Effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation: A nationwide study in Japan based on the National Clinical Database.

Aim: Possible negative effects of the COVID-19 pandemic on short-term postoperative outcomes for colorectal perforation in Japan were examined in this study. Methods: The National Clinical Database (NCD) is a large-scale database including more than 95% of surgical cases in Japan. We analyzed 13 107 cases of colorectal perforation from 2019 to 2021. National data were analyzed, and subgroup analyses were conducted for subjects in prefectures with high infection levels (HILs) and metropolitan areas (Tokyo Met. and Osaka Pref.). Postoperative 30-day mortality, surgical mortality, and postoperative complications (Clavien-Dindo grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: In the NCD, postoperative 30-day mortality occurred in 1371 subjects (10.5%), surgical mortality in 1805 (13.8%), and postoperative complications in 3950 (30.1%). Significantly higher SMRs were found for 30-day mortality in November 2020 (14.6%, 1.39 [95% CI: 1.04-1.83]) and February 2021 (14.6%, 1.48 [95% CI: 1.10-1.96]), and for postoperative complications in June 2020 (37.3%, 1.28 [95% CI: 1.08-1.52]) and November 2020 (36.4%, 1.21 [95% CI: 1.01-1.44]). The SMRs for surgical mortality were not significantly high in any month. In prefectures with HILs and large metropolitan areas, there were few months with significantly higher SMRs. Conclusions: The COVID-19 pandemic had limited negative effects on postoperative outcomes in patients with colorectal perforation. These findings suggest that the emergency system for colorectal perforation in Japan was generally maintained during the pandemic.

Age-specific nasal epithelial responses to SARS-CoV-2 infection.

Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.

High-power and high-efficiency operation of 1.3 µm-wavelength InP-based photonic-crystal surface-emitting lasers with metal reflector.

We demonstrate high-output-power and high-efficiency operation of 1.3-µm-wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). By introducing a metal reflector and adjusting the phase of the reflected light via optimization of the thickness of the p-InP cladding layer, we successfully achieve an output power of approximately 400 mW with the slope efficiency of 0.4 W/A and the wall-plug efficiency of 20% under CW conditions. In addition, this PCSEL exhibits a narrow circular beam with a divergence angle below 1.6° even at high output powers under CW conditions at temperatures from 15°C to 50°C. We have also demonstrated an output power of over 12 W under pulsed conditions at room temperature.

Polypharmacy of Older Surgical Patients With Extremity Fractures.

Introduction: Fractures are often caused by falls in older people. Among various causes of falls, polypharmacy is known to be a risk of falls. Furthermore, potentially inappropriate medicines (PIMs), which interact with polypharmacy, include the drugs involved in falls. Here, we primarily aimed to investigate the prescribed drugs in older surgical patients with extremity fractures to determine the frequency of polypharmacy and identify PIMs. The second aim was to clarify the characterization of prescribed drugs of older patients with hip fracture. Materials and Methods: We retrospectively collected the following clinical data of consecutive patients aged ≥65 years who underwent surgery for extremity fractures at our hospital between April 2019 and March 2021. A total of 19 categories were considered as PIMs. The Poisson regression models were used to examine the association between the number of prescribed drugs and hip fracture prevalence. Results: A total of 590 patients were reviewed. Our data showed that 55% of older patients with extremity fractures took ≥6 prescription drugs. The frequency of prescription of hypnotics, antithrombotic drugs, diuretics, and non-steroidal anti-inflammatory drugs was comparatively high among the 19 categories of PIMs. Multivariable analysis revealed that polypharmacy was significantly associated with hip fractures. Among PIMs, antithrombotic drugs and diuretics were significantly associated with the prevalence of hip fractures. Finally, we found a significant positive association between the prevalence of hip fracture and the number of drug categories of PIMs among older patients with extremity fractures. Conclusions: The present study clarified the characterization of the prescribed drugs in older surgical patients with extremity fractures. Special attention should be paid to hip fractures of older patients with polypharmacy or prescribed with many drugs categories of PIMs, particularly antithrombotic drugs and diuretics.

Critical swallowing functions contributing to dysphagia in patients with recurrent laryngeal nerve paralysis after esophagectomy.

BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy can cause aspiration because of incomplete glottis closure, leading to pneumonia. However, patients with RLNP often have preserved swallowing function. This study investigated factors that determine swallowing function in patients with RLNP. METHODS: Patients with esophageal cancer who underwent esophagectomy and cervical esophagogastric anastomosis were enrolled between 2017 and 2020. Videofluoroscopic examination of swallowing study (VFSS) and acoustic voice analysis were performed on patients with suspected dysphagia including RLNP. Dysphagia in VFSS was defined as score ≥ 3 of the 8-point penetration-aspiration scale VFSS and acoustic analysis results related to dysphagia were compared between patients with and without RLNP. RESULTS: Among 312 patients who underwent esophagectomy, 74 developed RLNP. The incidence of late-onset pneumonia was significantly higher in the RLNP group than in the non-RLNP (18.9 vs. 8.0%, P = .008). Detailed swallowing function was assessed by VFSS in 84 patients, and patients with RLNP and dysphagia showed significantly shorter maximum diagonal hyoid bone elevation (10.62 vs. 16.75 mm; P = .003), which was a specific finding not seen in patients without RLNP. For acoustic voice analysis, the degree of hoarseness was not closely related to dysphagia. The length of oral intake rehabilitation for patients with and without RLNP was comparable if they did not present with dysphagia (8.5 vs. 9.0 days). CONCLUSIONS: Impaired hyoid bone elevation is a specific dysphagia factor in patients with RLNP, suggesting compensatory epiglottis inversion by hyoid bone elevation is important for incomplete glottis closure caused by RLNP.

Refund: a defense of luck egalitarian policy in healthcare.

Luck egalitarianism assigns a central role to personal responsibility in egalitarian justice. In the context of healthcare, luck egalitarianism is the view that the distribution of medical and healthcare resources-or common resources in general-should respond to the (im)prudence of individuals. Recently, Joar Björk, Gert Helgesson, and Niklas Juth have argued that it is impractical to use luck egalitarianism as a normative framework in healthcare because it has no reasonable way of dealing with the imprudent. In response to their argument, this paper first suggests that the epistemic problems of applying luck egalitarianism to the healthcare context raised by Björk et al. can be circumvented by using the exemption system as a policy application of luck egalitarian healthcare justice. This paper then shows that an ex ante policy, a tax system with refunds, can reasonably be adopted as a luck egalitarian institutional design of healthcare policy. We argue that the proposed conception of luck egalitarianism can deal with the problem of differential option luck. Finally, we show that the threshold problem for the definition of imprudence does not refute the proposed ex ante policy.

A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

BACKGROUND: A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. PATIENTS AND METHODS: Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. RESULTS: Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. CONCLUSION: APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Early human lung immune cell development and its role in epithelial cell fate.

Studies of human lung development have focused on epithelial and mesenchymal cell types and function, but much less is known about the developing lung immune cells, even though the airways are a major site of mucosal immunity after birth. An unanswered question is whether tissue-resident immune cells play a role in shaping the tissue as it develops in utero. Here, we profiled human embryonic and fetal lung immune cells using scRNA-seq, smFISH, and immunohistochemistry. At the embryonic stage, we observed an early wave of innate immune cells, including innate lymphoid cells, natural killer cells, myeloid cells, and lineage progenitors. By the canalicular stage, we detected naive T lymphocytes expressing high levels of cytotoxicity genes and the presence of mature B lymphocytes, including B-1 cells. Our analysis suggests that fetal lungs provide a niche for full B cell maturation. Given the presence and diversity of immune cells during development, we also investigated their possible effect on epithelial maturation. We found that IL-1ß drives epithelial progenitor exit from self-renewal and differentiation to basal cells in vitro. In vivo, IL-1ß-producing myeloid cells were found throughout the lung and adjacent to epithelial tips, suggesting that immune cells may direct human lung epithelial development.

Early prediction of cytokine release syndrome by measuring phosphate and magnesium levels following chimeric antigen receptor T cell therapy.

Introduction: Cytokine release syndrome (CRS) is a life-threatening side effect of chimeric antigen receptor T (CAR-T) cell therapy. This study investigated whether serum inorganic phosphate (IP) and magnesium (Mg) levels are predictive markers of CRS development. Methods: This single-center retrospective cohort study enrolled 16 consecutive patients with diffuse large B-cell lymphoma who had received CAR-T cell therapy. Logistic regression models with generalized estimating equations were used to evaluate whether changes in IP and Mg levels from their baseline values were associated with the development of CRS within 48 hours. Results: Decreased IP and Mg levels from baseline (per 10% change) were associated with an increased CRS incidence (adjusted odds ratio 2.18 [95% confidence interval (CI), 1.31-3.62], 3.18 [95% CI, 1.57-6.44], respectively). Conclusions: Changes in IP and Mg concentrations within 48 hours may be useful predictive markers of CRS onset.

