Nasolacrimal Duct Obstruction Secondary to Eosinophilic Chronic Rhinosinusitis: A Case Report.

A 47-year-old Japanese woman presented with a 1-year history of right-sided epiphora. On initial consultation, the patient had a high right tear meniscus height. CT images revealed bilateral soft tissue opacification in the nasal cavity and maxillary, frontal, and ethmoid sinuses. The lesion in the right nasal cavity and maxillary sinus involved the right lacrimal sac and nasolacrimal duct. Blood test results showed elevated eosinophil count. Endoscopic sinus surgery and excisional biopsy of the nasolacrimal duct were performed. Histopathological examinations of the excised right nasolacrimal duct and nasal polyps from the nasal cavity and maxillary sinus showed high levels of eosinophilic inflammatory infiltrates. The definite diagnosis of eosinophilic chronic rhinosinusitis was made, based on clinical, radiological, and histopathological findings. At 1.5-year follow-up, tear meniscus height was normal, the lacrimal drainage system remained patent, and the rhinosinusitis did not recur.

Successful treatment with atezolizumab combination chemotherapy in a patient with high-grade fetal adenocarcinoma of the lung: A case report.

High-grade fetal lung adenocarcinoma (H-FLAC) is a rare tumor, with little known of its response to chemotherapy with or without an immune checkpoint inhibitor or of its molecular profile. We report the first case of a 56-year-old man with stage IV H-FLAC who was successfully treated with carboplatin plus nab-paclitaxel in combination with atezolizumab. In addition, the tumor was found to be positive for amplification of the human epidermal growth factor receptor 2 gene.

Treatment with Sotrovimab and Casirivimab/Imdevimab Enhances Serum SARS-CoV-2 S Antibody Levels in Patients Infected with the SARS-CoV-2 Delta, Omicron BA.1, and BA.5 Variants.

Background: The neutralizing ability of sotrovimab and casirivimab/imdevimab against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is attenuated in the subvariant BA.5. However, the efficacy of sotrovimab in the clinical setting remains to be investigated. Methods: Patients admitted to Kishiwada City Hospital with COVID-19 delta, omicron BA.1, or BA.5 subvariants were evaluated retrospectively for serum SARS-CoV-2 S and N antibody levels using the Elecsys Anti-SARS-CoV-2 assay. Results: In patients with COVID-19 during the BA.5 wave of the COVID-19 pandemic, anti-SARS-CoV-2 S antibody titers (median [interquartile range]) increased from 2154.0 (864.0−6669.3) U/mL on day 0 to 21,371.0 (19,656.3−32,225.0) U/mL on day 3 in the group treated with sotrovimab (N = 40) and were significantly higher than in the group treated with remdesivir plus dexamethasone plus baricitinib (p < 0.001). Conclusion: Treatment with sotrovimab could prevent severe disease in high-risk patients infected with SARS-CoV-2 subvariant BA.5.

The safety and efficacy of durvalumab consolidation therapy in the management of patients with stage III non-small-cell lung cancer and preexisting interstitial lung disease.

BACKGROUND: Some lung cancer patients have preexisting interstitial lung disease (ILD), which is considered a risk factor for lung cancer treatment. This study investigated the safety and efficacy of durvalumab consolidation therapy for patients with stage III non-small-cell lung cancer (NSCLC) and preexisting ILD. METHODS: Fifty consecutive patients who were judged to be tolerable to concurrent chemoradiotherapy (CCRT) for stage III NSCLC were enrolled. Differences in the incidence rate of radiation pneumonitis (RP) and progression-free survival (PFS) were assessed in patients with or without ILD of which CT showed non-usual interstitial pneumonia pattern between the durvalumab consolidation group and chemotherapy (combination of carboplatin and paclitaxel [CP]) consolidation group. RESULTS: The incidence of RP was higher in patients with preexisting ILD (40% and 20% in the durvalumab and CP groups, respectively) than in those without ILD (26% and 8% in the durvalumab and CP groups, respectively). Univariate analysis showed that durvalumab therapy tended to increase the incidence of RP; however, preexisting ILD did not significantly increase the incidence of RP. The condition of all patients who developed RP improved with the administration of oral prednisolone. Among patients without ILD, the median PFS was 17 and 16 months in the durvalumab and CP groups, respectively. Among patients with preexisting ILD, median PFS was not achieved in the durvalumab group and was 8 months in the CP group. CONCLUSIONS: Although durvalumab consolidation therapy tended to increase the incidence of RP, it might be tolerable in stage III NSCLC patients with preexisting ILD.

