Identification of a Human Clonogenic Progenitor with Strict Monocyte Differentiation Potential: A Counterpart of Mouse cMoPs.

Monocytes give rise to macrophages and dendritic cells (DCs) under steady-state and inflammatory conditions, thereby contributing to host defense and tissue pathology. A common monocyte progenitor (cMoP) that is strictly committed to the monocyte lineage has been recently identified in mice. Here, we identified human cMoPs as a CLEC12AhiCD64hi subpopulation of conventional granulocyte-monocyte progenitors (cGMPs) in umbilical cord blood and in bone marrow. Human cMoPs gave rise to monocyte subsets without showing any potential for differentiating into myeloid or lymphoid cells. Within the cGMP population, we also identified revised GMPs that completely lacked DC and lymphoid potential. Collectively, our findings expand and revise the current understanding of human myeloid cell differentiation pathways.

Swallowing improvement surgeries.

PURPOSE: To discuss the different swallowing improvement surgeries that address one or more dysfunctional pharyngolaryngeal structures causing dysphagia. These surgeries reduce the risk of aspiration without sacrificing vocal function. METHODS: We searched the PubMed database and used Google Scholar search engine to find studies discussing the different swallowing improvement surgeries. A manual search of references in selected articles and reviews was done as well. No chronologic limitation was set for the studies; however, only articles written in English and Japanese were considered. Due to the nature of this article, no particular inclusion or exclusion criteria were set when searching for studies to be used as references; however, all relevant studies were reviewed and agreed upon by the authors for inclusion in this review article. RESULTS/DISCUSSION: Surgeries to improve swallowing function can be categorized into those that reinforce nasopharyngeal closure or pharyngeal contraction, improve laryngeal elevation or pharyngoesophageal segment opening, and those that improve vocal fold closure to protect the airway during swallowing. They are an effective alternative treatment that may significantly improve these patients' quality of life. Swallowing rehabilitation with the altered pharyngolaryngeal structures is required post-operatively to significantly improve patients' dysphagia. CONCLUSIONS: Surgeries to improve swallowing function address specific dysfunctional sites involved in the swallowing mechanism. Choosing the most appropriate surgery for each patient requires knowledge of the pathophysiology for their dysphagia and detailed pre-operative work-up.

Differences in residual volume above different tracheostomy tube cuffs depending on tube structure, tube tilt angle, and liquid viscosity.

INTRODUCTION: Proper management of aspirated material above the tracheostomy tube cuff is crucial to prevent complications, such as aspiration pneumonia. This study aimed to thoroughly examine the effects of aspirated liquid viscosity, suction port positioning, and tube tilt angle on residual volume above the cuff (RVAC). METHODS: Five types of tracheostomy tubes (approximately 9 mm outer diameter) were placed through a transparent cylinder with an inner diameter of 18 mm. The cuff was inflated to completely seal the interior of the cylinder. Four liquids with different viscosities were poured onto the cuff, and the liquid above the cuff was suctioned from the side port. The cylinder was angled at 90° and 20°, and each test was performed thrice to determine the average RVAC. RESULTS: After side-port suctioning, some liquid residue was observed on the cuff of all tracheostomy tubes. The RVAC increased with higher liquid viscosity. The tubes with a longer distance from the suction port opening to the cuff top exhibited more RVAC. Moreover, the RVAC was almost the same regardless of the cylinder angle for tubes with a suction port on the lateral side. However, tubes with backside ports showed a decreased RVAC with cylinder tilt. CONCLUSIONS: This study underscores the persistence of residual material on cuffed tracheostomy tubes even with regular subglottic secretion drainage. This emphasizes the need for specialized tracheostomy tube development aimed at reducing post-suction RVAC. Improved designs can potentially minimize complications associated with residue accumulation.

Aspiration prevention surgeries: a review.