Usefulness of High-resolution Computed Tomography for Macrolide Therapy of Idiopathic Bronchiectasis.

Background: High-resolution computed tomography (HRCT) correlates with clinical symptoms, respiratory function, and quality of life in bronchiectasis. Objective: We aimed to investigate the relationship between macrolide and acute exacerbation (AE) in idiopathic bronchiectasis classified by the Bronchiectasis Radiologically Indexed CT Score (BRICS). Methods: We retrospectively reviewed the medical records of patients diagnosed with idiopathic bronchiectasis between April 2014 and December 2020 at a single hospital. Overall, 115 patients with idiopathic bronchiectasis were selected and divided into three groups, according to the BRICS. Each group was divided into subgroups with and without macrolide therapy, and the number of patients with AE in each group was retrospectively compared. Results: About 45, 48, and 22 patients were included in the mild, moderate, and severe groups, respectively. In the mild group, the subgroup with macrolide therapy had significantly fewer patients with single AE than those without macrolide ( P = 0.029). There was no significant difference in the moderate and severe groups ( P = 1.00 and 0.64, respectively). In the multiple AE, the subgroup with macrolide therapy had significantly fewer patients than those without macrolide therapy in the mild, moderate, and severe groups ( P = 0.024, 0.029, and 0.026, respectively). Conclusion: HRCT severity assessment might be useful in predicting treatment efficacy in patients with idiopathic bronchiectasis without previous AEs. Further large-scale clinical trials are required on the usefulness of HRCT in the future.

200-W short-pulse operation of photonic-crystal lasers based on simultaneous absorptive and radiative Q-switching.

Short-pulse high-peak-power lasers are crucial laser sources for various applications such as non-thermal ultrafine material processing and eye-safe high-resolution remote sensing. Realizing such operation in a single semiconductor laser chip without amplifiers or external resonators is expected to contribute to the development of compact, affordable laser sources for such applications. In this paper, we demonstrate short-pulse high-peak-power photonic-crystal surface-emitting lasers based on simultaneous absorptive and radiative Q-switching. The proposed device induces an instantaneous and simultaneous decrease in both absorptive and out-of-plane radiation losses due to saturable absorption and self-evolution of the photonic band, respectively, which results in drastic Q-switching operation of the device. Based on this concept, we experimentally demonstrate short-pulse generation with 200-W-class peak power and a pulse width of < 30 ps. In addition, via pulse compression with dispersion compensation, we achieve an even higher peak power of ∼300 W with a shorter pulse width of ∼10 ps.

Initial experience of transpapillary gallbladder biopsy using newly designed device delivery system.

Transpapillary gallbladder biopsy has been reported for the diagnosis of gallbladder disease, and this procedure requires special biopsy forceps or a large-diameter pusher catheter. We retrospectively examined consecutive patients who underwent transpapillary gallbladder biopsy using a newly designed device delivery system (Endosheather; Piolax Medical Device, Kanagawa, Japan). We evaluated 11 patients (median age, 71 years [28-85]) who underwent transpapillary gallbladder biopsy from June 2021 to July 2022. The selective gallbladder cannulation and delivery system insertion success rate was 90.9% (10/11). The target lesion biopsy success rate was 63.6% (7/11). The biopsy time (i.e., time to completion of biopsy after successful guidewire placement) was 8.7 (5.4-32.7) min. In 1 patient in whom all 6 gallbladder bile juice cytology results were benign, the biopsy result was suspicious of adenocarcinoma. The final diagnosis for this patient was gallbladder cancer. Adverse events occurred in 2 patients. In 1 patient, acute cholecystitis occurred and required emergency surgery. Transpapillary gallbladder biopsy using the Endosheather is a potential option for the diagnosis of gallbladder disease. A good indication for this technique is considered to be wall thickening at the gallbladder fundus, where it is difficult to differentiate between benign and malignant lesions by imaging modalities such as ultrasonography or endoscopic ultrasound. The addition of transpapillary gallbladder biopsy may be advantageous when performing bile juice cytology using a nasogallbladder drainage tube for the diagnosis of gallbladder disease.

High-brightness scalable continuous-wave single-mode photonic-crystal laser.

