Validation of the patient State Index for monitoring sedation state in critically ill patients: a prospective observational study.

PURPOSE: The Patient State Index (PSI) is a newly introduced electroencephalogram-based tool for objective and continuous monitoring of sedation levels of patients under general anesthesia. This study investigated the potential correlation between the PSI and the Richmond Agitation‒Sedation Scale (RASS) score in intensive care unit (ICU) patients and established the utility of the PSI in assessing sedation levels. METHODS: In this prospective observational study, PSI values were continuously monitored via SedLine® (Masimo, Irvine, CA, USA); the RASS score was recorded every 2 h for patients on mechanical ventilation. Physicians and nurses were blinded to the PSI values. Overall, 382 PSI and RASS score sets were recorded for 50 patients. RESULTS: The PSI score correlated positively with RASS scores, and Spearman's rank correlation coefficient between the PSI and RASS was 0.79 (95% confidence interval [CI]: 0.75‒0.83). The PSI showed statistically significant difference among the RASS scores (Kruskal‒Wallis chi-square test: 242, df = 6, P < 2.2-e16). The PSI threshold for distinguishing light (RASS score ≥ - 2) sedation from deep sedation (RASS score ≤ - 3) was 54 (95% CI: 50-65; area under the curve, 0.92 [95% CI: 0.89‒0.95]; sensitivity, 0.91 [95% CI: 0.86‒0.95]; specificity, 0.81 [95% CI: 0.77-0.86]). CONCLUSIONS: The PSI correlated positively with RASS scores, which represented a widely used tool for assessing sedation levels, and the values were significantly different among RASS scores. Additionally, the PSI had a high sensitivity and specificity for distinguishing light from deep sedation. The PSI could be useful for assessing sedation levels in ICU patients. University Hospital Medical Information Network (UMIN000035199, December 10, 2018).

Reduced antiviral seropositivity among patients with inflammatory bowel disease treated with immunosuppressive agents.

BACKGROUND: Although live-attenuated vaccines are contraindicated under immunosuppression, the immune status of patients with inflammatory bowel disease (IBD) has not been fully assessed prior to immunosuppressive therapy. AIMS: To investigate antiviral serostatus against viruses requiring live vaccines for prevention in IBD patients undergoing immunosuppressive therapy. METHODS: This multicenter study included IBD patients who were aged <40 years and were treated with thiopurine monotherapy, molecular-targeted monotherapy, or combination therapy. Gender- and age-matched healthy subjects (HS) living in the same areas were included as control group. Antibody titers against measles, rubella, mumps, and varicella were measured by enzyme-linked immunosorbent assays. RESULTS: A total of 437 IBD patients (163 ulcerative colitis [UC] and 274 Crohn's disease [CD]) and 225 HS were included in the final analysis. Compared with HS, IBD patients had lower seropositivity rates for measles (IBD vs. HS = 83.91% vs. 85.33%), rubella (77.55% vs. 84.89%), mumps (37.50% vs. 37.78%), and varicella (91.26% vs. 96.44%). Gender- and age-adjusted seropositivity rates were lower in UC patients than in both CD patients and HS for measles (UC, CD, and HS = 81.60%, 85.29%, and 85.33%), rubella (76.40%, 78.23%, and 84.89%), mumps (27.16%, 43.70%, and 37.78%), and varicella (90.80%, 91.54%, and 96.44%); the difference was significant for all viruses except measles. Divided by the degree of immunosuppression, there were no significant differences in seropositivity rates among IBD patients. CONCLUSIONS: IBD patients, especially those with UC, exhibit reduced seropositivity rates and may benefit from screening prior to the initiation of immunosuppressive therapy.

A Dome-Shaped Aerosol Box for Protection During a Pandemic.

