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Ventricular septal perforation is a rare complication of pacemaker implantation. Here, we describe the case of a 69-year-old man with complete atrioventricular block and heart failure. The right ventricular pacemaker was implanted with a long pre-shaped delivery sheath. A new systolic murmur appeared after the procedure. Transthoracic echocardiography revealed a ventricular septal perforation, with a Qp/Qs of 1.09, which was a small shunt rate and required no intervention. The persistent ventricular septal perforation was observed, and the shunt rate remained at 8-month follow-up. Ventricular septal lead perforation (VSP) is a rare complication of pacemaker implantation. Although iatrogenic VSP generally close spontaneously without adverse clinical outcomes, clinicians should pay attention to the possibility of its persistence. [ABSTRACT FROM AUTHOR]

Biologics or molecularly targeted drugs are often highly effective for the treatment of allergic diseases and other immunologic disorders, and they are relatively safe for short-term use as compared with conventional approaches such as the systemic use of corticosteroids. A number of studies published in 2021 consistently demonstrated their effectiveness and also revealed unanticipated findings. Among them, clinical trials for asthma and chronic obstructive pulmonary disease using biologics targeting thymic stromal lymphopoietin, IL-33, and IL-33 receptor demonstrated that these type 2 alarmin cytokines are also involved in non–type 2, noneosinophilic inflammation. Randomized controlled trials reporting the efficacies of 2 small-molecule oral drugs targeting Janus kinase-1 had a substantial impact on the management of atopic dermatitis. These drugs demonstrated superiority over dupilumab, which has previously demonstrated efficacy and is in wide use in clinical practice. As a concern, biologics are generally costly, and it should be noted that racial/ethnic minority populations may be less likely to receive biologics in the real world. Here, we have reviewed recent clinical trials and related topics dealing with the effects of biologics on allergic and immunologic diseases; in addition, we discuss how our understanding of the pathophysiology of these disorders has progressed. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are key regulators of IgE-mediated allergic inflammation. Cell-derived extracellular vesicles (EVs) contain bioactive compounds such as microRNAs. EVs can transfer signals to recipient cells, thus using a novel mechanism of cell-to-cell communication. However, whether MC-derived EVs are involved in FcεRI-mediated allergic inflammation is unclear. We sought to investigate the effect of EVs derived from FcεRI-aggregated human MCs on the function of human group 2 innate lymphoid cells (ILC2s). Human cultured MCs were sensitized with and without IgE for 1 hour and then incubated with anti-IgE antibody, IL-33, or medium alone for 24 hours. EVs in the MC supernatant were isolated by using ExoQuick-TC. Coculture of ILC2s with EVs derived from the FcεRI-aggregated MCs significantly enhanced IL-5 production and sustained upregulation of IL-5 mRNA expression in IL-33–stimulated ILC2s, but IL-13 production and IL-13 mRNA expression were unchanged. miR103a-3p expression was upregulated in IL-33–stimulated ILC2s that had been cocultured with EVs derived from anti-IgE antibody–stimulated MCs. Transduction of an miR103a-3p mimic to ILC2s significantly enhanced IL-5 production by IL-33–stimulated ILC2s. miR103a-3p promoted demethylation of an arginine residue of GATA3 by downregulating protein arginine methyltransferase 5 (PRMT5) mRNA. Reduction of protein arginine methyltransferase 5 expression in ILC2s by using a small interfering RNA technique resulted in upregulation of IL-5 production by IL-33–stimulated ILC2s. Furthermore, the level of miR103a-3p expression was significantly higher in EVs from sera of patients with atopic dermatitis than in EVs from nonatopic healthy control subjects. Eosinophilic allergic inflammation may be exacerbated owing to ILC2 activation by MC-derived miR103a-3p. [ABSTRACT FROM AUTHOR]

