Nafamostat mesylate decreases skin flap necrosis in a mouse model of type 2 diabetes by protecting the endothelial glycocalyx.

The success rate of flap tissue reconstruction has increased in recent years owing to advancements in microsurgical techniques. However, complications, such as necrosis, are still more prevalent in diabetic patients compared to non-diabetic individuals, presenting an ongoing challenge. To address this issue, many previous studies have examined vascular anastomoses dilation and stability, primarily concerning surgical techniques or drugs. In contrast, in the present study, we focused on microvascular damage of the peripheral microvessels in patients with diabetes mellitus and the preventative impact of nafamostat mesylate. Herein, we aimed to investigate the effects of hyperglycemia on glycocalyx (GCX) levels in mice with type 2 diabetes. We examined the endothelial GCX (eGCX) in skin flap tissue of 9-12-week-old type 2 diabetic mice (db/db mice) using a perforator skin flap and explored treatment with nafamostat mesylate. The growth rates were compared after 1 week. Heterotype (db/+) mice were used as the control group. Morphological examination of postoperative tissues was performed at 1, 3, 5, and 7 days post-surgery. In addition, db/db mice were treated with 30 mg/kg/day of nafamostat mesylate daily and were evaluated on postoperative day 7. Seven days after surgery, all db/db mice showed significant partial flap necrosis. Temporal observation of the skin flaps revealed a stasis-like discoloration and necrosis starting from the contralateral side of the remaining perforating branch. The control group did not exhibit flap necrosis, and the flap remained intact. In the quantitative assessment of endothelial glycans using lectins, intensity scoring showed that the eGCX in the db/db group was significantly thinner than that in the db/+ group. These results were consistent with the scanning electron microscopy findings. In contrast, treatment with nafamostat mesylate significantly improved the flap engraftment rate and suppressed eGCX injury. In conclusion, treatment with nafamostat mesylate improves the disrupted eGCX structure of skin flap tissue in db/db mice, potentially ameliorating the impaired capillary-to-venous return in the skin flap tissue.

Urinary liver-type fatty acid-binding protein levels may be associated with the occurrence of acute kidney injury induced by trauma.

Introduction: Acute kidney injury (AKI), with a fatality rate of 8.6%, is one of the most common types of multiorgan failure in the intensive care unit (ICU). Thus, AKI should be diagnosed early, and early interventions should be implemented. Urinary liver-type fatty acid-binding protein (L-FABP) could aid in the diagnosis of AKI. Methods: In this prospective, single-center, observational study, we included 100 patients with trauma. Urinary L-FABP levels were measured using a semi-quantitative rapid assay kit 6 and 12 h after injury. Negative, weakly positive, and strongly positive urinary L-FABP levels were examined using two protocols. Using protocol 1, measurements were performed at 6 h after injury negative levels were considered "negative," and weakly positive and strongly positive levels were considered "positive." Using protocol 2, strongly positive levels at 6 h after injury were considered "positive," and negative or weakly positive levels at 6 h after injury were considered "positive" if they were weakly positive or positive at 12 h after injury. Results: Fifteen patients were diagnosed with AKI. Using protocol 1, the odds ratio (OR) was 20.55 (p = 0.001) after adjustment for the injury severity score (ISS), contrast media use, and shock index. When the L-FABP levels at 6 and 12 h were similarly adjusted for those three factors, the OR was 18.24 (p < 0.001). The difference in ORs for protocols 1 and 2 was 1.619 (p = 0.04). Discussion: Associations between urinary L-FABP and AKI can be examined more precisely by performing measurements at 6 and 12 h after injury than only one time at 6 h.

A Case of Tick-borne Disease with Yezo Virus and Borrelia miyamotoi Coinfection.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by PCR and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

Endothelial Glycocalyx in the Peripheral Capillaries is Injured Under Oxaliplatin-Induced Neuropathy.

