Casirivimab-imdevimab neutralizing SARS-CoV-2: post-infusion clinical events and their risk factors.

BACKGROUND: Casirivimab-imdevimab has been developed to neutralize SARS-CoV-2. The global clinical trials in outpatients documented several adverse effects (AE), which mandate caution in Japan where part of patients return home. To investigate post-infusion clinical events and their risk factors, we attempted a retrospective study. MAIN BODY: Subjects were a consecutive series of inpatients with COVID-19 undergoing an infusion of casirivimab-imdevimab in our institute. The criteria for administration were in accordance with previous clinical trials, e.g., exclusion of patients necessitating oxygen supply. In Japan, however, SARS-CoV-2 vaccinees were eligible. Methods were review of background factors of status, imaging, and laboratory findings for the outcome of post-infusion events such as temperature increase (Temp+), pulse oximetry below 94%, and other events. Also, we documented the drug efficacy. Of a total of 96 patients with a median follow-up of 54 days, one (1.0%) died who alone was an exception demanding oxygen supply. Other 95 patients (99.0%) recovered from fever and hypoxia by Day 4 and later had no worsening of COVID-19. Median increase of body temperature was 1.0 degrees Celsius, which was used for computation of Temp+. Multivariate analysis showed that for Temp+ (n = 47), white blood cell counts more than 4.3 × 103/microliter (Odds Ratio [OR] 2.593, 95% Confidence Interval [CI] 1.060-6.338, P = 0.037) was at risk, whereas 2-time vaccination for SARS-CoV-2 (OR 0.128, 95% CI 0.026-0.636, P = 0.012) was a preventing factor. Likewise for lowered oximetry (n = 21), CT showing bilateral ground glass attenuation (OR 5.544, CI 1.599-19.228, P = 0.007) was a significant risk factor. Two patients (2.1%) showed bradycardia (asymptomatic, intervention not indicated) on Day 3 and recovery on Day 5. Limitations for this study included the difficulty distinguishing AE from worsening of COVID-19, thus we documented as clinical events. CONCLUSIONS: For 24 h after infusion of casirivimab-imdevimab, COVID-19 patients with increased white blood cell counts may be predisposed to temperature elevation more than 1.0 degrees centigrade, as may bilateral ground glass opacity to lowered oximetry. Thus, patients with leukocytosis and bilateral ground glass attenuation may need precaution for transient fever and hypoxia, respectively.

Efficacy of Emergency Room Skip Strategy in Patients Transferred for Mechanical Thrombectomy.

Objective: Time to recanalization is directly linked to cerebral infarction prognosis. However, patients transferred from another hospital take longer to arrive than those transported directly. To minimize time to recanalization, the emergency room (ER) skip strategy for hospital transfers was executed and reviewed. Methods: From April 2019, patients transferred from another hospital for mechanical thrombectomy were carried into the angio-suite using emergency service stretchers. Results for these patients (ER skip group) were compared with those for patients transported directly to our hospital (Direct group). Results: Among 108 cases in 32 months, 99 patients (91.7%) had major cerebral artery occlusion and underwent endovascular treatment. No differences in age, baseline National Institutes of Health Stroke Scale score, effective recanalization rate, or proportion of posterior circulation cases were seen between groups. The ER skip group (26 patients) showed significantly longer median time from onset to arrival (240 vs. 120 min; p = 0.0001) and significantly shorter median time from arrival to groin puncture (11 vs. 69 min; p = 0.0000). No significant differences were evident in time from groin puncture to recanalization (39 vs. 45 min), time from onset to recanalization (298 vs. 244 min), or rate of modified Rankin Scale score 0-2 after 90 days (42.3% vs. 32.9%). Median time from alarm to recanalization (266 vs. 176 min; p = 0.0001) was significantly longer in the ER skip group. Door-to-puncture (DTP) time for the Direct group gradually fell as the number of cases increased, reaching 40 min by the end of study period. In contrast, DTP time for the ER skip group remained extremely short and did not change further. The proportion of patients who underwent both CT and MRI before endovascular treatment was significantly lower in the Direct group (30.1%) than in the ER skip group (57.7%). In the ER skip group, median length of stay in the primary hospital was 119 min, and the median duration of interhospital transfer was 16 min. Conclusion: The ER skip strategy for patients transferred with large vessel occlusion achieved favorable outcomes comparable to that for direct transport cases. Direct transport to a thrombectomy-capable stroke center remains ideal, however, because the time to intervention is improving for direct transport cases each year.