Realizing large-scale single-mode, high-power, high-beam-quality semiconductor lasers, which rival (or even replace) bulky gas and solid-state lasers, is one of the ultimate goals of photonics and laser physics. Conventional high-power semiconductor lasers, however, inevitably suffer from poor beam quality owing to the onset of many-mode oscillation1,2, and, moreover, the oscillation is destabilized by disruptive thermal effects under continuous-wave (CW) operation3,4. Here, we surmount these challenges by developing large-scale photonic-crystal surface-emitting lasers with controlled Hermitian and non-Hermitian couplings inside the photonic crystal and a pre-installed spatial distribution of the lattice constant, which maintains these couplings even under CW conditions. A CW output power exceeding 50 W with purely single-mode oscillation and an exceptionally narrow beam divergence of 0.05° has been achieved for photonic-crystal surface-emitting lasers with a large resonant diameter of 3 mm, corresponding to over 10,000 wavelengths in the material. The brightness, a figure of merit encapsulating both output power and beam quality, reaches 1 GW cm-2 sr-1, which rivals those of existing bulky lasers. Our work is an important milestone toward the advent of single-mode 1-kW-class semiconductor lasers, which are expected to replace conventional, bulkier lasers in the near future.

Mapping interindividual dynamics of innate immune response at single-cell resolution.

Common genetic variants across individuals modulate the cellular response to pathogens and are implicated in diverse immune pathologies, yet how they dynamically alter the response upon infection is not well understood. Here, we triggered antiviral responses in human fibroblasts from 68 healthy donors, and profiled tens of thousands of cells using single-cell RNA-sequencing. We developed GASPACHO (GAuSsian Processes for Association mapping leveraging Cell HeterOgeneity), a statistical approach designed to identify nonlinear dynamic genetic effects across transcriptional trajectories of cells. This approach identified 1,275 expression quantitative trait loci (local false discovery rate 10%) that manifested during the responses, many of which were colocalized with susceptibility loci identified by genome-wide association studies of infectious and autoimmune diseases, including the OAS1 splicing quantitative trait locus in a COVID-19 susceptibility locus. In summary, our analytical approach provides a unique framework for delineation of the genetic variants that shape a wide spectrum of transcriptional responses at single-cell resolution.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Maximum phonation time: an independent predictor of late-onset pneumonia after esophageal cancer surgery.

Dysphagia after esophagectomy is a major risk factor for aspiration pneumonia, thus preoperative assessment of swallowing function is important. The maximum phonation time (MPT) is a simple indicator of phonatory function and also correlates with muscle strength associated with swallowing. This study aimed to determine whether preoperative MPT can predict postoperative aspiration pneumonia. The study included 409 consecutive patients who underwent esophagectomy for esophageal cancer between 2017 and 2021. Pneumonia detected by routine computed tomography on postoperative days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later (most often aspiration pneumonia) was defined as late-onset pneumonia. The correlation between late-onset pneumonia and preoperative MPT was investigated. Patients were classified into short MPT (<15 seconds for males and <10 seconds for females, n = 156) and normal MPT groups (≥15 seconds for males and ≥10 seconds for females, n = 253). The short MPT group was significantly older, had a lower serum albumin level and vital capacity, and had a significantly higher incidence of late-onset pneumonia (18.6 vs. 6.7%, P < 0.001). Multivariate analysis showed that short MPT was an independent risk factor for late-onset pneumonia (odds ratio: 2.26, P = 0.026). The incidence of late-onset pneumonia was significantly higher in the short MPT group (15.6 vs. 4.7%, P = 0.004), even after propensity score matching adjusted for clinical characteristics. MPT is a useful predictor for late-onset pneumonia after esophagectomy.

Autoclaving-Triggered Hydrogelation of Chitosan-Gluconic acid Conjugate Aqueous Solution for Wound Healing.

Moist wound healing is known to heal wounds faster than dry wound healing. Hydrogel wound dressings are suitable for moist wound healing because of their hyperhydrous structure. Chitosan, a natural polymer, promotes wound healing by stimulating inflammatory cells and releasing bioactive compounds. Therefore, chitosan hydrogel has great potential as a wound dressing. In our previous study, physically crosslinked chitosan hydrogels were successfully prepared solely by freeze-thawing of chitosan-gluconic acid conjugate (CG) aqueous solution without using any toxic additives. Furthermore, the CG hydrogels could be sterilized by autoclaving (steam sterilization). In this study, we showed that autoclaving (121 °C, 20 min) of a CG aqueous solution simultaneously achieved gelation of the solution and sterilization of the hydrogel. Hydrogelation of CG aqueous solution by autoclaving is also physically crosslinking without any toxic additives. Further, we showed that the CG hydrogels retained favorable biological properties of the CG hydrogels prepared by freeze-thawing and subsequent autoclaving. These results indicated that CG hydrogels prepared by autoclaving were promising as wound dressings.