Oxaliplatin, a platinum-based anticancer drug, is associated with peripheral neuropathy (oxaliplatin-induced peripheral neuropathy, OIPN), which can lead to worsening of quality of life and treatment interruption. The endothelial glycocalyx, a fragile carbohydrate-rich layer covering the luminal surface of endothelial cells, acts as an endothelial gatekeeper and has been suggested to protect nerves, astrocytes, and other cells from toxins and substances released from the capillary vessels. Mechanisms underlying OIPN and the role of the glycocalyx remain unclear. This study aimed to define changes in the three-dimensional ultrastructure of capillary endothelial glycocalyx near nerve fibers in the hind paws of mice with OIPN. The mouse model of OPIN revealed disruption of the endothelial glycocalyx in the peripheral nerve compartment, accompanied by vascular permeability, edema, and damage to the peripheral nerves. To investigate the potential treatment interventions, nafamostat mesilate, a glycocalyx protective agent was used in tumor-bearing male mice. Nafamostat mesilate suppressed mechanical allodynia associated with neuropathy. It also prevented intra-epidermal nerve fiber loss and improved vascular permeability in the peripheral paws. The disruption of endothelial glycocalyx in the capillaries that lie within peripheral nerve bundles is a novel finding in OPIN. Furthermore, these findings point toward the potential of a new treatment strategy targeting endothelial glycocalyx to prevent vascular injury as an effective treatment of neuropathy as well as of many other diseases. PERSPECTIVE: OIPN damages the endothelial glycocalyx in the peripheral capillaries, increasing vascular permeability. In order to prevent OIPN, this work offers a novel therapy approach that targets endothelial glycocalyx.

Recombinant antithrombin attenuates acute kidney injury associated with rhabdomyolysis: an in vivo animal study.

BACKGROUND: Rhabdomyolysis is characterized by the destruction and necrosis of skeletal muscle tissue, resulting in acute kidney injury (AKI). Recombinant antithrombin (rAT) has DNA repair and vascular endothelial-protection properties. Herein, we investigated whether rAT therapy has beneficial effects against rhabdomyolysis-induced AKI. Ten-week-old male B6 mice were injected with 5 mL/kg of 50% glycerol intramuscularly in the left thigh after 24 h of fasting to create a rhabdomyolysis mouse model. Further, 750 IU/kg rAT was injected intraperitoneally at 24 and 72 h after the rhabdomyolysis model was established. The mice were euthanized after 96 h for histological analysis. Saline was administered to mice in the control group. RESULTS: Blood tests show elevated serum creatinine, urea nitrogen, and neutrophil gelatinase-associated lipocalin levels in rhabdomyolysis. Loss of tubular epithelial cell nuclei and destruction of the tubular luminal surface structure was observed in the untreated group, which improved with rAT treatment. Immunostaining for Ki-67 showed increased Ki-67-positive nuclei in the tubular epithelial cells in the rAT group, suggesting that rAT may promote tubular epithelial cell regeneration. The microvilli of the brush border of the renal tubules were shed during rhabdomyolysis, and rAT treatment reduced this injury. The vascular endothelial glycocalyx, which is usually impaired by rhabdomyolysis, became functional following rAT treatment. CONCLUSIONS: Treatment with rAT suppressed rhabdomyolysis-induced AKI, suggesting that rAT therapy may be a novel therapeutic approach.

Differences in serum selenoprotein P profile between C57BL/6 and BALB/c mice fed high-fat diet.