With the rise of COVID-19, the use of aerosol boxes when interacting with COVID-19 patients has increased. However, their use has been controversial. We have been involved in the development of a dome-shaped aerosol containment device with negative pressure (DAWN), an aerosol box that can maintain negative pressure inside at all times. There are two types of DAWN: one is mounted on a bed (bed type) and the other is mounted on a stretcher (stretcher type). Each device has its own characteristics and can be selected depending on the situation. The bed type has enough space inside to allow procedures to be performed easily. The stretcher type can be attached to a stretcher and can maintain negative pressure when the patient is being moved. Due to the negative pressure structure and easy change of nonwoven fabric adopted in both types of DAWN, it is expected to prevent the scattering of aerosol when it is removed, which is a problem of conventional aerosol boxes. DAWN will contribute to reducing the enormous psychological stress of medical personnel who treat infections, and will contribute to reducing aerosol dispersion.

Life-Threatening Complications Related to Delayed Diagnosis of Euglycemic Diabetic Ketoacidosis Associated with Sodium-Glucose Cotransporter-2 Inhibitors: A Report of 2 Cases.

BACKGROUND Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are widely used owing to their effective glycemic control and protective effects against heart and kidney failure. Euglycemic diabetic ketoacidosis (eu-DKA) is a complication of treatment with SGLT2is. Eu-DKA often leads to delayed diagnosis and results in life-threatening complications. We report 2 critical cases of SGLT2i-associated eu-DKA. CASE REPORT Case 1 was 52-year-old woman with unstable angina scheduled for elective coronary artery bypass grafting surgery. Preoperatively, she underwent tooth extraction which led to poor food intake because of pain. Three days before surgery, the patient had SGLT2i-associated eu-DKA and myocardial infraction, requiring percutaneous coronary intervention and peripheral venoarterial extracorporeal membrane oxygenation. The patient had taken SGLT2i until the morning of admission to the intensive care unit. Case 2 was a 76-year-old woman experiencing SGLT2i-associated eu-DKA and sinus arrest, necessitating a temporary pacemaker, followed by elective gastrojejunal bypass surgery. The SGLT2i was discontinued the day before surgery. On day 3 following surgery, the patient's metabolic acidosis improved, and sinus arrest resolved. CONCLUSIONS Precipitating factors of eu-DKA (caloric restriction and surgical stress) and delay in diagnosis because of a lack of evidence of hyperglycemia could contribute to the development and worsening of life-threatening complications. This reiterates the importance of reviewing ongoing medications of patients with diabetes and considering eu-DKA as a differential diagnosis for patients with high anion gap metabolic acidosis to ensure early intervention. SGLT2i-associated DKA likely develops perioperatively; therefore, clinicians should pay attention to the discontinuation period of SGLT2i before any surgical intervention.

A Case of Intussusception Associated with Pneumatosis Cystoides Intestinalis.

Pneumatosis cystoides intestinalis (PCI) is an uncommon disease that generally lacks symptoms and is rarely associated with intussusception. A 29-year-old man visited our hospital for right upper abdominal pain. Computed tomography (CT) scan revealed multiple air-filled cysts along the intestinal wall and a pseudokidney sign in the transverse colon. A gastrographin enema examination showed a so-called crab finger appearance and multiple elevated translucency in the transverse colon. From these findings, the diagnosis of intussusception associated with PCI was made. The enema and manipulative reduction improved the intussusception. Comparing the enema findings before and after the reduction, we thought that mobile cecum could play an important role in the intussusception. Colonoscopy was performed after the reduction and showed multiple elevated lesions in the ascending colon, which were similar to cluster of grapes. The CT scan of the next day revealed no recurrence of the intussusception, and the patient has not had symptoms of recurrence ever since.

Dexmedetomidine sedation during the nighttime reduced the incidence of postoperative atrial fibrillation in cardiovascular surgery patients after tracheal extubation.