• Verification of reference beam profiles (RBPs) for preconfigured Halcyon. • Comparison of RBPs and accurate measured beam profiles (MBPs) with novel rigid board. • Measurements of beam profiles with water tank on the board bridged Halcyon bore. • Supplied RBPs can be used as golden beam data due to good agreement with MBPs. • This work should be useful for new Halcyon users. This study performed the accurate measurements of beam profiles with a new rigid board, which was consistent with the supplied reference beam profiles (RBPs) for clinical Halcyon model. Percentage depth doses (PDDs), lateral and diagonal dose profiles were measured and compared with RBPs. A water tank was set on the rigid board bridged Halcyon bore without sagging and source-to-surface distance was 90.0 cm. Field sizes were from 2.0 to 28.0 cm squares and depths of lateral and diagonal dose profiles were 1.3, 5.0, 10.0, and 20.0 cm. For the PDD, the depth of maximum dose (d max), PDD value at depth of 10.0 cm (PDD 10), and absolute dose difference (DD) between RBP and measured beam profiles (MBP) were evaluated. For lateral and diagonal dose profiles, DDs for the whole and divided areas (central, shoulder, and extended areas) defined by third derivative, and distance-to-agreement (DTA) in the penumbra area were evaluated. For PDDs, the differences of d max and PDD 10 and DD beyond the d max were within 1.0 mm, 0.3%, and 1.0%, respectively. For lateral and diagonal dose profiles, the DDs reached approximately 5.0% in the whole area because of penumbra area, while the DDs in the central, shoulder, and extended areas were within 1.0%, 2.0%, and 1.0%, respectively. The DTAs in the penumbra area were within 0.8 mm. The supplied RBPs can be used clinically owing to the good agreement with the accurate MBPs with rigid board. [ABSTRACT FROM AUTHOR]

Elevated blood pressure (BP) level is one of the most consistently identified risk factors for silent brain disease. BP values obtained at the proximal segment of the aorta (central BP) are more directly involved than brachial BP in the pathogenesis of cardiovascular disease. However, the association between central BP and silent cerebrovascular disease has not been clearly established. Participants in the CABL (Cardiovascular Abnormalities and Brain Lesions) study (n=993; mean age, 71.7±9.3 years; 37.9% men) underwent 2-dimensional echocardiography, arterial wave reflection analysis for determination of central BPs, and brain magnetic resonance imaging. Central BPs were calculated from the radial pulse waveform. Subclinical silent cerebrovascular disease was defined as silent brain infarction and white matter hyperintensity volume. Both brachial (P=0.014) and central pulse pressure (P=0.026) were independently associated with silent brain infarctions after adjustment for clinical variables, but not adjusting for each other. None of the brachial BP values was associated with upper quartile of white matter hyperintensity volume in multivariable analysis. Both central systolic BP (P<0.001) and central pulse pressure (P<0.001) were significantly associated with upper quartile of white matter hyperintensity volume in multivariable analysis, even after adjustment for brachial BP. In a predominantly older population-based cohort, both brachial and central pulse pressure were independently associated with silent brain infarction. However, higher central systolic BP and central pulse pressure, but not brachial BP, were significantly associated with white matter hyperintensity volume. [ABSTRACT FROM AUTHOR]

To evaluate the success of a patient-specific intensity modulated radiation therapy (IMRT) quality assurance (QA) practice for prostate cancer patients across multiple institutions using a questionnaire survey. The IMRT QA practice involves different methods of dose distribution verification and analysis at different institutions. Two full-arc volumetric modulated arc therapy (VMAT) plan and 7 fixed-gantry IMRT plan with DMLC were used for patient specific QA across 22 institutions. The same computed tomography image and structure set were used for all plans. Each institution recalculated the dose distribution with fixed monitor units and without any modification. Single-point dose measurement with a cylindrical ionization chamber and dose distribution verification with a multi-detector or radiochromic film were performed, according to the QA process at each institution. Twenty-two institutions performed the patient-specific IMRT QA verifications. With a single-point dose measurement at the isocenter, the average difference between the calculated and measured doses was 0.5 ± 1.9%. For the comparison of dose distributions, 18 institutions used a two or three-dimensional array detector, while the others used Gafchromic film. In the γ test with dose difference/distance-to-agreement criteria of 3%−3 mm and 2%−2 mm with a 30% dose threshold, the median gamma pass rates were 99.3% (range: 41.7%–100.0%) and 96.4% (range: 29.4%–100.0%), respectively. This survey was an informative trial to understand the verification status of patient-specific IMRT QA measurements for prostate cancer. In most institutions, the point dose measurement and dose distribution differences met the desired criteria. [ABSTRACT FROM AUTHOR]