BACKGROUND: C57BL/6 mice generally show hyperglycaemia and insulin resistance when fed a high-fat diet (HFD) compared to those of BALB/c mice. However, whether these strains also show different expression profiles of selenoprotein P, a diabetes-related hepatokine, after HFD feeding is unclear. We investigated the effects of HFD on body weight, glucose metabolism, and plasma selenoprotein P levels in C57BL/6 and BALB/c mice. METHODS: Male C57BL/6 and BALB/c mice aged seven weeks were divided into normal diet (ND) and HFD groups. Fasting body weights and blood sugar levels were measured weekly. Blood specimens were collected after 16 h of fasting (in weeks 7, 9, and 11) and after 24 h of subsequent refeeding (in weeks 9 and 11) to analyse plasma selenoprotein P and insulin levels. RESULTS: The mean body weight of the HFD group was consistently higher than that of the ND group for both strains. However, a significant elevation in fasting plasma glucose levels from the early stage was observed only in the HFD group of C57BL/6 mice. In BALB/c mice, a difference in fasting glucose levels between the HFD and ND groups was observed after nine weeks. After seven, nine, and eleven weeks, the fasting plasma insulin levels were higher in the HFD group than in the ND group for both strains. During this period, plasma selenoprotein P levels in the HFD group were significantly higher than those in the ND group of C57BL/6 mice. However, BALB/c mice did not show a significant difference in plasma levels of selenoprotein P between the ND and HFD groups. After refeeding, the plasma insulin and selenoprotein P levels increased compared to those observed during fasting in the ND group for both strains. Elevation of insulin levels, but not of selenoprotein P levels, after refeeding was noticed in the HFD group for both strains. Plasma selenoprotein P level after refeeding was significantly lower than that during fasting in the HFD group of C57BL/6 mice. CONCLUSION: Unlike C57BL/6 mice, BALB/c mice did not show elevated fasting plasma selenoprotein P levels despite HFD feeding. Additionally, the pattern of selenoprotein P levels in the plasma after refeeding differed between C57BL/6 and BALB/c mice. These differences in selenoprotein P expression among strains may be related to different susceptibilities of individuals to diabetes.

Efficacy of combined use of Suvorexant and Ramelteon in preventing postoperative delirium: a retrospective comparative study.

BACKGROUND: Suvorexant and ramelteon have been presented as useful for preventing postoperative delirium. Previous studies reported on the comparison with benzodiazepine hypnotics which have been known for the risk for inducing delirium, but the comparison with patients not taking any hypnotics has not been reported yet. Therefore, we assessed the incidence rates for postoperative delirium comparing cancer patients who received preoperative combined administration with suvorexant and ramelteon and those not taking any hypnotics. METHODS: Among 110 cancer patients who underwent surgeries at the Division of Hepato-Biliary-Pancreatic Surgery at the Shizuoka Cancer Center between April 1, 2017 and June 30, 2020, 50 patients who received combined administration with suvorexant and ramelteon from 7 days prior to their surgeries and 60 patients who did not take any hypnotics including suvorexant and ramelteon were classified. They were retrospectively observed during the 7 days from their surgeries onward to compare the cumulative incidence rates for postoperative delirium. RESULTS: The cumulative incidence rate for postoperative delirium during the 7 days in the combined-administration group was 14.0% (7/50), while that for the no-hypnotic group was 36.7% (22/60), which proved that the incidence rate for the former was significantly low (OR: 0.28, 95%CI: 0.11-0.73, P = 0.009). CONCLUSIONS: The present study suggests that the preventive combined administration with suvorexant and ramelteon starting from the preoperative period for cancer patients can be effective in lowering the incidence rate for postoperative delirium. TRIAL REGISTRATION: Retrospectively registered.

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration.

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

Past Endemic Izumi Fever or Yersinia pseudotuberculosis Infection Which Sporadically Reappears.

Izumi fever (IF), also known as Far East scarlet-like fever (FESLF), is caused by Yersinia pseudotuberculosis and it has clinical features resembling those of Kawasaki disease (KD). As both diseases are rare in adolescents and young adults, it is challenging to recognize them, thus often leading to a delayed diagnosis. We herein present two cases of IF or FESLF (IF/FESLF). The first case was misdiagnosed as KD, which led to a diagnostic delay. The second case was recognized earlier owing to our experience with the first case. Although cultures were negative in both cases, presumably due to the prior use of antimicrobial agents, our clinical suspicion and a paired serological assay for anti-Yersinia pseudotuberculosis antibodies finally led to a successful diagnosis.

FF-10850, a Novel Liposomal Topotecan Achieves Superior Antitumor Activity via Macrophage- and Ammonia-Mediated Payload Release in the Tumor Microenvironment.