BACKGROUND: Severe dysphagia can cause intractable pneumonia and lead to life-threatening conditions. Intractable aspiration can occur despite medical management for aspiration prevention. Surgical intervention is indicated for intractable aspiration to prevent potentially life-threatening complications. Since the 1970s, several surgical treatments to prevent aspiration have been reported, and various aspiration prevention surgeries have been introduced, but little is known about them or their benefits. This is a review of the types of aspiration prevention surgery, with the aim of increasing aspiration prevention surgery awareness and their clinical outcomes among medical professionals, which will guide the choices of aspiration prevention surgeries for patients with intractable aspiration. MAIN BODY: Aspiration prevention surgeries can be categorized into three according to their approaches: removal of the larynx, altering the structure of the trachea, and closure of the larynx. Aspiration prevention surgeries to remove the larynx include total and central-part laryngectomy. Aspiration prevention surgeries to alter the structure of the trachea include tracheoesophageal diversion, laryngotracheal separation, and the tracheal flap method. Surgeries to close the larynx can be divided into supraglottic laryngeal closure, glottic laryngeal closure, and subglottic laryngeal closure. Aspiration prevention surgeries prevent aspiration and increase oral intake in 50-80% of patients. Most patients lose vocal function after aspiration prevention surgeries; however, some patients who have undergone total laryngectomy or laryngotracheal separation restored their speech function through tracheoesophageal puncture and use of voice prosthesis. Postoperative suture failure is frequent after epiglottic flap closure and total laryngectomy but rare after central-part laryngectomy, laryngotracheal separation, glottic closure, and subglottic closure. Furthermore, aspiration prevention surgeries improve the quality of life of patients and their caregivers by decreasing suctioning frequency. CONCLUSIONS: In this review, we described the history and development of aspiration prevention surgeries. Medical professionals need to continually improve their knowledge and skills to facilitate appropriate aspiration prevention surgeries according to patient condition.

Longitudinal Analysis of Dysphagia and Factors Related to Postoperative Pneumonia in Patients Undergoing Esophagectomy for Esophageal Cancer.

Few studies have quantified longitudinal changes in swallowing in patients undergoing esophagectomy for esophageal cancer. This study longitudinally analyzed the changes in the Modified Barium Swallow Study Impairment Profile (MBSImP™) scores, swallowing kinematic measurements, and swallowing-related symptoms in patients undergoing esophagectomy. We also examined the association between identified swallowing impairment and aspiration pneumonia after surgery. We included consecutive patients who underwent esophagectomy and completed laryngoscopy and videofluoroscopy before, two weeks, and three months after surgery. We analyzed physiological impairments using the MBSImP. We also assessed the swallowing kinematics on a 5 mL thickened liquid bolus at three time points. Vocal fold mobility was assessed using a laryngoscope. Repeated measures were statistically examined for longitudinal changes in swallowing function. The association between the significant changes identified after esophagectomy and aspiration pneumonia was tested. Twenty-nine patients were included in this study. Preoperative swallowing function was intact in all participants. The timing of swallowing initiation and opening of the pharyngoesophageal segment remained unchanged after surgery. Tongue base retraction and pharyngeal constriction ratio worsened two weeks after surgery but returned to baseline levels three months after surgery. Three months after surgery, hyoid displacement and vocal fold immobility did not fully recover. Aspiration pneumonia occurred in nine patients after surgery and was associated with postoperative MBSImP pharyngeal residue scores. Decreased hyoid displacement and vocal fold immobility were observed postoperatively and persisted for a long time. The postoperative pharyngeal residue was associated with pneumonia and thus should be appropriately managed after surgery.

Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy.

Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients' prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3-6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3-6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome.

CD86-based analysis enables observation of bona fide hematopoietic responses.

Hematopoiesis is a system that provides red blood cells (RBCs), leukocytes, and platelets, which are essential for oxygen transport, biodefense, and hemostasis; its balance thus affects the outcome of various disorders. Here, we report that stem cell antigen-1 (Sca-1), a cell surface marker commonly used for the identification of multipotent hematopoietic progenitors (Lin-Sca-1+c-Kit+ cells; LSKs), is not suitable for the analysis of hematopoietic responses under biological stresses with interferon production. Lin-Sca-1-c-Kit+ cells (LKs), downstream progenitors of LSKs, acquire Sca-1 expression upon inflammation, which makes it impossible to distinguish between LSKs and LKs. As an alternative and stable marker even under such stresses, we identified CD86 by screening 180 surface markers. The analysis of infection/inflammation-triggered hematopoiesis on the basis of CD86 expression newly revealed urgent erythropoiesis producing stress-resistant RBCs and intact reconstitution capacity of LSKs, which could not be detected by conventional Sca-1-based analysis.

Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses.

Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic T cell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival in vivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.

