Obstetric admission to intensive care units in Japan: a cohort study using the Japanese Intensive care PAtient Database.

PURPOSE: This study aimed to describe the epidemiology and annual trends of obstetric patients using a multicenter intensive care database. METHODS: This multicenter, retrospective cohort study used the Japanese Intensive care PAtient Database (JIPAD). We included obstetric patients registered in the JIPAD between 2015 and 2020. We investigated the proportion of obstetric patients among all patients in the intensive care unit (ICU). We also described the characteristics, procedures, and outcomes of obstetric patients. In addition, the annual trends were examined by nonparametric tests for trends. RESULTS: Of the 184,705 patients enrolled in the JIPAD, 750 (0.41%) were obstetric patients from 61 facilities. The median age was 34 years, the number of post-emergency surgeries was 450 (60.0%), and the median APACHE III score was 36. Mechanical ventilation was the most common procedure performed in 247 (32.9%) patients. There were five (0.7%) in-hospital deaths. The proportion of obstetric patients in the ICU did not change between 2015 and 2020 (P for trend = 0.32). However, there was a trend for a significant decrease in the severity of illness and length of hospital stay on an annual basis between 2015 and 2020. Most patients were admitted to the ICU because of a pregnancy-related disorder postoperatively. CONCLUSION: The proportion of obstetric patients was 0.41% of all ICU admissions. The proportion of obstetric patients admitted to the ICU did not change from 2015 to 2020, but the patients' severity of illness and length of hospital stay significantly decreased over time.

Development of a Novel Nutrition-Related Multivariate Biomarker for Mild Cognitive Impairment Based on the Plasma Free Amino Acid Profile.

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632-0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

Decreased circulating branched-chain amino acids are associated with development of Alzheimer's disease in elderly individuals with mild cognitive impairment.

Background: Nutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants. Method: In a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal ("MCI-stable," N = 87) and converted to Alzheimer's disease (AD) ("AD-convert," N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted. Results: Plasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group. Conclusion: The PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status. Clinical trial registration: [https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

[A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after Selection of an Alternative Drug after a Skin Test].

We report our experience of a patient with a history of anaphylactic shock suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor resection. The patient was a 17-year-old female (height : 166 cm, weight : 46 kg). During general anesthesia at another hospital several years ago, she had an anaphylactic shock, and rocuronium was suspected to be the offending drug. To collect information and search for the cause, skin tests were performed for rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and negative for other drugs. At anesthesia induction, we administered vecuronium and confirmed no development of anaphylaxis before commencement of surgery. In the perioperative period, she had no symptoms that indicated anaphylaxis. Since there is potential high cross-reactivity among muscle relaxants, it is important to perform a test for alternative drugs when a muscle relaxant may be a cause of anaphylaxis. Selection and administration of an alternative drug should be carefully performed, even when a skin test is negative for the alternative drug.

[Pressure Ulcer Caused by Long-term Keeping of the Same Body Position during Epidural Labour Analgesia].

We report the case of a 34-year-old woman (height: 153 cm, weight : 62.4 kg, non-pregnant weight : 52 kg, uniparous) without underlying diseases who developed pressure ulcer due to keeping a similar body position during long-term epidural delivery. Induction of childbirth was started in gestational week 40, causing reduction of fetal heart rate, which improved after adoption of a right lateral recumbent position. Severe contractions occurred and epidural labour analgesia was started. The fetal heart rate decreased again and induction of childbirth was suspended, but the right lateral recumbent position was maintained. Epidural administration was continued due to persistent contractions. Next morning, induction of childbirth was restarted and birth occurred in approximately 6 hours. The right lateral recumbent position was maintained for approximately 20 hours. At childbirth, a pressure ulcer was present in the intertrochanteric part of the right femur. The causes included insufficient knowledge of medical staff about the risk of pressure ulcer during epidural delivery, and no position change. A decreased sensation and blocked motor nerve caused by epidural anesthesia might have accelerated pressure ulcer development. This case suggests that preventive measures against pressure ulcer are required in epidural anesthesia in pregnant women.

[Brain abscess due to Fusobacterium necrophorum in a patient with convulsion and no signs of meningitis].

Here, we report brain abscess due to Fusobacterium necrophorum (F. necrophorum) in a 78-year-old healthy man. He developed convulsion and did not have any signs of meningitis. Although the brain magnetic resonance imaging findings of the left occipital lobe were typical of a brain abscess, his cerebrospinal fluid examination revealed only slight pleocytosis and mild increase in protein levels. Thus, it was difficult to rule out the possibility of metastatic brain tumor; the patient's condition was provisionally diagnosed as symptomatic epilepsy secondary to brain abscess. His convulsion disappeared soon after administration of antiepileptic, antibacterial, and steroid agents. A craniotomy was performed to evacuate the abscess, and F. necrophorum was identified by culturing the abscess contents. After the operation, he was treated with appropriate antibacterial agents, which resulted in resolution of the brain abscess. Although Fusobacterium species are gram-negative anaerobic bacilli commensal of the human oropharynx, we need to recognize that Fusobacterium species can be a primary pathogen causing brain abscesses and may leave residual neurological sequelae without early appropriate treatment.