Topotecan, an approved treatment for refractory or recurrent ovarian cancer, has clinical limitations such as rapid clearance and hematologic toxicity. To overcome these limitations and maximize clinical benefit, we designed FF-10850, a dihydrosphingomyelin-based liposomal topotecan. FF-10850 demonstrated superior antitumor activity to topotecan in ovarian cancer cell line-based xenograft models, as well as in a clinically relevant DF181 platinum-refractory ovarian cancer patient-derived xenograft model. The safety profile was also improved with mitigation of hematologic toxicity. The improved antitumor activity and safety profile are achieved via its preferential accumulation and payload release triggered in the tumor microenvironment. Our data indicate that tumor-associated macrophages internalize FF-10850, resulting in complete payload release. The release mechanism also appears to be mediated by high ammonia concentration resulting from glutaminolysis, which is activated by tumor metabolic reprogramming. In ammonia-rich conditions, FF-10850 released payload more rapidly and to a greater extent than liposomal doxorubicin, a currently approved treatment for ovarian cancer. FF-10850 significantly enhanced antitumor activity in combination with carboplatin or PARP inhibitor without detrimental effects on body weight in murine xenograft models, and demonstrated synergistic antitumor activity combined with anti-PD-1 antibody with the development of tumor antigen-specific immunity. These results support phase I investigation of FF-10850 for the treatment of solid tumors including ovarian cancer (NCT04047251), and further evaluation in combination settings.

Anesthetic management of a patient with achalasia, a disease with a considerable risk for aspiration under anesthesia.

BACKGROUND: Achalasia is a rare condition characterized by dysfunction of esophageal motility and impaired relaxation of the lower esophageal sphincter. Anesthetic management of these patients is challenging due to the elevated risk of regurgitation and aspiration. CASE PRESENTATION: A 53-year-old man diagnosed with achalasia was scheduled for renal cancer surgery before esophageal myotomy. Since his severe dysphagia suggested the possibility of vomiting and aspiration under anesthesia, a stomach tube was inserted before induction of general anesthesia. After preoxygenation, rapid sequence induction was performed and an antiemetic was administered to prevent postoperative vomiting. Although anesthetic management was uneventful, the inserted stomach tube coiled up in the dilated esophagus and substantial residue was aspirated via the tube even after a prolonged fasting period. CONCLUSION: Anesthesiologists should be familiar with achalasia even though it is an uncommon disease, since affected patients are at risk of regurgitation and aspiration under anesthesia.

Effects of oral function and depressive tendencies on nutritional status in older adults requiring support or low-level care: An investigation using path analysis.

AIM: This study investigated the effects of differences in oral function and depressive tendencies on nutritional status in older adults requiring support or low-level care. METHODS: In 106 older adult participants residing in nursing/care homes or participating in community-level preventive care activities, the Mini Nutritional Assessment-Short Form (MNA®-SF) for nutritional status and oral diadochokinesis (ODK), tongue pressure, and repetitive saliva swallowing test (RSST) for oral function, 15-item Geriatric Depression Scale (GDS), Diet-Related Quality of Life Scale-Short Form (DRQOL-SF), and Functional Independence Measure (FIM) were administered. Basic information, including cognitive function, was evaluated. Hierarchical MNA (dependent variable)-based multiple regression analysis was performed, followed by path analysis using factors with significant associations with MNA scores. RESULTS: RSST, ODK, tongue pressure, FIM, and DRQOL were positively correlated with MNA scores and GDS was negatively correlated. Hierarchical multiple regression demonstrated associations with tongue pressure, GDS, FIM, DRQOL scores, and gender. Path analysis confirmed significant paths from tongue pressure to MNA, tongue pressure to FIM, and FIM to MNA (P < .001). Significant paths were confirmed from GDS to MNA (P < .01), from DRQOL to MNA (P < .05), and from gender to MNA (P < .01). CONCLUSIONS: Tongue pressure, GDS, FIM, DRQOL scores, and gender were identified as factors that directly affect MNA. Tongue pressure showed the greatest effect and indirectly affected MNA via FIM. These findings emphasize the importance of early detection of low nutritional risk for preventing depression and oral function deterioration, and of evaluation of dietary satisfaction and improvement of quality of life in diets.

Exploring the benefits of full-time hospital facility dogs working with nurse handlers in a children's hospital.