Upregulation of viral RNA polymerase activity promotes adaptation of SSPE virus to neuronal cells.

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurodegenerative disease caused by measles virus variants (SSPE viruses) that results in eventual death. Amino acid substitution(s) in the viral fusion (F) protein are key for viral propagation in the brain in a cell-to-cell manner, a specific trait of SSPE viruses, leading to neuropathogenicity. In this study, we passaged an SSPE virus in cultured human neuronal cells and isolated an adapted virus that propagated more efficiently in neuronal cells and exhibited increased cell-to-cell fusion. Contrary to our expectation, the virus harbored mutations in the large protein, a viral RNA-dependent RNA polymerase, and in the phosphoprotein, its co-factor, rather than in the F protein. Our results imply that upregulated RNA polymerase activity, which increases F protein expression and cell-to-cell fusion, could be a viral factor that provides a growth advantage and contributes to the adaptation of SSPE viruses to neuronal cells.

Aluminium Gauze Reduces SARS-CoV-2 Viral Load in Non-Woven Masks Worn by Patients with COVID-19.

BACKGROUND: Aluminium reduces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) survival in experimental settings. It is unknown whether adding an aluminium gauze to a mask reduces the SARS-CoV-2 RNA load in the mask and whether SARS-CoV-2 is detectable in the breath that permeates through such a mask in clinical settings. METHODS: Patients admitted to Kishiwada City Hospital, Osaka, Japan, between July 2021 and September 2021 were enrolled in the study. Non-woven masks comprising filters with 99% viral filtration efficacy and aluminium and cotton gauzes attached to plastic collection cases were developed. All participants wore the experimental mask models for three hours. RESULTS: Twenty-nine patients who wore the final model masks were analysed in this study. The Ct values of the nucleocapsid gene and envelope gene of SARS-CoV-2 were significantly higher in the aluminium gauze than in the cotton gauze. SARS-CoV-2 RNA was detected in the masks of 8 out of 12 vaccinated patients (66.7%). Although breath condensates were collected behind both aluminium and cotton gauzes, SARS-CoV-2 RNA was not detected in these condensates. CONCLUSIONS: Our study indicated that non-woven masks with an aluminium gauze may obstruct SARS-CoV-2 transmission in clinical settings better than non-woven masks with cotton gauzes.

Efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic adults with COVID-19: A retrospective study.

BACKGROUND: Remdesivir with dexamethasone and remdesivir with baricitinib are effective in coronavirus disease 2019 (COVID-19) patients. However, there has been few evidence regarding the efficacy of the combination of baricitinib, remdesivir, and dexamethasone in hypoxic COVID-19 patients. METHODS: Consecutive patients who required oxygen therapy at the time of admission and received remdesivir and dexamethasone at Kishiwada City Hospital between March 1, 2021 and May 31, 2021 were retrospectively analyzed. RESULTS: A total of 90 patients were investigated, including 30 receiving a combination of remdesivir, dexamethasone, and baricitinib (baricitinib group) and 60 receiving remdesivir and dexamethasone (control group). The use of direct oral anticoagulants, the level of C-reactive protein, and chest X-ray abnormalities were significantly higher in the baricitinib group than in the control group. Patients in the baricitinib group recovered a median of four days faster than those in the control group (median, 7 days vs. 11 days; Gray's test, p < 0.001). The recovery rate was 90.0% in the baricitinib group and 63.3% in the control group (p = 0.011). Fine and Gray regression analysis showed that adjusted rate ratio for recovery with the baricitinib combination therapy was 5.26 (95% confidential interval, 1.99-13.9; p < 0.001). The incidence of new onset of bacterial infection was 6.7% in the baricitinib group and 16.7% in the control group (p = 0.324). CONCLUSIONS: Our study suggests that the combination of baricitinib, dexamethasone, and remdesivir is effective and tolerable in hypoxic patients with COVID-19.

Successful laparoscopic lavage and drainage for intestinal perforation in a patient with COVID-19: A case report.