[Difficult airway management in a man with large pharyngeal tumor].

A 58-year-old man (height 164 cm, weight 64 kg) complained of hoarseness one week prior to admission, and breathing difficulty from the previous day. From endoscopic observation, a pedunculated mass below the glottus was oscillating when breathing. Laryngomicrosurgery and tracheotomy were scheduled to remove the pharyngeal tumor. After oxygenation, continuous propofol infusion was carried out. Because mask or LMA ventilation was not possible, a cricothyroid membrane incision kit was inserted and the airway was secured. Laryngomicrosurgery was then performed and after the tumor resections, LMA was inserted and tracheotomy was carried out. In retrospect, a better alternative method would have been to use the cricothyroid membrane incision kit under local anesthesia for airway management.

[A case where the tracheotomy tube was burned during Nd-YAG laser cautery treatment for tracheal neoplasm].

For the treatment of the residual tumor above the incision site, laser cautery was scheduled. Artificial ventilation was carried out using a tracheotomy tube, and a laser fiber was inserted orally for tumor ablation. During the procedure, white smoke appeared in the oral cavity. Considering the damage to the tube, laser use was discontinued and the tube was replaced with a new one. The removed tube had burn marks, but penetration of the tube wall was not observed. Neither respiratory tract burn was found. Prior consultation with technicians regarding the use and settings of the laser appatrates is required.

[Severe arrhythmia after gastrectomy in patients with history of coronary bypass graft surgery using right gastroepiploic artery].

The authors reported two cases of severe arrhythmia after gastrectomy in the patients with history of coronary bypass grafting (CABG) using the right gastroepiploic artery. The first patient was a 64-year-old man who had undergone CABG involving bypassing between the right coronary artery and the right gastroepiploic artery 5 months before. Partial gastrectomy was performed without significant complications. However, he showed severe bradycardia and low output status with anuria in the intensive care unit (ICU). The second patient was a 74-year-old man who had undergone CABG with the identical method 7 years before receiving partial gastrectomy. Although, surgery was performed with intraaortic balloon pumping for his mild heart failure, no other complication was observed during operation and ICU stay. Immediately after being moved to the ward on postoperative day 3, recurrent ventricular tachycardia occurred. Finally, the patient was implanted with an automatic defibrillator.

Daytime hypoxemia, sleep-disordered breathing, and laryngopharyngeal findings in multiple system atrophy.

BACKGROUND: The mechanism underlying nocturnal sudden death in patients with MSA remains unclear. It may be explained by upper airway obstruction, such as vocal cord abductor paralysis; an impairment of the respiratory center, such as Cheyne-Stokes respiration; or an impaired hypoxemic ventilatory response. OBJECTIVE: To investigate the mechanism of sleep-disordered breathing in multiple system atrophy (MSA). DESIGN: We recruited 21 patients with probable MSA who were admitted sequentially to our hospital, and performed daytime blood gas analysis, pulmonary function tests, polysomnography, and fiberoptic laryngoscopy during wakefulness and with the patient under anesthesia. RESULTS: A decrease in arterial oxygen pressure and an increase in alveolar-arterial oxygen gradient significantly correlated with disease duration (P = .045 and .046, respectively). Polysomnography demonstrated Cheyne-Stokes respiration in 3 (15%) of 20 patients. Fiberoptic laryngoscopy during wakefulness showed that 3 (14%) of the 21 patients exhibited vocal cord abductor paralysis, and laryngoscopy under anesthesia showed that 9 (45%) of 20 patients exhibited vocal cord abductor paralysis. Laryngoscopy under anesthesia also revealed that 11 (55%) of 20 patients showed upper airway obstruction in places other than the vocal cords, including obstruction at the base of the tongue or soft palate. In addition, it demonstrated novel laryngopharyngeal findings, such as floppy epiglottis and airway obstruction at the arytenoid. CONCLUSIONS: We observed daytime hypoxemia with an increased alveolar-arterial oxygen gradient, Cheyne-Stokes respiration, and novel abnormal laryngopharyngeal movements in patients with MSA. We also found that laryngoscopy under anesthesia might be useful for evaluating upper airway obstruction. The significance of these findings to the mechanism of sudden death in those with MSA needs to be examined.

[Case of cerebral venous thrombosis due to graves' disease with increased factor VIII activity].

A 39 year-old man was admitted to our hospital because of severe headache with fever continuing over two weeks. Three days after admission he developed aphasia and right hemiparesis, when his CT revealed subarachnoid hemorrhage at the left sylvian fissure. He was diagnosed as suffering from cerebral venous thrombosis because empty delta sign was positive on the enhanced brain CT. Suprasagittal sinus and bilateral transverse sinuses were not detected on the cerebral angiography. He was also diagnosed as having Graves' disease for the first time on the basis of free T3 13.56 pg/ml, free T4 4.65 ng/dl, TSH < 0.01 IU/ml, anti-TSH receptor antibody 4.3 IU/l, and thyroid stimulating antibody 224%. On the examination, homocystine and activities of antithrombin III, protein C, and protein S were normal. Antinculear, anti-DNA, anti-Sm, anticardiolipin beta2GP-I antibodies, and PR3ANCA were negative. Factor VIII activity, however, markedly increased over 300%, which has been known to increase in the cases of hyperthyroidism. He recovered well after the treatment with thiamazole in addition to warfarin followed by intravenous heparin. There are only six cases of cerebral venous thrombosis due to hyperthyroidism with increased factor VIII level. All of those cases were female, and 5 of them were taking oral contraceptives. This is a first Japanese male case.