OBJECTIVE: To examine the benefits of full-time hospital facility dogs (HFDs) working with qualified nurse handlers for inpatients in a pediatric medical facility. METHODS: A questionnaire survey on the evaluation of HFD activities was conducted in a hospital that had introduced HFDs for the first time in Japan and has been using them for 9 years. Of the 626 full-time medical staff, 431 responded, of which 270 who observed HFD activities were included in the analysis. The Questionnaire contained 20 questions, and nine questions were selected for presentation in this paper because they focused on the situations in which HFD activities were thought to have a strong impact on inpatients. A comparison of the respondents' evaluations for each question was made, and differences in the respondents' attributes (such as profession, length of clinical experience and experience of dog ownership) for those items were examined. RESULTS: The impact of HFDs in terminal care was ranked highest among the respondents. Similarly, HFDs increased patient cooperation for clinical procedures. The responses to these two items did not differ statistically depending on the respondents' attributes. The results imply that patients were more cooperative even for highly invasive examinations and procedures with the support of HFD activities. CONCLUSIONS: Healthcare providers considered that HFDs were useful, especially for providing support during the terminal phase and for gaining patients' cooperation for procedures. The fact that the handler was a nurse and the HFD team worked full-time may have enhanced the effectiveness of the program.

Serum syndecan-1 concentration in hemolysis, elevated liver enzymes, and low platelets syndrome: A case report.

Background: Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome occurs in pregnant and postpartum individuals. We observed serum syndecan-1 (SDC-1) levels, which is a component of the glycocalyx, in a patient with HELLP syndrome from admission to the postpartum period and examined their association as reflecting the pathophysiology related to endothelial injury. Case presentation: A 31-year-old primiparous female patient without a previous medical history at a gestational age of 37 weeks and 6 days was transferred to our hospital the morning after a visit to a previous hospital with headache and nausea. Elevated transaminase, platelet count, and proteinuria were noted. Head magnetic resonance imaging revealed a caudate nucleus hemorrhage and posterior reversible encephalopathy syndrome. After she delivered her newborn through an emergency cesarean section, she was admitted to the intensive care unit. On day 4 post-delivery, the patient's D-dimer concentration was elevated, and contrast-enhanced computed tomography was performed. The results indicated pulmonary embolism, and heparin administration was initiated. The serum SDC-1 level was highest on day 1 post-delivery and quickly decreased subsequently; however, it remained elevated during the postpartum period. Her condition gradually improved, and she was extubated on day 6 and discharged from the ICU on day 7 post-delivery. Conclusion: We measured SDC-1 concentration in a patient with HELLP syndrome and found that the clinical course correlated with SDC-1 levels, indicating that SDC-1 is elevated immediately before and after pregnancy termination in patients with HELLP syndrome. Therefore, SDC-1 fluctuations, combined with the elevation of the D-dimer level, may be a potential marker for the early detection of HELLP syndrome and estimation of the syndrome's severity in the future.

Higher oxytocin concentrations occur in subjects who build affiliative relationships with companion robots.

Building affiliative relationships with others is important for mental health. Recently, robots have been expected to play a role in improving mental health, but there is little scientific evidence as to whether they can build affiliative relationships with humans. To investigate that, we conducted studies combining behavior, physiology and questionnaires for companion robot Owners and Non-Owners. The results reveal that the steady-state concentration of oxytocin, a hormone related to affiliative relationships, was significantly higher in Owners than in Non-Owners. In addition, the Owners showed more behaviors indicative of intimacy than the Non-Owners. These results suggest that humans can build affiliative relationships with robots. Fifteen minutes of contact with the robot decreased the concentration of cortisol in both groups, suggesting that even a brief contact can contribute to improving mental health. Therefore, relationships between humans and robots may be one option to improve mental health and enhance well-being.

Recombinant thrombomodulin may protect cardiac capillary endothelial glycocalyx through promoting Glypican-1 expression under experimental endotoxemia.