Mortality related to drug-resistant organisms in surgical sepsis-3: an 8-year time trend study using sequential organ failure assessment scores.

The difference in sequential organ failure assessment (SOFA) scores from the baseline to sepsis is a known predictor of sepsis-3 outcome, but the prognostic value of drug-resistant organisms for mortality is unexplained. We employed sepsis stewardship and herein report an observational study. Study subjects were patients admitted to the Departments of Surgery/Chest Surgery from 2011 through 2018 with a diagnosis of sepsis and a SOFA score of 2 or more. Our sepsis stewardship methods included antimicrobial and diagnostic stewardship and infection control. We determined the primary endpoint as in-hospital death and the secondary endpoint as the annual trend of the risk-adjusted mortality ratio (RAMR). For mortality, we performed logistic regression analysis based on SOFA score, age, sex, comorbid disease, and the presence of methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase inhibitor-producing bacteria. In a total of 457 patients, two factors were significant predictors for fatality, i.e., SOFA score of 9 or more with an odds ratio (OR) 4.921 and 95% confidence interval [95% CI] 1.968-12.302 (P = 0.001) and presence of MRSA with an OR 1.83 and 95% CI 1.003-3.338 (P = 0.049). RAMR showed a decrease during the study years (P < 0.05). Early detection of MRSA may help patients survive surgical sepsis-3. Thus, MRSA-oriented diagnosis may play a role in expediting treatment with anti-MRSA antimicrobials.

[Successful Management of Deep Vein Thromboembolism and Pulmonary Embolism by Edoxaban for Long-Term 5-FU-Based Chemotherapy for Colon Cancer-A Case Report].

A woman in her 70s developed deep vein thromboembolism(DVT)and pulmonary embolism(PE)during chemotherapy for advanced transverse colon cancer. After the first treatment with heparin and warfarin, the anticoagulant was changed to edoxaban to reduce the risk of bleeding. She continued receiving chemotherapy for 4 years. We recommend edoxaban as the first choice of anticoagulant for patients with DVT and PE requiring chemotherapy with fluoropyrimidine-based antineoplastic agents.

Interprofessional Antimicrobial Stewardship Influencing Clostridioides difficile Infection: An 8-Year Study Using Antimicrobial Use Density.

PURPOSE: To reduce Clostridioides difficile infection (CDI), we implemented interprofessional antimicrobial, infection control, and diagnostic stewardship (ipAS) conducted by physicians/pharmacists, infection control nurses, and medical technologists, respectively. As a numerical indicator for ipAS, we used antimicrobial use density (AUD) in an 8-year study to validate its efficacy in CDI reduction. PATIENTS AND METHODS: This was an observational study. CDI was defined as stool samples or C. difficile isolates containing toxin A and/or B from a patient with diarrhea occurring three or more times per day. From 2011-2018 at a 10-ward single site the subjects were in-patients with CDI, and the following data were collected: AUDs for 23 antibiotics, and antimicrobial test results. By 2015, we had established ipAS, consisting of culture submission before the administration of broad-spectrum antimicrobials, the promotion of point-of-care testing for diagnosis-based antimicrobials, perioperative prophylactic antibiotics, intervention at positive diagnosis of blood culture, team round for diarrhea, and inspection on contact precautions and disinfection in CDI cases. The study outcomes included annual numbers of CDI patients and blood culture sets. We compared annual AUDs between former (2011-14) and latter (2015-18) periods using Kruskal-Wallis tests and examined the correlation between AUDs and CDI numbers. RESULTS: Of a total 50,970 patients, 1,750 patients underwent C. difficile toxin tests, of whom 171 patients (9.8%) were positive for CDI. Between the former and latter periods, AUDs for flomoxef (11.96 to 2.71 by medians), panipenem/betamipron (0.30 to 0.00), and clindamycin (3.87 to 2.19) significantly decreased (P<0.05) as did numbers of CDIs (26.5 to 10) (P=0.043). The correlation analysis revealed a significant correlation between AUD for flomoxef and CDIs (P=0.004) and the AUD for piperacillin/tazobactam and CDIs (P=0.010) with a positive Pearson r. CONCLUSION: The integrated antimicrobial, diagnostic, and infection control approach used in ipAS may reduce CDIs.