STARDUST SIGN AND RETINAL TEAR DETECTION ON SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: The causes of floaters include posterior vitreous detachment and fundus hemorrhage, both of which are risk factors for retinal tears. We observed the vitreous of patients with floaters using swept source optical coherence tomography. METHODS: Fundus examination was performed, and the vitreous was observed using swept source optical coherence tomography in 202 eyes of 202 patients with floaters. Patients with uveitis, diabetic retinopathy, and other fundus diseases were excluded. RESULTS: Swept source optical coherence tomography revealed posterior vitreous detachment in 145 of 202 eyes (71.8%) and dot reflex like stardust in the vitreous in 42 of 202 eyes (20.8%). Posterior vitreous detachment occurred in 35 of 42 eyes (83.3%) and 110 of 160 eyes (68.8%) in the stardust (+) and stardust (-) groups, respectively; a significant difference was observed (P <0.001). In the stardust (+) group, 11 of 42 eyes (26.2%) had retinal tears with posterior vitreous detachment and 21 of 42 eyes (50.0%) had fundus hemorrhage. Three of 160 eyes (1.9%) and 4 of 160 eyes (2.5%) in the stardust (-) group had retinal tears with posterior vitreous detachment and fundus hemorrhage, respectively. Both tears and fundus hemorrhage were more frequent in the stardust (+) group than in the stardust (-) group (P <0.001). CONCLUSION: The stardust sign on swept source optical coherence tomography indicates the risk of retinal tear.

AI analysis and modified type classification for endocytoscopic observation of esophageal lesions.

Endocytoscopy (EC) facilitates real-time histological diagnosis of esophageal lesions in vivo. We developed a deep-learning artificial intelligence (AI) system for analysis of EC images and compared its diagnostic ability with that of an expert pathologist and nonexpert endoscopists. Our new AI was based on a vision transformer model (DeiT) and trained using 7983 EC images of the esophagus (2368 malignant and 5615 nonmalignant). The AI evaluated 114 randomly arranged EC pictures (33 ESCC and 81 nonmalignant lesions) from 38 consecutive cases. An expert pathologist and two nonexpert endoscopists also analyzed the same image set according to the modified type classification (adding four EC features of nonmalignant lesions to our previous classification). The area under the curve calculated from the receiver-operating characteristic curve for the AI analysis was 0.92. In per-image analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 91.2%, 91.2%, 85.9%, and 83.3%, respectively. The kappa value between the pathologist and the AI, and between the two endoscopists and the AI showed moderate concordance; that between the pathologist and the two endoscopists showed poor concordance. In per-patient analysis, the overall accuracy of the AI, pathologist, and two endoscopists was 94.7%, 92.1%, 86.8%, and 89.5%, respectively. The modified type classification aided high overall diagnostic accuracy by the pathologist and nonexpert endoscopists. The diagnostic ability of the AI was equal or superior to that of the experienced pathologist. AI is expected to support endoscopists in diagnosing esophageal lesions based on EC images.

Safety of surgical tracheostomy under continued antithrombotic therapy: A retrospective cohort study.

OBJECTIVE: Although various guidelines have been established for the management of antithrombotic therapy during surgical treatments, surgical tracheostomy (ST) under continued antithrombotic therapy (CAT) remains challenging. Here, we investigated the risk factors for complications after ST by focusing on the application of CAT during ST. DESIGN: A retrospective cohort study with medical records from 2009 to 2020. SETTING: A single-center study. PARTICIPANTS: This study included patients who had undergone ST at the Department of Otolaryngology of our hospital MAIN OUTCOME MEASURES: The primary outcomes were the incidence of complications and blood test results. Secondary outcomes were risk factors for postoperative complications. RESULTS: We identified 288 patients (median age: 64 years; 184 men [64%]), among whom 40 (median age: 67 years; 29 men [73%]) underwent CAT. Although the patients undergoing CAT had significantly longer activated partial thromboplastin time (p=0.002) and a higher prothrombin time-international normalized ratio (p=0.006) compared to antithrombotic naïve patients, no statistically significant intergroup differences were observed for the risk of bleeding, infection, or subcutaneous emphysema. Instead, ST under local anesthesia (p=0.01) and ST for airway emergency (p=0.02) significantly increased the risk of early postoperative complications. CONCLUSION: These results suggest that ST under CAT can be safely performed without any increased risk of postoperative complications. Nevertheless, surgeons should be extra cautious about early complications after ST under local anesthesia without intubation or ST for airway emergencies.

Experimental Observation of Long-Range Magnetic Order in Icosahedral Quasicrystals.