This study compared volumetric-modulated arc therapy (VMAT) plans for head and neck cancers with and without an external body contour extended technique (EBCT). Dose calculation algorisms for VMAT have limitations in the buildup region. Three VMAT plans were enrolled, with one case having a metal artifact from an artificial tooth. The proper dose was calculated using Eclipse version 11.0. The body contours were extended 2 cm outward from the skin surface in three-dimensional space, and the dose was recalculated with an anisotropic analytical algorithm (AAA) and Acuros XB (AXB). Monitor units (MUs) were set, and the dose distributions in the planning target volume (PTV), clinical target volume, and organ at risk (OAR) and conformity index (CI) with and without an EBCT were compared. The influence of a metal artifact outside of the thermoplastic head mask was also compared. The coverage of PTV by the 95% dose line near the patient's skin was increased drastically by using an EBCT. Plan renormalization had a negligible impact on MUs and doses delivered to OARs. CI of PTV with a 6-MV photon beam was closer to 1 than that with a 10-MV photon beam when both AAA and AXB were used in all cases. Metal artifacts outside the head mask had no effect on dose distribution. An EBCT is needed to estimate the proper dose at object volumes near the patient's skin and can improve the accuracy of the calculated dose at target volumes. [ABSTRACT FROM AUTHOR]

• We developed a new real time variable shape rubber containing tungsten (STR). • The STR is a rubber material with no cross-linked polymerization. • We explored temperature features and shielding ability with electron beam and γ-ray. • Changing shape in real time at 60 °C and maintains its shape at body temperatures. • STR gives adequate shielding against megavoltage electron beams and 192Ir γ-rays. To clarify the physical characteristics of a newly developed real time variable shape rubber containing tungsten (STR) with changes in heat and estimate its shielding abilities against electron beams and γ-rays from 192Ir. Dynamic mechanical analysis for the STR (density = 7.3 g/cm3) was conducted at a frequency of 1.0 Hz in the temperature range of −60 °C to 60 °C. We evaluated tanδ, defined as the ratio (E″/E′) between the storage modulus (E′) and loss modulus (E″). The transmission rates were measured against 6- and 12-MeV electron beams and the percentage depth dose and lateral dose profile were compared with low-melting alloy (LMA). For the shielding rate of 192Ir against γ-rays, measurement data and Monte Carlo simulation data were obtained with STR thickness ranging from 1.0 mm to 16.0 mm. At 36 °C, the tanδ value was 0.520, while at 60 °C, this value was 1.016. For 6- and 12-MeV electron beams, the transmission rates decreased with increasing STR thickness and reached plateaus at approximately 1.0% and 4.0% with STR thickness of >7.0 and >12.0 mm, respectively. The dose distributions were almost equal to those for LMA. Against γ-rays, the thickness of STR that obtained a 50% attenuation rate for 192Ir was 5.804 mm. The Monte Carlo calculation results were 2.6% higher on average than the measurement results. The STR can be changed shape in real time at 60 °C and maintains its shape at body temperatures. It has adequate shielding abilities against megavoltage electron beams and γ-rays from 192Ir. [ABSTRACT FROM AUTHOR]

• Irradiation time can be increased for targets misaligned with the gantry isocenter in TomoTherapy. • Planning target volume location offsets of ≥5 cm increased the irradiation time. • Phantom offset did not affect the irradiation time. The influence of the offset distance from treatment target to gantry isocenter (GIC) on the dosimetric parameter and irradiation time was investigated using TomoTherapy The reference position was defined as the centers of both the I'mRT phantom and planning target volume (PTV) with a spherical of 4 cm diameter aligned with the GIC. The dose calculations were performed in two offset methods with 2 and 12 Gy/fr, Method 1. The PTV was moved from 0.0 to 12.5 cm along the RL direction and −5.0 to 5.0 cm along the AP direction (PTV offset), Method 2. The phantom was moved from 0.0 to −7.5 cm along the RL direction and −5.0 to 5.0 cm along the AP direction (Phantom offset). The maximum, minimum and mean doses, homogeneity index, conformity index, irradiation time, and monitor unit were compared. The irradiation times increased with increasing PTV offset. The increases in the irradiation time were 54.4% and 40.8% at PTV offsets of 12.5 cm along the RL direction for 2 and 12 Gy/fr, while the increases were 20.1% and 15.0% at a PTV offset of 5.0 cm along the AP direction. An increased irradiation time was not observed for the phantom offset. The offset didn't affect the other parameters. The PTV location offset of ≥5 cm from the GIC along the RL and AP axes increased the irradiation time; therefore, the PTV should be aligned with the GIC as much as possible to reduce the irradiation time on TomoTherapy. [ABSTRACT FROM AUTHOR]