BACKGROUND: Dexmedetomidine (Dex) provides sedation and analgesia by acting on central alpha-2 receptors and is suitable for use after extubation because it has little respiratory depression. Considering the sympathoinhibitory and anxiolytic action of Dex, there is the possibility that Dex might reduce the incidence of atrial fibrillation (AF), which is recognized as a common complication after cardiovascular surgery. We investigated whether the postoperative incidence of AF decreased in patients who received Dex only during the nighttime in the intensive care unit (ICU). METHODS: We retrospectively reviewed ICU charts to determine the incidence of AF and associated factors during the 2-day period after tracheal extubation in patients who underwent cardiovascular surgery from November 2009 to November 2010. The patients were divided into a Dex group (n = 16) and a non-Dex group (n = 29). RESULTS: There were no differences in AF risk factors except for diabetes between the two groups. The average rate of Dex administration was 0.3 ± 0.2 µg/kg/h. There were also no differences between the groups in heart rate during the daytime, central venous pressure, body temperature, white blood cell count, serum level of C-reactive protein, catecholamine use, beta-blocker use, and amount of fentanyl. AF developed in one patient in the Dex group (6.3 %) and ten patients in the non-Dex group (34.5 %) during the observation period, and the difference was significant (p = 0.035). None of the risk factors for AF was significantly associated with AF in univariate analysis; however, multivariate logistic regression analysis using age, Dex use, and beta-blocker use, extracted because their p values in univariate analysis were not exceeding 0.15, showed that Dex use was the only factor associated with the development of AF (p = 0.045, odds ratio 9.75 [1.05-90.8]). CONCLUSIONS: The results suggest that adequate sedation with Dex during the nighttime can reduce the incidence of AF in cardiovascular surgery patients after extubation.

Characterization of the ubiquitin-modified proteome regulated by transient forebrain ischemia.

Ubiquitylation is a posttranslational protein modification that modulates various cellular processes of key significance, including protein degradation and DNA damage repair. In animals subjected to transient cerebral ischemia, ubiquitin-conjugated proteins accumulate in Triton-insoluble aggregates. Although this process is widely considered to modulate the fate of postischemic neurons, few attempts have been made to characterize the ubiquitin-modified proteome in these aggregates. We performed proteomics analyses to identify ubiquitylated proteins in postischemic aggregates. Mice were subjected to 10 minutes of forebrain ischemia and 4 hours of reperfusion. The hippocampi were dissected, aggregates were isolated, and trypsin-digested after spiking with GG-BSA as internal standard. K-ɛ-GG-containing peptides were immunoprecipitated and analyzed by label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. We identified 1,664 peptides to 520 proteins containing at least one K-ɛ-GG. Sixty-six proteins were highly ubiquitylated, with 10 or more K-ɛ-GG peptides. Based on selection criteria of greater than fivefold increase and P<0.001, 763 peptides to 272 proteins were highly enriched in postischemic aggregates. These included proteins involved in important neuronal functions and signaling pathways that are impaired after ischemia. Results of this study could serve as an important platform to uncover the mechanisms linking insoluble ubiquitin aggregates to the functions of postischemic neurons.

A case report of segmental arterial mediolysis in which computed tomography angiography was useful for diagnosis.

A 48-year-old male presented to our hospital with abdominal pain. Laboratory studies showed no abnormality, the severity of his abdominal pain decreased, and the patient was discharged. Five days later, the patient visited a neighborhood clinic because of fever with a 3-day history of temperatures of approximately 38 °C. The patient was admitted to our hospital 6 days after his initial visit. Laboratory investigation revealed a C-reactive protein level of 18.2 mg/dL. Abdominal computed tomography (CT) showed an 80 × 60 mm hematoma behind the descending colon, but no extravasation was detected. Thin-slice maximum-intensity-projection images from CT angiography (CTA) showed irregular narrowing and intermittent fusiform dilatations of the left colonic artery, suggesting a vascular disease, such as segmental arterial mediolysis (SAM). Digital subtraction angiography showed local irregularity, and 'beading and narrowing' of the left colonic artery, similar to the findings on CTA. Left hemicolectomy was electively performed on the twenty-fifth hospital day. Histological findings were consistent with SAM. Thus, CTA was a useful modality for the early diagnosis of SAM.

[A case of calcineurin-inhibitor induced pain syndrome associated with tacrolimus therapy for ulcerative colitis].