Quasicrystals (QCs), first discovered in 1984, generally do not exhibit long-range magnetic order. Here, we report on long-range magnetic order in the real icosahedral quasicrystals (i QCs) Au-Ga-Gd and Au-Ga-Tb. The Au65Ga20Gd15 i QC exhibits a ferromagnetic transition at TC = 23 K, manifested as a sharp anomaly in both magnetic susceptibility and specific heat measurements, along with an appearance of magnetic Bragg peak below TC. This is the first observation of long-range magnetic order in a real quasicrystal, in contrast to the spin-glass-like behaviors observed for the other magnetic quasicrystals found to date. Moreover, when Gd is replaced by Tb, i.e., for the Au65Ga20Tb15 i QC, a ferromagnetic behavior is still retained with TC = 16 K. Although the sharp anomaly in the specific heat observed for the Au65Ga20Gd15 i QC becomes broadened upon Tb substitution, neutron diffraction experiments clearly show marked development of magnetic Bragg peaks just below TC, indicating long-range magnetic order for the Au65Ga20Tb15 i QC also. Our findings can contribute to the further investigation of exotic magnetic orders formed on real quasiperiodic lattices with unprecedented highest global symmetry, i.e., icosahedral symmetry.

A novel needle electrode for intraoperative fourth cranial nerve neurophysiological mapping.

OBJECTIVES: Trochlear nerve (CN-IV) mapping method has not been confirmed to date. The compound muscle action potential (CMAP) of CN-IV cannot be recorded because of the low mapping sensitivity and anatomical characteristics of the superior oblique muscle (SOM). The aim of this study was to evaluate the effectiveness of a novel needle electrode (NNE), for the intraoperative mapping of CN-IV. MATERIALS AND METHODS: The NNEs were inserted in the target extraocular muscles in 19 patients. We compared the CMAP amplitude of the NNE with that of the conventional needle electrode (CNE). Furthermore, we investigated the dissimilarity between the CMAP of the CN-IV and other extraocular cranial nerves (ECNs) and the correlation between the readings of the CN-IV mapping and its postoperative functional outcome. RESULTS: The CMAP of CN-IV has been measured in nine patients (47.4%). The CMAP of CN-IV was distinguishable from other ECNs. The CMAP of the NNE was found to be three times higher than that of the CNE. Although the NNE has shown the potential to record the CN-IV's CMAP, 4 cases ended up having a CN-IV postoperative dysfunction. CONCLUSIONS: For the first time, we confirmed the possibility of intraoperative mapping the CN-IV using an NNE inserted into the SOM. The NNE can also be useful for other neurophysiological monitoring methods.

Aspiration Prevention Surgery under Local Anesthesia for Palliative Care in Patients with Head and Neck Cancer: A Report of Two Cases.

Aspiration prevention (AP) surgery may improve the quality of life (QOL) of patients with severe dysphagia. However, not all patients can endure this type of surgery under general anesthesia because of their poor status. Herein, we describe the cases of 2 patients with head and neck cancer (HNC) who underwent AP surgery for palliative care. Although both patients had tracheostomy due to severe dysphagia and respiratory impairment and frequently needed suction, they were successfully managed with AP surgery under local anesthesia. A tracheostoma was reshaped to be sufficiently large for an airway to be secured without a cannula. Their respiratory failure gradually improved, and suction frequency markedly decreased after surgery; thus, they could receive medical treatment at home. When patients with HNC under palliative care have a tracheal cannula and cannot vocalize, AP surgery under local anesthesia is an option to improve their QOL.

[Ependymoma of the Sella Turcica and Suprasellar Region].

An ependymoma of the sella turcica and the suprasellar region has been described by only 10 reports in the available literature. We describe similar pathology in a 70-year-old woman who presented with dementia and visual disturbance. Magnetic resonance imaging with gadolinium revealed a mixed contrast-enhanced lesion(maximum diameter 3.5 cm)in the sella turcica and suprasellar area associated with a noncommunicating hydrocephalus. The patient was preoperatively presumptively diagnosed with a craniopharyngioma. The lesion was adherent to the hypothalamus, and the third ventricular floor was completely resected via an endoscopic endonasal transsphenoidal approach. Histopathological findings confirmed an ependymoma. Although her visual disturbance improved, the patient developed postoperative panhypopituitarism. She has had no recurrence for 7 years postoperatively. An ependymoma of the sella turcica and the suprasellar region is extremely rare; establishing the preoperative diagnosis is challenging in such patients. Maximum tumor resection and long-term follow-up are essential for good prognosis.

[Conversion Surgery following Second-Line Chemotherapy for Unresectable Gastric Cancer].