Introduction: Myocardial dysfunction occurs in patients with sepsis due to vascular endothelial injury. Recombinant human thrombomodulin (rhTM) attenuates vascular endothelial injuries through endothelial glycocalyx (eGC) protection. Hypothesis: We hypothesized that rhTM attenuates myocardial dysfunction via the inhibition of vascular endothelial injury during sepsis. Methods: Ten-week-old male C57BL6 mice were injected intraperitoneally with 20 mg/kg of lipopolysaccharide (LPS). In rhTM-treated mice, rhTM was injected intraperitoneally at 3 and 24 h after LPS injection. Saline was injected intraperitoneally as control. To assess for eGC injury, intensity score was measured 48 h after the LPS injection. To confirm vascular endothelial injuries, ultrastructural analysis was performed using scanning (SEM) and transmission electron microscopy (TEM). Results: The survival rate of the rhTM group at 48 h after LPS injection was significantly higher than that of the control group (68% vs. 17%, p < 0.05). The serum level of troponin I in the rhTM group was lower than that in the control (2.2 ± 0.4 ng/dL vs 9.4 ± 1.1 ng/dL, p < 0.05). The expression of interleukin-6 (IL-6) was attenuated in the rhTM-treated group than in the control (65.3 ± 15.3 ng/mL vs 226.3 ± 19.4 ng/mL, p < 0.05). The serum concentration of syndecan-1, a marker of glycocalyx damage, was significantly decreased 48 h post-administration of LPS in the rhTM-treated group than in the control group. In ultrastructural analysis using SEM and TEM, eGC peeled off from the surface of the capillary lumen in the control. Conversely, the eGC injury was attenuated in the rhTM group. Gene set enrichment analysis revealed that osteomodulin, osteoglycin proline/arginine-rich end leucine-rich repeat protein, and glypican-1, which are proteoglycans, were preserved by rhTM treatment. Their protein expression was retained in endothelial cells. Conclusion: rhTM attenuates sepsis-induced myocardial dysfunction via eGC protection.

Syndecan-1 as a severity biomarker for patients with trauma.

Tissue injury and hemorrhage induced by trauma lead to degradation of the endothelial glycocalyx, causing syndecan-1 (SDC-1) to be shed into the blood. In this study, we investigated whether serum SDC-1 is useful for evaluating trauma severity in patients. A single-center, retrospective, observational study was conducted at Gifu University Hospital. Patients transported to the emergency room for trauma and subsequently admitted to the intensive care unit from January 2019 to December 2021 were enrolled. A linear regression model was constructed to evaluate the association of serum SDC-1 with injury severity score (ISS) and probability of survival (Ps). A total of 76 trauma patients (54 men and 22 women) were analyzed. ISS was significantly associated with serum SDC-1 level in trauma patients. Among the six body regions defined in the AIS used to calculate the ISS score, "chest" and "abdominal or pelvic contents" were significantly associated with serum SDC-1 level, and "extremities or pelvic girdle" also tended to show an association with serum SDC-1 level. Moreover, increasing serum SDC-1 level was significantly correlated with decreasing Ps. Serum SDC-1 may be a useful biomarker for monitoring the severity of trauma in patients. Further large-scale studies are warranted to verify these results.

Local anesthetic lidocaine induces growth suppression of HeLa cells by decreasing and changing the cellular localization of the proliferation marker Ki-67.

Although surgery is a basic therapy for cancer, it causes inflammation and immunosuppression, often resulting in recurrence and metastasis. Previous studies have suggested that anesthetic management influences the prognosis of cancer surgery patients. Administration of local anesthetics, such as lidocaine, for pain control reportedly improves their clinical outcomes; however, the precise underlying mechanism has not been fully elucidated. The growth of human embryonic kidney (HEK) 293T and cervical cancer HeLa cells was inhibited by lidocaine treatment and these cell lines showed different sensitivities for lidocaine. Ki-67 is a significant prognostic marker of cancer because it is expressed in the nucleus of actively proliferating cells. In lidocaine-treated HeLa cells, Ki-67 was detected not only in the nucleus but also in the cytoplasm. In addition, lidocaine-induced cytoplasmic Ki-67 partly colocalized with the increased ER chaperone, glucose-regulated protein 78, which is crucial for protein folding and maintenance of cellular homeostasis. Furthermore, lidocaine decreased Ki-67 levels and increased the population of HeLa cells in the G0/G1 phase. These results indicate that lidocaine plays a significant role in growth suppression by regulating the expression and distribution of Ki-67.