INTRODUCTION: Some patients with coronavirus disease 2019 (COVID-19) have acute abdomen and need surgery. However, surgery in the acute phase of COVID-19 is associated with worse postoperative outcomes and an increased risk of mortality. We report a case of a patient with COVID-19 who developed intestinal perforation that was treated acutely with antibiotics and delayed surgical intervention. PRESENTATION OF CASE: A 79-year-old man with COVID-19 was treated with remdesivir and dexamethasone, and his respiratory symptoms and hypoxia improved. However, abdominal symptoms developed, and intestinal perforation occurred. As the nasopharyngeal swab PCR test was positive for SARS-CoV-2, conservative treatment with tazobactam/piperacillin was started to avoid surgery in the acute phase of COVID-19. An intraperitoneal abscess was confirmed on follow-up computed tomography. Emergent laparoscopic lavage and drainage, and transverse colon stoma construction were performed with medical staff using full personal protective equipment. Bacterial culture from the ascites detected Escherichia coli and Bacteroides. The SARS-CoV-2 PCR test of the ascites sample was negative. No infection was observed in the medical staff. DISCUSSION: COVID-19 has been associated with a higher perioperative risk and postoperative mortality. There has also been a report of ascitic fluid testing positive for SARS-CoV-2 on PCR, suggesting the possibility of intraoperative aerosolization. Avoiding surgical treatment in the acute phase of COVID-19 may reduce deaths from perioperative complications. CONCLUSION: Our case suggests that in acute COVID-19 lung infection, careful observation and delayed surgical treatment could prevent worsening of the COVID-19 and reduce the risk of infection to the medical staff.

Post-COVID-19 interstitial lung disease presenting with profound hypoxemia: Report of three cases demonstrating a good response to high-dose corticosteroid therapy.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which leads to critical pneumonia, although the clinical courses vary. In some cases, COVID-19 pneumonia causes secondary pulmonary fibrosis, which can retain radiological changes and prolong respiratory symptoms. Interstitial lung disease (ILD) secondary to COVID-19 is thought to be caused by multiple pathologies, such as excessive cytokines and abnormal repair processes elaborated by lung cells (epithelium, mesenchyme, and alveolar macrophages) after lung injury rather than viral invasion itself. Immunosuppression therapy may improve chronic respiratory symptoms and radiological changes in post-COVID-19 ILD, although the treatment is not yet established. Herein, we report three patients with post-COVID-19 ILD who presented with profound hypoxemia that had a good response to high-dose corticosteroid therapy. Further and larger studies are needed to establish post-COVID-19 ILD.

Successful treatment with metronidazole and paromomycin for fulminant amoebic colitis during cytotoxic chemotherapy in a patient with small-cell lung cancer.

We report the case of a 64-year-old man with advanced small-cell lung cancer who developed fulminant amoebic colitis during cytotoxic chemotherapy. During the first cycle of carboplatin/etoposide treatment, febrile neutropenia and grade 4 neutropenia developed. Because diarrhea, abdominal pain, and bloody stool were observed, abdominal computed tomography was performed, showing intussusception, and extensive colectomy and colostomy were performed. Histopathology of the colon revealed gastrointestinal necrosis and perforation due to Entamoeba histolytica infection. Amoebiasis improved after treatment with metronidazole and paromomycin. The second cycle of carboplatin/etoposide with dose reduction was completed, resulting in a partial response to small-cell lung cancer. The results of this case suggest that paromomycin is an additional option for amoebiasis during cytotoxic chemotherapy, and persistent diarrhea during cytotoxic chemotherapy should alert clinicians to consider the development of amoebiasis.

Common and unique strategies of myoglobin evolution for deep-sea adaptation of diving mammals.

Myoglobin (Mb) is highly concentrated in the myocytes of diving mammals such as whales and seals, in comparison with land animals, and its molecular evolution has played a crucial role in their deep-sea adaptation. We previously resurrected ancestral whale Mbs and demonstrated the evolutional strategies for higher solubility under macromolecular crowding conditions. Pinnipeds, such as seals and sea lions, are also expert diving mammals with Mb-rich muscles. In the present study, we resurrected ancestral pinniped Mbs and investigated their biochemical and structural properties. Comparisons between pinniped and whale Mbs revealed the common and distinctive strategies for the deep-sea adaptation. The overall evolution processes, gaining precipitant tolerance and improving thermodynamic stability, were commonly observed. However, the strategies for improving the folding stability differed, and the pinniped Mbs exploited the shielding of hydrophobic surfaces more effectively than the whale Mbs.

Ulcerative colitis-related severe enteritis: an infrequent but serious complication after colectomy.