A 23-year-old woman was admitted with a relapse of ulcerative colitis. Tacrolimus therapy was initiated following inadequate response to corticosteroid therapy. Although the symptoms partially improved, she suddenly developed severe pain localized to the lower limbs on day 16 of tacrolimus therapy. By day 17, she was unable to move. Magnetic resonance imaging revealed born marrow edema in the lower limbs. We suspected calcineurin-inhibitor induced pain syndrome (CIPS) due to tacrolimus therapy. The pain improved within approximately four weeks of tacrolimus cessation. CIPS that is not associated with organ transplantation is a rare occurrence. Here we report a rare case of CIPS that was caused by tacrolimus therapy in a patient with ulcerative colitis.

[A case of ascending colon neuroendocrine carcinoma drained through a fistula of the descending part of the duodenum].

A 70-year-old woman was admitted for investigation of an abdominal tumor. Abdominal CT revealed an ascending colonic mass measuring 10 × 10 cm, with evidence of liver and lung metastasis. Colonoscopy revealed a cancerous lesion with a central ulcer in the ascending colon. Upper gastrointestinal endoscopy revealed an ulcerative lesion in the descending part of the duodenum. Histologically, the tumor showed features of neuroendocrine carcinoma. The patient died of the primary cancer two and a half months after admission. Autopsy revealed a fistula connecting the ascending colonic mass with the ulcerative lesion in the duodenum.

Flare up of ulcerative colitis during pregnancy treated by adsorptive granulocyte and monocyte apheresis: therapeutic outcomes in three pregnant patients.

PURPOSE: Treatment of ulcerative colitis with drugs during pregnancy potentially may harm the mother and the unborn child. Granulocytapheresis depletes elevated/activated myeloid lineage leucocytes as sources of inflammatory cytokines. We were interested in the safety and efficacy of granulocytapheresis in patients who had ulcerative colitis flare up during pregnancy. METHODS: Three pregnant cases with active ulcerative colitis received Adacolumn granulocytapheresis, up to 10 sessions within 3-6 weeks. Case 1: a 33-year-old woman with left-sided colitis and bloody diarrhoea 7-9 times/day showed loss of mucosal vascular patterns, and contact bleeding from the rectum to the sigmoid colon. Case 2: a 36-year-old woman with pancolitis and bloody diarrhoea 6-8 times/day had loss of mucosal vascular patterns and pus from the rectum to the sigmoid colon. Case 3: a 36-year-old woman with pancolitis and diarrhoea 4-5 times/day (first episode) had erosions and pus in the mucosa from the rectum to the transverse colon. RESULTS: Colitis flare was in weeks 5, 13 and 22 of pregnancy in cases 1, 2, 3, respectively. The corresponding granulocytapheresis sessions were 5, 7, and 10, reflecting an increasing trend with the pregnancy week. Patients 1 and 2 achieved complete remission, patient 3 achieved clinical remission. CONCLUSION: In these three cases with active ulcerative colitis during pregnancy, granulocytapheresis as a non-pharmacologic treatment was effective and safe. In case 3 that did not respond well to the initial granulocytapheresis sessions, a moderate dose of prednisolone enhanced the efficacy of granulocytapheresis and tapering of prednisolone shortly after administration was not associated with relapse.

[Successful treatment of a case of advanced sigmoid colon cancer with occlusion of the common celiacomesenteric trunk].

A 74-year-old man was admitted to our hospital with abdominal pain and bloody stool. The patients' history showed that he had had occlusion of the proximal common trunk of the celiac artery (CA) and the superior mesenteric artery (SMA). The inferior mesenteric artery (IMA), and the marginal artery of the colon had developed well. It was assumed that almost the entire visceral blood might be supplied by the IMA to the CA and the SMA. Our investigation revealed that the patient had advanced cancer of the sigmoid colon, which had caused intestinal obstruction. Sigmoidectomy was performed with care to avoid injuring the IMA and the marginal arcade artery. Normal hemodynamics were successfully established followed by sigmoidectomy, and cure was obtained in this patient.

Gastric cancer following total proctocolectomy for colon cancer associated with ulcerative colitis.