Mesh removal and reconstruction with posterior components separation technique for delayed mesh infection developed 10 years after abdominal incisional hernia repair: a rare case report.

BACKGROUND: Very few literatures can be found reporting cases and treatment strategies of late-onset mesh infection after abdominal incisional hernia reconstruction. Here, we report a rare case of delayed mesh infection developed 10 years after abdominal incisional hernia repair, which was successfully treated by mesh removal and reconstruction with posterior components separation technique. CASE PRESENTATION: A 66-year-old man, who underwent reconstruction of abdominal incisional hernia by retroperitoneal Composix mesh application 10 years prior, developed 12 × 6.0 × 2.5 cm subcutaneous abscess followed by methicillin-resistant Staphylococcus aureus (MRSA)-related mesh infection. The operation was performed excising the abscess wall without damaging peritoneum, and huge intermuscular defect was successfully reconstructed by posterior components separation technique application. CONCLUSIONS: An early decision of excising contaminated mesh would be preferable to extensive conservative treatments when mesh infection is suspected. Components separation technique application can be of great help when designing reconstruction of huge intramuscular defect after removal of infected mesh.

Correlation among sarcopenia, malnutrition and activities of daily living in patients with vertebral compression fractures: a comparison based on admission and discharge parameters evaluating these conditions.

[Purpose] Sarcopenia may be associated with malnutrition in patients with vertebral compression fractures which may affect a patient's functional prognosis. This study investigated the association between sarcopenia, malnutrition, and activities of daily living at the time of hospital discharge in patients with vertebral compression fractures. [Participants and Methods] The study included 36 patients who were hospitalized with vertebral compression fractures. Sarcopenia was assessed by measuring grip strength and calf circumference. The nutritional status was assessed at the time of hospital admission and at discharge using the Mini Nutritional Assessment Short Form screening tool. Activities of daily living were assessed using the Barthel Index. [Results] The prevalence of sarcopenia at the time of admission was 47.2%. The Barthel Index and Mini Nutritional Assessment Short Form scores in patients with sarcopenia at the time of admission were significantly lower at discharge than to those in patients without sarcopenia. Overall, at discharge, weight and calf circumference decreased significantly with a consequent increase in the prevalence of sarcopenia (55.6%). Multivariate analysis showed that the Mini Nutritional Assessment Short Form score, calf circumference loss, and age affected the Barthel Index at discharge. [Conclusion] Patients with vertebral compression fractures often show sarcopenia and malnutrition, which are conditions that may be exacerbated during hospitalization. These conditions can subsequently affect a patient's activities of daily living; thus, nutritional rehabilitation is important in patients with vertebral compression fractures, as demonstrated in this study.

Excretions/secretions from medicinal larvae (Lucilia sericata) inhibit complement activation by two mechanisms.

Larvae of the blowfly Lucilia sericata facilitate wound healing by removing dead tissue and biofilms from non-healing and necrotic wounds. Another beneficial action of larvae and their excretions/secretions (ES) is down-regulation of excessive inflammation. As prolonged complement activation is key to excessive inflammation, the aim of this study was to elucidate the mechanisms underlying the anti-complement activities of ES. Results revealed that heat sensitive serine proteases in ES degrade multiple complement proteins in all steps of the three complement activation pathways. Importantly, C3a and C5a-major activators of inflammation-were also degraded by ES and pretreatment of these factors with ES completely blocked their ability to induce activation of human neutrophils. Pre-exposure of the neutrophils to ES did not affect their responsiveness to C3a/C5a and fMLP, indicating that the receptors for these activators on neutrophils were not affected by ES. Surprisingly, heat and serine protease inhibitor pretreatment did not affect the ability of ES to inhibit C5b-9 complex formation despite degrading complement proteins, indicating a second complement-inhibiting molecule in ES. Heated ES was as effective as intact ES in inhibiting C3 deposition upon activation of the alternative pathway, but was significantly less effective in wells with a classical or lectin pathway-specific coating. Unfortunately, the molecules affecting the complement system could not be identified due to an insufficient database for L. sericata. Together, larval ES inhibit complement activation by two different mechanisms and down-regulate the C3a/C5a-mediated neutrophil activation. This attenuates the inflammatory process, which may facilitate wound healing.