[A case of dermatomyositis associated with chronic idiopathic myelofibrosis].

A 74-year old woman had been suffering from chronic idiopathic myelofibrosis (CIMF) for three years before noticing skin rash and subsequent muscle weakness. On admission, purplish and erythematous skin rash was seen spreading over large parts of her body, including the face, chest, back and extremities. She could not stand up without assistance due to weakness. On laboratory examination, her hemoglobin was found to be 11.8g/dl, platelet 17,000/microl, WBC 22,500/microl (with blast cells), and CK 1,757 IU/I. Auto-antibodies including antinuclear antibody, Jo-I antibody and rheumatoid factors were negative. Abdominal CT revealed giant splenomegaly. She was diagnosed as having dermatomyositis (DM) associated with CIMF. Although administration of prednisolone followed by methyl-prednisolone pulse therapy ameliorated the weakness and skin rash, WBC increased to 35,000/ microl. In case of worsening of CIMF, azathioprine (AZP) administered. This decreased the WBC count to 13,700/microl and the CK to 49 IU/I 40 days after the administration. Patients with CIMF have an increased incidence of complications of other autoimmune diseases, indicating that the immunological mechanism plays some roles in the progression of the disease. There has been only one other reported case of DM complication. This case suggests usefulness of AZP treatment combined with prednisolone in these patients.

[Successful delivery following subcutaneous heparin administration in a 7-weeks pregnant patient suffering from cerebral venous thrombosis due to secondary protein S deficiency].

A 25-year-old, 7-weeks pregnant woman was admitted to the Nagaoka Red Cross Hospital in a state of confusion, following fever, headache and vomiting. Brain CT and MRI showed swelling in the bilateral thalami, basal ganglia and splenium of corpus callosum, and thrombosis of the internal cerebral veins and straight sinus. Initial treatment by intravenous heparin and glycerol was successful, and she regained her consciousness, leaving antegrade amnesia and childish character change. Her free protein S antigen was 32% (normal 60-127) and subsequently rose to 70% after delivery. She was diagnosed as having secondary protein S deficiency associated with pregnancy. Because warfarin can be teratogenic, subcutaneous heparin injection was prescribed in order to prevent thrombosis and the patient subsequently had a successful delivery. This was the first case in Japanese of successful delivery after subcutaneous heparin treatment in a patient with cerebral venous thrombosis.

Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis.

OBJECTIVE: To elucidate the long-term therapeutic efficacy and safety of low-dose FK506 (tacrolimus) in patients with myasthenia gravis (MG). PATIENTS AND METHODS: We treated nine patients with MG (all women: age range: 35-83 years (mean: 51.1 years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients) with FK506 for more than 24 months (observation period: 24-46 months). All the patients had undergone extended thymectomy before FK506 treatment; two patients (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We evaluated total Quantitative MG (Q-MG) score, anti-acetylcholine receptor (AChR) antibody titer in the blood, interleukin 2 (IL-2) production in peripheral blood mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and adverse effects of FK506. RESULTS: A reduction in steroid dosage of 50% without worsening of the symptoms was observed 1 year after FK506 administration in three out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0-39 points) at 6 months and 1 year after FK506 administration improved by 3 points or more in six (66.7%) and seven (77.8%) out of nine patients, respectively. The efficacy of FK506 was maintained for more than 2 years. Although adverse effects were observed in three patients (33.3%), these were not serious. CONCLUSIONS: Our study indicates that low-dose FK506 treatment may be efficacious not only in controlling intractable myasthenic symptoms, but also in reducing steroid dosage, and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a maximum of 3 years.

[Gadolinium enhancement of the anterior portion of the lumbosacral roots in a case of post-irradiation lumbosacral radiculopathy].

A 35-year-old woman, who underwent the removal of her uterus as a result of treatment for cancer of the cervix, developed weakness in the distal lower limbs after 8 months of subsequent radiation therapy. Although she could not walk because of distal dominant weakness and atrophy in the legs, no sensory disturbances were observed. An MRI scan showed gadolinium enhancement of the anterior portion of the lumbosacral roots in the cauda equina, which corresponded to her neurological symptoms. The administration of corticosteroid and warfarin dramatically alleviated her neurological symptoms, and a follow-up MRI scan one month later demonstrated a marked diminution of the gadolinium enhancement. There were only seven reports describing the abnormalities of the MRI findings, all of which noted the gadolinium enhancement of the anterior portion of the lumbosacral roots. Together with the findings in other reports, the enhancement abnormalities seem to be characteristic of post-irradiation lumbosacral radiculopathy.