Summary Background & aims Although parenteral nutrition (PN) is often used after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there is controversy regarding PN management, for instance in the use of fat emulsion and glucose control (GC). To clarify these issues, we conducted a multi-center prospective study with intensive GC, randomizing the use of fat emulsion after allo-HSCT using a myeloablative conditioning regimen. Methods The primary endpoint was the cumulative incidence of documented infectious disease, namely bacterial and fungal infection, at day 100 after allo-HSCT. Between August 2007 and March 2012, we enrolled 81 patients at 5 centers. Excluding 5 ineligible patients, 76 patients received the protocol treatment. The target fasting glucose level was 80–110 mg/dL. Results The median follow-up of surviving patients was 1796 days. The cumulative incidences of documented infectious disease at day 100 were 16% (95% confidence interval [CI] 6–29%) in the no-fat group and 19% (95% CI 8–32%) in the fat group, indicating no significant difference. The mean glucose level at 28 days after allo-HSCT was 107 mg/dL in the no-fat group and 111 mg/dL in the fat group. Grade 3 hyperglycemia (>250 mg/dL) and grade 3 hypoglycemia (<40 mg/dL) occurred in 4 patients each (5.3%). Overall survival and non-relapse mortality rates at 4 years were 75% and 11% in the no-fat group and 69% and 8% in the fat group, respectively. Conclusions Irrespective of the use of fat emulsion, the long-term clinical outcomes of the enrolled patients were favorable under intensive GC. To further clarify the benefits of GC after allo-HSCT, a prospective study randomizing the level of GC is warranted. [ABSTRACT FROM AUTHOR]

Papain (cysteine protease), subtilisin (Protin SD-AY10, serine protease), and bacillolysin (Protin SD-NY10, metallo protease) increased the specific volume of gluten-free rice breads by 19-63% compared to untreated bread. In contrast, Newlase F (aspartyl protease) did not expand the volume of the rice bread. In a rheological analysis, the viscoelastic properties of the gluten-free rice batters also depended on the protease categories. Principal component analysis (PCA) analysis suggested that the storage and loss moduli (G′ and G″, respectively) at 35 °C, and the maximum values of G′ and G″, were important factors in the volume expansion. Judging from the PCA of the viscoelastic parameters of the rice batters, papain and Protin SD-AY10 improved the viscoelasticity for gluten-free rice bread making, and Protin SD-NY effectively expanded the gluten-free rice bread. The rheological properties differed between Protin SD-NY and the other protease treatments. [ABSTRACT FROM AUTHOR]

Allergic diseases were long considered to be complex multifactorial disorders. However, recent findings indicate that severe allergic inflammation can be caused by monogenic immune defects. We sought to clarify the molecular pathogenesis of a patient with early-onset multiple allergic diseases, a high serum IgE level, hypereosinophilia, treatment-resistant severe atopic dermatitis with increased dermal collagen fiber deposition, and eosinophilic gastrointestinal disorder with numerous polypoid nodules. A missense variant in STAT6 was identified, and its function was examined using peripheral blood, transfected HEK293 cells, lymphoblastoid cell lines, and knock-in mice with the corresponding mutation. Whole-exome sequencing identified a de novo heterozygous missense variant in signal transducer and activator of transcription 6 (STAT6) (p.Asp419Asn). Luciferase reporter assay revealed that the transcriptional activity of this STAT6 mutant was upregulated even without IL-4 stimulation. Phosphorylation of STAT6 was not observed in either the patient's T H 2 cells or lymphoblastoid cell lines without stimulation, whereas it was induced more strongly in both by IL-4 stimulation compared with healthy controls. STAT6 protein was present in the nuclear fraction of the lymphoblastoid cell lines of the patient even in the absence of IL-4 stimulation. The patient's gastric mucosa showed upregulation of STAT6-, fibrosis-, and germinal center formation–related molecules. Some of the knock-in mice with the corresponding mutation spontaneously developed dermatitis with skin thickening and eosinophil infiltration. Moreover, serum IgE levels and mRNA expression of type 2 cytokines were increased in the knock-in mice—with or without development of spontaneous dermatitis—compared with the wild-type mice. A novel STAT6 gain-of-function variant is a potential cause of primary atopic disorders. [Display omitted] [ABSTRACT FROM AUTHOR]