We retrospectively analyzed clinicopathological and survival data of 8 patients with unresectable gastric cancer who underwent conversion surgery(CS)following second-line chemotherapy from April 2013 to December 2020. There were 7 males and 1 female patients with a median age of 69(64-76)years old. Five patients had 1 unresectable factor, 2 had 2 unresectable factors, and 1 had 3 unresectable factors. All patients achieved R0 resection. The median survival time(MST) of patients with CS following second-line chemotherapy was significantly longer than that without CS(73.4 vs 12.3 months, respectively). The MST of patients with CS following first-line chemotherapy was significantly longer than that without CS (22.9 vs 12.3 months, respectively). This study suggested that CS following first- or second-line chemotherapy may improve survival duration for unresectable gastric cancer.

[Two Cases of Esophageal Neuroendocrine Carcinoma That Were Successfully Controlled by Multi-Modality Therapy].

Esophageal neuroendocrine carcinoma is extremely rare, and its treatment strategy has not been established. We report 2 cases esophageal neuroendocrine carcinoma. Case 1: A 74-year-old man was diagnosed as having esophageal neuroendocrine carcinoma(clinical T3N4M0, Stage Ⅳa). He received 60 Gy of radiation therapy with etoposide(100 mg/m2)plus cisplatin(80 mg/m2). No recurrence has been detected 1 year after treatment. Case 2: A 78-year-old man was diagnosed as esophageal neuroendocrine carcinoma(clinical T3N0M0, Stage Ⅱ). He underwent esophagectomy with 3 field lymph nodes dissection. Adjuvant chemotherapy was administered with irinotecan(60 mg/m2)plus cisplatin(60 mg/m2). After chemotherapy, he survived 1 year without recurrence.

[Changes in Renal Function and Feasibility of Adjuvant Chemotherapy for Colorectal Cancer Patients with Diverting Ileostomy after Ileal Pouch-Anal Anastomosis].

We investigated changes in estimated glomerular filtration rate(eGFR)in 11 colorectal cancer patients(6 familial adenomatous polyposis, 5 ulcerative colitis)who underwent restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA) and diverting ileostomy(DI), the tolerability and adverse events of adjuvant chemotherapy(ACT)in 4 cases. After IPAA, eGFR decreased significantly(p=0.02)and did not return to the preoperative level even after stoma closure(p<0.01). mFOLFOX6 was selected as the regimen in 4 candidates, and no significant changes in eGFR after ACT were observed. The relative dose intensity of oxaliplatin was 91.7%, and no gastrointestinal adverse events of Grade 3 or higher were observed. Although in a small number of cases, mFOLFOX6 as ACT after IPAA and DI may be feasible.

Comparison of the ischemic and non-ischemic lung cancer metabolome reveals hyper activity of the TCA cycle and autophagy.

Recent advances in cancer biology reveal the importance of metabolic changes in cancer; however, less is known about how metabolic pathways in tumors are regulated in vivo. Here, we report analysis of the lung cancer metabolism based on different surgical procedures, namely lobectomy and partial resection. In lobectomy, but not in partial resection, pulmonary arteries and veins are ligated prior to removal of tissues, rendering tissues ischemic. We show that tumors indeed undergo ischemia upon lobectomy and that the tumor metabolome differs markedly from that of tumors removed by partial resection. Comparison of the responses to ischemia in tumor and normal lung tissues revealed that lung cancer tissue exhibits greater TCA cycle and autophagic activity than do normal lung tissues in vivo in patients. Finally, we report that deleting ATG7, which encodes a protein essential for autophagy, antagonizes growth of tumors derived from lung cancer cell lines, suggesting that autophagy confers metabolic advantages to lung cancer. Our findings shed light on divergent metabolic responses to ischemia seen in tumors and normal tissues.

Prominent role for plasmacytoid dendritic cells in mucosal T cell-independent IgA induction.

Although both conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) are present in the gut-associated lymphoid tissues (GALT), the roles of pDCs in the gut remain largely unknown. Here we show a critical role for pDCs in T cell-independent (TI) IgA production by B cells in the GALT. When pDCs of the mesenteric lymph nodes (MLNs) and Peyer's patches (PPs) (which are representative GALT) were cultured with naive B cells to induce TI IgA class switch recombination (CSR), IgA production was substantially higher than in cocultures of these cells with cDCs. IgA production was dependent on APRIL and BAFF production by pDCs. Importantly, pDC expression of APRIL and BAFF was dependent on stromal cell-derived type I IFN signaling under steady-state conditions. Our findings provide insight into the molecular basis of pDC conditioning to induce mucosal TI IgA production, which may lead to improvements in vaccination strategies and treatment for mucosal-related disorders.