputum culture was positive. The pulmonary stenotic lesions were surgically resected. The resected pulmonary arterial lesions were pathologically diagnosed as non-specific vasculitis. The cavitary lesion disappeared 6 months after the surgery. Two years after the surgery, although the MPO-ANCA level had decreased to 12 EU, stenosis of the pulmonary arteries reappeared. It is suggested that the patient became positive for MPO-ANCA in association with the Mycobacterium avium complex infection, and that the presence of MPO-ANCA may not be related to the development of pulmonary stenosis of the main pulmonary arteries. [ABSTRACT FROM AUTHOR]

A 47-year-old woman was admitted to hospital with severe Legionella pneumonia. The respiratory symptoms improved dramatically and the X-rays revealed a decrease in the diffuse chest infiltrates after treatment with erythromycin and rifampicin. However, chest CT scans showed that the reticulonodular opacities persisted for several weeks after the onset of pneumonia. Two months after admission, the chest X-rays showed the progression of small nodules in both lungs and there was increasing respiratory distress. A diagnosis of miliary tuberculosis was confirmed. The present case should alert physicians to this potentially confusing combination of respiratory pathogens. [ABSTRACT FROM AUTHOR]

Studies allele frequencies of 15 loci in a population sample from Japan, using a short tandem polymerase chain reaction amplication kit from Applied BioSystems. DNA extraction from blood samples; Allelic frequencies.