Here we report a case of advanced gastric cancer seen after total proctocolectomy for an early colon cancer associated with ulcerative colitis (UC). A 42-year-old man, diagnosed with UC at the age of 21, had undergone total proctocolectomy at the age of 38 for an early ascending colon cancer. Three years later the patient developed tarry stools and epigastric discomfort. Laboratory data showed anemia together with elevated serum p53 antibody. Gastric endoscopy showed thickening folds around a lesion in the stomach body. The pathological diagnosis was poorly differentiated adenocarcinoma with signet-ring cell carcinoma. Total gastrectomy was performed and the resected specimens showed a diffuse infiltrating tumor (scirrhous gastric carcinoma), 11 × 15 cm in size, with multiple lymph node metastases. Histopathological examination revealed diffuse infiltration of cancer cells throughout the gastric wall and invasion of the serosa. Results of cytology on abdominal lavage were positive for cancer cells. Likewise, immunohistochemical staining showed gastric mucin phenotype cancer cells positive for p53. In conclusion, it is important to bear in mind that patients with UC, especially chronically active pancolitis, potentially bear the risk of upper gastrointestinal complications.

[A case report of Ewing's sarcoma with a peripheral primitive neuroectodermal tumor (ES/pPNET) in the abdominal cavity].

In this report, we present a rare case of Ewing's sarcoma with a peripheral primitive neuroectodermal tumor (ES/pPNET) arising from the abdominal cavity in a 20-year-old woman. The patient complained of upper abdominal pain. Radiological imaging showed a 15-cm mass penetrating to the proxymal jejunum in the upper abdominal cavity and peritoneal disseminations. Immunohistochemical studies revealed that the tumor was ES/pPNET. Although the patient underwent radiation therapy, she died of the disease two months after diagnosis. ES/pPNET in the abdominal cavity is extremely rare and our case showed aggressive behavior and an unfortunate outcome.

Gastrointestinal polyposis with esophageal polyposis is useful for early diagnosis of Cowden's disease.

Cowden's disease, one of the several hamartoma syndromes, is characterized by hyperplastic lesions and hamartomas distributed in the whole body. About thirty percent of patients with Cowden's disease have been reported to be complicated by malignant tumors. Based on the criteria of the International Cowden Consortium, this disease is mainly diagnosed as trichilemmoma of the face and oral mucosal papillomatosis. However, Cowden's disease patients themselves often do not recognize trichilemmoma of the face and oral mucosal papillomatosis. We report a case of Cowden's disease in a 33-year-old female patient who was diagnosed based on the characteristic findings at gastrointestinal endoscopy. Clinically, the patient was aware of having bloody stools. Multiple polyps found endoscopically in the esophagus, stomach, ileum, colon and rectum showed histopathologically hamartomatous changes and epithelial hyperplasia. Physical examination revealed oral papillomatosis and facial trichilemmomas. A germline mutation in exon 8 of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene was found in this case. It was a point mutation of C to T at codon 1003 (CGA-->TGA, arginine-->stop codon). The characteristic findings on gastrointestinal endoscopy led us to a diagnosis of Cowden's disease. It has been reported that gastrointestinal polyposis with esophageal polyposis is found in about 85.7% of Japanese patients with Cowden's disease. The characteristic findings on gastrointestinal endoscopy can be a useful diagnostic clue to Cowden's disease.

[Airway and respiratory management for anesthesia in the patients with severe motor and intellectual disabilities].

BACKGROUND: For the management of general anesthesia in the patients with severe motor and intellectual disabilities, airway and respiratory disorders are severe and may cause fatal events. We retrospectively examined these risk factors. METHODS: We assessed adverse airway and respiratory events associated with anesthesia from perioperative and anesthetic records of these patients retrospectively. RESULTS: Forty-one cases (31 were for fundoplication, and 10 were for gastrostomy or jejunostomy) were involved. On anesthetic introduction, in 9 cases tracheal intubation was difficult (failed in 1 case). These and other 4 cases had developed pharyngeal and laryngeal edema. Manual ventilation by facemask was successful in all cases. During the postoperative period, pneumonia (5 cases), pleural effusion (1 case), and apnea (2 cases) occurred unexpectedly. CONCLUSIONS: Patients with severe motor and intellectual disabilities belong to the group with high risk for general anesthesia.