Clinical characteristics of the severe acute respiratory syndrome coronavirus 2 omicron variant compared with the delta variant: a retrospective case-control study of 318 outpatients from a single sight institute in Japan.

Background: Clinical characteristics, including laboratory parameters, of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant have been limited. Methods: This retrospective case-control study was conducted in a single hospital. Patients with coronavirus disease 2019 (COVID-19) who visited the Asahikawa City Hospital outpatient department as new patients and underwent blood tests were included in this study. We analyzed the data from January 2022 to April 2022 during the Omicron phase and from April 2021 to October 2021 during the Delta phase. Patients who were treated at other hospitals after visiting our hospital were excluded. All blood tests were performed before treatment for COVID-19 was initiated. Demographic information, laboratory data, and clinical courses were extracted from electronic medical records. We matched the two groups by age and comorbidities and compared their characteristics. We also analyzed factors associated with pneumonia in the Omicron phase. Results: A total of 151 Omicron patients and 167 delta patients were analyzed in this study. The mean age, rate of comorbidities, and vaccination were significantly higher in the Omicron group. The number of patients with pneumonia or those requiring oxygen, admissions, or both was significantly lower in the Omicron group. Lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, aspartate aminotransferase (AST), and neutrophil-to-lymphocyte ratio (NLR) levels were significantly lower in the Omicron group. Compared with the mild symptom and pneumonia groups in the Omicron group, older age, higher body mass index (BMI), higher non-vaccination, higher LDH, and higher CRP levels were associated with the pneumonia group. Conclusion: The Omicron variant is associated with a reduction in hospitalization and the risk of pneumonia compared to the delta variant in a real-life clinical setting. In the Omicron variant, the risk of pneumonia is related to high-risk factors, laboratory data such as LDH and CRP levels, and no vaccination.

Acute exacerbation of idiopathic hypereosinophilic syndrome following asymptomatic coronavirus disease 2019: a case report.

BACKGROUND: Previous research has suggested that some autoimmune diseases develop after the occurrence of coronavirus disease 2019. Hypereosinophilic syndrome is a rare disease presenting with idiopathic eosinophilia and multiple organ involvement, including the skin, lungs, gastrointestinal tract, heart, and nervous system. The diagnosis of idiopathic hypereosinophilic syndrome poses a dilemma because clinical manifestation and serum biomarkers are similar to those of eosinophilic granulomatosis with polyangiitis. Only a few cases have been reported where coronavirus disease 2019 may have caused the new onset or exacerbation of eosinophilic granulomatosis with polyangiitis or idiopathic hypereosinophilic syndrome. CASE PRESENTATION: We present the case of a 48-year-old Japanese woman with history of asthma who developed deteriorating symptoms of insidiously developed idiopathic hypereosinophilic syndrome following asymptomatic coronavirus disease 2019. She developed acute-onset back pain, tachycardia, abdominal discomfort, loss of appetite, weight loss, skin rash on the back, and numbness of the extremities 3 days after the quarantine period. Extreme hypereosinophilia with multiple abnormal findings including pulmonary ground-glass opacity lesions and mononeuritis multiplex was consistent with hypereosinophilic syndrome. Normal cellularity with eosinophilic proliferation in the bone marrow and negative FIP1L1-PDGFRA raised the diagnosis of idiopathic hypereosinophilic syndrome. Although the patient tested negative for anti-neutrophilic cytoplasmic antibodies and skin biopsy was negative for vasculitis, eosinophilic granulomatosis with polyangiitis could not be excluded. Since glucocorticoids are a standard therapy for both idiopathic hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis, we initiated glucocorticoids following a multidisciplinary discussion. CONCLUSION: Although the relationship between asymptomatic coronavirus disease 2019 and acute idiopathic hypereosinophilic syndrome exacerbation was uncertain, the chronological order of the symptomatic development suggested a possible link. More clinical cases and population-based studies are needed to determine the potential effect of coronavirus disease 2019 on autoimmune diseases.