Mobile spinal enterogenous cyst resulting in intermittent paraplegia in a child: case report.

The authors report the case of a mobile spinal enterogenous cyst in a 2-year-old boy, who was admitted to the hospital several times for intermittent paraplegia. Magnetic resonance imaging and CT revealed an isolated cyst in the lumbar spinal canal. The symptoms were caused by transient myelopathy of the conus medullaris and radiculopathy of the cauda equina due to the changing size and location of the cyst. The cyst was surgically extirpated, after which the symptoms resolved. The histopathological diagnosis was enterogenous cyst. The clinical history of intraspinal enterogenous cyst is usually progressive. Mobility and changes in size are rare pathophysiological findings. The authors speculate that the cyst wall did not adhere to the surrounding structures and had ruptured and quickly reformed. Enterogenous cyst should be considered in the differential diagnosis of spinal intradural cysts in children with radiculomyelopathy.

Hydrogen peroxide causes Vibrio vulnificus bacteriolysis accelerated by sulfonyl fluoride compounds.

Induction of bacteriolysis of Vibrio vulnificus cells by 10 mM hydrogen peroxide (H(2)O(2)) was analyzed. All Vibrio species examined, except for Vibrio hollisae, were lysed by 10 mM H(2)O(2). Bacteriophage induction was not the cause of H(2)O(2)-induced bacteriolysis. Autolysis is also known to cause bacteriolysis. VvpS protein is a serine protease of V. vulnificus essential for autolysis. vvpS mutant underwent H(2)O(2)-induced bacteriolysis in the same manner as the wild type. Protease inhibitors including serine protease inhibitors did not inhibit H(2)O(2)-induced bacteriolysis, which means that bacteriolysis is not due to autolysis. Unexpectedly, H(2)O(2)-induced bacteriolysis was accelerated by adding 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) and phenylmethylsulfonyl fluoride which are serine protease inhibitors. The hydroxyl radical was generated by H(2)O(2)-AEBSF interaction. It was considered that H(2)O(2)-induced bacteriolysis was caused by the hydroxyl radical which was generated by Fenton reaction, and possibly mediated by AEBSF. Deferoxamine, an agent chelating ferric ion and Fenton reaction inhibitor, suppressed both H(2)O(2)-induced bacteriolysis and its acceleration by AEBSF. This suggests that both phenomena were Fenton reaction dependent, and hydroxyl radical generated by Fenton reaction caused bacteriolysis of V. vulnificus though the reason for high susceptibility of Vibrio species to hydroxyl radical is not known.

Effect of hyperbaric oxygen on Vibrio vulnificus and murine infection caused by it.

Vibrio vulnificus is a bacterium known to cause fatal necrotizing soft tissue infection in humans. Here, a remarkable therapeutic effect of hyperbaric oxygen (HBO) on V. vulnificus infection provoked by its injection into mouse footpads is described. HBO was shown to be bactericidal to this bacterium in vitro as well as in the infected tissue. The bactericidal activity of HBO was shown to be due to reactive oxygen species (ROS), the efficacy of HBO against V. vulnificus infection being accounted for by the high sensitivity of this bacterium to ROS. Besides being somewhat weak in ROS-inactivating enzyme activities, this bacterium is also unusually sensitive to ultraviolet light and other DNA-damaging agents. It seems likely that the sensitivity of V. vulnificus to HBO is mainly due to its poor ability to repair oxidative damage to DNA. These findings encourage clinical application of HBO against potentially fatal V. vulnificus infection in humans.

Results of treatment of 112 cases of primary CNS lymphoma.

BACKGROUND: Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found. METHODS: One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy. RESULTS: The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS. CONCLUSIONS: A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.

A rare case of invasive ductal carcinoma with hyperprolactinemia.

We report here a rare form of invasive ductal carcinoma composed of a mass protruding from the tip of the nipple in a 43-year-old woman with hyperprolactinemia. She had been amenorrheic for 15 years following an incomplete pituitary adenomectomy for prolactinoma. She presented with a mass on the left nipple that had been growing for 6 months. Morphologically, the mass resembled adenoma of the nipple. Another mass was located in the subareolar region. She underwent mastectomy after invasive ductal carcinoma was diagnosed. Histopathologically, the tumor of the nipple was invasive ductal carcinoma, which had extended intraductally from another invasive ductal carcinoma in the subareolar region, and had infiltrated the epidermis of the nipple (Paget's disease). MR mammography successfully detected the relationship between the tumors. Postoperatively, the plasma prolactin level was abnormally high, while the plasma estradiol level was quite low, although macro-pituitary adenoma was not detected by MRI. The patient was treated with bromocriptine mesilate, in addition to adjuvant chemotherapy for breast cancer, and the plasma prolactin level has since normalized.