BACKGROUND AND AIM: After colectomy for ulcerative colitis (UC), very severe and sometimes lethal enteritis can develop. However, the clinical features remain uncertain because of the low incidence, diversity of symptoms, and undefined diagnostic criteria. The aim of this study was to define postoperative ulcerative colitis-related severe enteritis (UCRSE) and to investigate its clinical features. METHODS: A retrospective multicenter study was performed as a survey of major medical facilities utilizing surgical supplies for inflammatory bowel disease in Japan from 2001 to 2014. UCRSE was defined as a case with massive intestinal bleeding, intestinal perforation, high-output stoma, and/or a requirement for medications, such as steroids and biologics. Patients with gastroduodenal lesions or pouchitis alone were excluded. The incidence, symptoms, involvement of bacteria, cytomegalovirus reactivation, treatment, and prognosis were examined for patients with UCRSE after colectomy. RESULTS: Forty-two (0.8%) out of 5284 cases met the criteria for UCRSE. Major symptoms were massive intestinal bleeding (76.2%), which required a median of 3850 (560-18900) mL blood transfusion; high-output stoma (38.1%) with excretion of fluid of 5000 (2000-7800) mL/day; and intestinal perforation (7.1%). Hypovolemic shock (35.7%) and/or disseminated intravascular coagulation (31.0%) developed as serious complications. Tests for cytomegalovirus reactivation were positive in 26.2% of cases. The presence of pathogenic bacteria was confirmed in only 5 cases. Corticosteroids or infliximabs were effective in half of the patients. Thirteen cases (31.0%) were treated surgically and 22 cases (56.4%) required maintenance therapy. The mortality rate was 11.9%. CONCLUSION: UCRSE is a rare but serious complication after colectomy and is sometimes life-threatening.

Toll-like receptor 2 mediates the immune response of the bovine oviductal ampulla to sperm binding.

We previously reported that sperm binding to cultured bovine oviduct epithelial cells induces an anti-inflammatory immune response. Now we have developed a differentiated explant model to focus on the oviductal ampulla, where fertilization occurs, and to study the effect of sperm capacitation on the immune response. We used heparin to stimulate bovine sperm capacitation. Fluorescence imaging showed that 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide-labeled sperm pretreated with (Hep(+) ) or without (Hep(-) ) heparin rapidly attached to the explant ciliated epithelium in similar numbers. However, only Hep(+) sperm upregulated explant messenger RNA (mRNA) transcription of TLR2, IL8, TGFB1, and PGES, without changes in TNFA and IL-10 expression, while Hep(-) sperm only upregulated PGES. The responses were primarily anti-inflammatory, with a greater response produced by Hep(+) sperm, which also produced a substantial increase in TLR2 protein expression in the epithelium. The addition of TLR1/2 (toll-like receptor 1/2) antagonist to the Hep(+) and (Hep(-) ) sperm-explant coincubations reduced sperm attachment to the epithelium and inhibited TLR2 protein expression and some of the Hep(+) sperm-induced mRNA transcription. Our observations suggest that the ampullar epithelium immunologically reacts more strongly to sperm that have undergone heparin stimulation of capacitation. This anti-inflammatory response could serve to protect capacitated sperm as they approach the oocyte in the ampulla.

Bronchoscopic Surgery for a Solitary Tracheal Tumor of Tracheobronchopathia Osteochondroplastica.

Tracheobronchopathia osteochondroplastica is a rare benign condition in which multiple cartilaginous or bony submucosal nodules project into the trachea or bronchi. A 71-year-old man complained of cough for 3 months. Computed tomography scanning revealed a calcified tracheal tumor near the tracheal bifurcation. Pulmonary function testing indicated airflow limitation, and bronchoscopic examination confirmed a solitary rigid tumor. Bronchoscopic resection was performed under general anesthesia, and the tumor was detached by cauterizing its stem with high-frequency coagulation. The tumor was pathologically indicative of tracheobronchopathia osteochondroplastica. After surgery, the clinical signs of cough and dyspnea resolved and pulmonary function normalized.

Bovine oviduct epithelial cells suppress the phagocytic activity of neutrophils towards sperm but not for bacteria in vitro: Immunofluorescence and electron microscopic observations.