Effect of weekend 5-aminosalicylic acid (mesalazine) enema as maintenance therapy for ulcerative colitis: results from a randomized controlled study.

BACKGROUND: 5-aminosalicylic acid (5-ASA) is known to be effective in the treatment of active ulcerative colitis (UC). The aim of the current study was to investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when administered twice weekly as a weekend treatment regimen, compared to daily oral 5-ASA alone. We hypothesized that the weekend enema therapy would be better tolerated by patients who worked or attended school. METHODS: Between January 2004 and August 2005, patients with UC, in whom remission of the condition had just been induced, were randomly assigned to either: the weekend 5-ASA enema group (n=11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group (n=13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of the study was defined as the incidence of relapse. The study was stopped after 24 patients had been enrolled because an interim analysis showed a significant benefit of the weekend 5-ASA enema group. RESULTS: In the weekend enema group, 2 patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only group. The multivariate hazard ratio of relapse associated with weekend 5-ASA enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04-0.94). CONCLUSIONS: This study demonstrated the beneficial effects of adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC.

[Treatment outcomes with paclitaxel for advanced gastric cancer patients previously treated with TS-1].

In the present report, we describe the treatment results of paclitaxel in patients with metastatic gastric cancer previously treated with TS-1 or combination chemotherapy of TS-1 and CDDP. Paclitaxel was administered to 4 patients at a weekly dose of 80 mg/m2/day for three weeks followed by a one week interval. Remarkable tumor reduction was observed in 2 patients. Case 1: A 52-year-old male patient with gastric cancer and multiple liver metastases was treated by weekly infusion of paclitaxel as a 2nd line chemotherapy. After 1 course, the tumor was remarkably reduced, and the reduction was judged PR. Case 2: A 31-year-old male patient presented with lymphoangitis carcinomatosa and obstructive jaundice resulting from cancerous lymphoadenopathy. After 1 course, chest radiographs and abdominal CT scan showed remarkable reduction of these lesions. The adverse effects observed with this drug were leucocytopenia and liver dysfunction, both of which improved soon. These results indicate paclitaxel is effective for advanced gastric cancer pretreated with TS-1.

Three-dimensional reconstruction and fractal geometric analysis of serrated adenoma.

Serrated adenoma (SA) is a relatively newly defined entity of colorectal neoplasm first characterized by Longacre and Fenoglio-Preiser in 1990. This lesion is characterized by a complicated serrated edge of crypts. In this study, we performed three-dimensional (3-D) reconstruction, including 3-D distribution patterns of Ki-67-positive cells and fractal dimension of SA, in order to evaluate the nature of the complicated architecture, including its possible morphogenesis. We studied nine colonoscopic polypectomy specimens including three SAs, three tubular adenomas (TAs), and three hyperplastic polyps (HPs). Sixty serial tissue sections per case were stained alternately with hematoxylin and eosin (H&E) and Ki-67 immunostain. Each serial image was then digitized for 3-D computer analysis and the distribution pattern of Ki-67-positive cells was evaluated. Ki-67-immunostained sections were also subjected to 2-D quantitative morphometric study. In addition, the fractal dimensions of images from H&E-stained sections were examined using a box-counting method. Results of the 3-D reconstruction study demonstrated that glandular budding and branching were more frequent in SA than in TA or HP. These findings were confirmed quantitatively by the results of fractal geometric analysis of these polyps (fractal dimension:1.34 +/- 0.08 for SA, 1.23 +/- 0.07 for TA, and 1.28 +/- 0.12 for HP). Ki-67-positive cells in HP were localized mainly in the bottom of crypts and those in TA were diffusely distributed, while Ki-67-positive cells in SA were mainly aggregated in the depressed sites of serrated epithelia. These findings were also confirmed quantitatively using 2-D morphometry. These distribution patterns of the proliferative zone of SA are considered to contribute to the formation of the characteristic serrated epithelia and the complicated morphological appearance of SA.