Salvage therapy and late neurotoxicity in patients with recurrent primary CNS lymphoma treated with a modified ProMACE-MOPP hybrid regimen.

We report the efficacy of salvage therapy with a modified ProMACE-MOPP combined with radiation in patients with primary central nervous system lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristin, and methotrexate (MTX: 500 mg/m(2)) administered in 21-day cycles. Patients received 20 Gy of whole-brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every four months for two years. Nine patients with CNS relapse were retreated with additional cycles of the ProMACE-MOPP hybrid regimen with a 90% objective response rate. Median complete response (CR) duration was 13.2 months and median survival time (MST) for the nine patients treated after initial relapse was 30 months. One of 17 patients (5.8%) who had less than 20 Gy of whole brain irradiation developed dementia. In contrast, six of seven (85.7%) patients who had more than 30 Gy of whole brain radiotherapy became demented. Maintaining a moderate dose of MTX, while adding chemotherapeutic agents and 20 Gy of whole brain radiation therapy, improved disease control and overall survival and lowered the incidence of delayed neurologic toxicity in patients with PCNSL. Additional treatment with a ProMACE-MOPP hybrid regimen is still effective for relapsed disease.

Modified ProMACE-MOPP hybrid regimen with moderate-dose methotrexate for patients with primary CNS lymphoma.

The object of this study was to assess the estimation of 2- and 5-year overall survival and tumor response and the frequency and severity of treatment morbidity with a modified ProMACE-MOPP hybrid protocol in patients with primary CNS lymphoma (PCNSL). Thirty-two immunocompetent patients were treated with a regimen of pirarubicin, cyclophosphamide, etoposide, vincristine, and methotrexate (500 mg/m(2)) administered in 21-day cycles. Intraventricular 10 mg of methotrexate was given for eight cycles once a week. Patients received 20 Gy of whole brain radiotherapy after three cycles of chemotherapy. A single cycle of chemotherapy was repeated every 4 months for 2 years. Older patients (aged >60) received a reduced dose of chemotherapeutic agents. Eighteen patients were followed up with neuroimaging and neuropsychological assessments for evidence of CNS toxicity. Sixteen patients completed the regimen as planned. The response rate was 87.5% after the initial chemoradiotherapy. The cumulative survival and progression-free survival rates at 5 years were 56 and 31%, respectively. The median survival time was 68 months. The median progression-free survival time was 39 months. Toxicity included grade 3 or 4 leukopenia in 33% of the cycles administered. There were eight grade 3 or 4 pulmonary toxicities. There were three deaths during chemotherapy: one as a result of sepsis and two of pneumonitis. Three patients (25%) experienced delayed neurologic toxicity while on the complete regimen. Maintaining the dose of methotrexate while adding chemotherapeutic agents improved disease control and overall survival in patients with PCNSL, but early toxicity and delayed neurotoxicity are still a risk of this approach.

Spleen-preserving laparoscopic distal pancreatectomy after division of the splenic vessels.

A 37-year-old woman with a history of syncope was hospitalized with a diagnosis of hypoglycemia due to insulinoma. Computed tomography (CT) and magnetic resonance imaging revealed an enhanced solid mass, 1.5 cm in diameter, at the tail of the pancreas. Angiography via the splenic artery revealed a hypervascular mass. Because the tumor was located deep in the pancreatic parenchyma, laparoscopic distal pancreatectomy was performed. The pancreas was exposed by dissecting the greater omentum, and the tumor was located by intraoperative ultrasonography. After division of the splenic artery, the pancreas, main pancreatic duct, and splenic vein were transected with an endoscopic linear stapler. The pancreatic pedicle was divided at the splenic hilum to preserve the spleen. The postoperative course was uneventful except for the appearance of splenic infarction on a CT scan 2 weeks after surgery but without any overt symptoms. Spleen-preserving laparoscopic distal pancreatectomy by division of splenic vessels is a feasible treatment option for benign pancreatic disease.