Previously, we reported that polymorphonuclear neutrophils (PMNs) are constantly existent in the bovine oviduct fluid during the pre-ovulatory stage under physiological conditions. Moreover, incubation of PMNs with bovine oviduct epithelial cells-conditioned medium (BOEC-CM) resulted in suppression of their phagocytic activity for sperm. During pathophysiological conditions, cows may be inseminated by infected semen which exposes oviductal PMNs to allogenic sperm simultaneously with pathogens. This study aimed to visually investigate the role of oviduct epithelium in regulating the phagocytic behavior of PMNs toward sperm as a physiological stimulus, with Escherichia coli (E. coli) as a pathological stimulus. In our experiment, PMNs were incubated for 2 h in BOEC-CM. Phagocytosis was then assayed by co-incubation of these PMNs either with sperm, E. coli, or latex beads. BOEC-CM significantly suppressed the direct phagocytosis of PMNs for sperm, but did not affect their phagocytic activity for E. coli or latex beads. Additionally, an investigation with scanning electron microscopy revealed that BOEC-CM suppressed the formation of DNA-based neutrophil extracellular traps (NETs) for sperm entanglement. BOEC-CM did not alter NETs formation towards E. coli. A quantification of NETs formation using an immunofluorescence microscopy showed that the areas of NETs formation for E. coli were significantly larger than those formed for sperm. Our data clearly show that the bovine oviduct, through secretions, protects sperm from phagocytosis by PMNs and eliminates bacterial dissemination through maintaining the phagocytic activity of PMNs towards bacteria.

Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation.

We previously reported that sperm binding to cultured monolayers of bovine uterine epithelial cells induces an acute inflammatory response involving the Toll-like receptor (TLR2) signaling pathway. This response serves to clear the uterus of sperm and thereby prepares the endometrium for implantation. The endometrium is lined by surface epithelial cells; however, epithelial cells also line uterine glands. To investigate the source of the immune response, we used an explant model. Explants of bovine endometrium were incubated with bull sperm illuminated by JC1 fluorescent labeling in their mitochondria. The sperm glided over the surface epithelium until they encountered and entered uterine glands, where they remained. Scanning electron microscopy of explants revealed polymorphonuclear neutrophils (PMNs) in uterine glands along with sperm. In the absence of sperm, PMNs were not seen in glands. The incubation of sperm with explants resulted in an acute inflammatory response, seen as the upregulation of mRNA expression of IL8, TNFA, IL1B, PGES and TLR2 in whole explants, as well as increased TNFA protein expression in uterine glands. TLR1/2 antagonist reduced sperm numbers in the glands and inhibited the increase of TNFA. Our observations suggest that uterine glands serve as a site where sperm interact with the uterine epithelium to trigger the innate immune response to clear excess sperm from the uterus.

Tracing whale myoglobin evolution by resurrecting ancient proteins.

Extant cetaceans, such as sperm whale, acquired the great ability to dive into the ocean depths during the evolution from their terrestrial ancestor that lived about 50 million years ago. Myoglobin (Mb) is highly concentrated in the myocytes of diving animals, in comparison with those of land animals, and is thought to play a crucial role in their adaptation as the molecular aqualung. Here, we resurrected ancestral whale Mbs, which are from the common ancestor between toothed and baleen whales (Basilosaurus), and from a further common quadrupedal ancestor between whale and hippopotamus (Pakicetus). The experimental and theoretical analyses demonstrated that whale Mb adopted two distinguished strategies to increase the protein concentration in vivo along the evolutionary history of deep sea adaptation; gaining precipitant tolerance in the early phase of the evolution, and increase of folding stability in the late phase.

Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PURPOSE: The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. METHODS: We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. RESULTS: Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). CONCLUSION: The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

Evidence-based clinical practice guidelines for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

[A Resected Case of Cancer in the Ileum of the Blind Loop after an Ileotransverse Colostomy].

We report a resected case of cancer at the ileum of the blind loop. An 81-year-old male underwent an appendectomy for acute appendicitis and an ileotransverse colostomy for postoperative obstruction when he was 14 years old. He underwent radiation therapy for prostate cancer when he was 75 years old. Six years later, enhanced computed tomography revealed a 7 cm mass in the ileum of the blind loop. Colonoscopy showed wall thickening at the ileum of the blind loop, and biopsy revealed an adenocarcinoma. We performed partial resection of the ileum. The patient was discharged 17 days after surgery. Cancer at the ileum of the blind loop after an ileotransverse colostomy has rarely been reported.