Non-serogroupable Neisseria meningitidis pneumonia in an immunocompetent patient with severe COVID-19 pneumonia: A case report.

Background: Non-serogroupable Neisseria meningitidis (N. meningitidis), the most common type of N. meningitidis in asymptomatic carriers, rarely causes infections. Most reported cases of infection are in patients with immunodeficiency, primarily complement deficiencies. Case presentation: A 54-year-old immunocompetent man was transferred to our hospital to treat severe coronavirus disease 2019 (COVID-19). The patient presented with cough producing a large amount of purulent sputum, which was considered an atypical presentation of COVID-19. Gram staining of the sputum revealed a large number of gram-negative diplococci phagocytosed by many neutrophils, and a diagnosis of bacterial pneumonia was established. The culture yielded non-serogroupable N. meningitidis, and the patient was diagnosed with non-serogroupable N. meningitidis pneumonia. Potential immunodeficiency was considered; however, testing including human immunodeficiency virus and complement factors showed no abnormalities. Conclusions: We report herein a rare case of non-serogroupable N. meningitidis pneumonia that occurred in an immunocompetent patient during the course of severe COVID-19. We consider impaired T cell function attributable to COVID-19 and dexamethasone administration may have triggered a transient immunosuppressive state and led to non-serogroupable N. meningitidis pneumonia.

Animation Deformity: Evaluating the Role of Morphotopologic Features in Suggesting Preventive Surgical Procedures.

BACKGROUND: Animation deformity is an undesirable complication after subpectoral implant reconstruction and is defined as skin distortion during activation of the pectoralis major muscle. However, detailed anatomical features of deformities have yet to be clarified. This study aimed to elucidate how (morphology) and where (topology) animation deformity occurs in reconstructed breasts, and to assess causes and prevention of animation deformity. METHODS: This study included 100 consecutive patients with breast cancer, who underwent unilateral subpectoral implant reconstruction. Animation deformity was evaluated, and the patients were grouped according to both morphologic and topologic features. Univariate and multivariate analyses were performed to identify independent factors associated with deformities. RESULTS: The patients were divided into three groups based on skin distortions with or without implant movement: group I, 60 patients with upper-medial dimpling; group II, 41 patients with upper-lateral folding; and group III, 52 patients with mid-lower lines. Overall, 86 patients (86 percent) showed one or more types of deformity. Among the patients with animation deformity, 24 (28 percent) had implant movement. The authors' study identified axillary dissection as an independent factor for the upper-lateral folding group (OR, 0.30), implant volume for the mid-lower lines group (OR, 1.01), and age for implant movement (OR, 1.06). CONCLUSIONS: Animation deformity was commonly observed in the cohort of patients who underwent subpectoral implant reconstruction and exhibited three morphotopologic patterns of deformity. The current study demonstrated that the morphotopologic grouping of animation deformity may assist in suggesting possible causes and preventive surgical procedures for these deformities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Cardiopulmonary Bypass Surgery in a Patient with Unexpected Heparin-Induced Thrombocytopenia.

We report a case of a 77-year-old woman with massive pulmonary embolism associated with heparin-induced thrombocytopenia. Before developing a pulmonary embolism, the patient underwent gastrectomy due to gastric cancer and received subcutaneous heparin calcium for deep venous thrombosis prophylaxis for 5 d. Then, thrombectomy with cardiopulmonary bypass using full heparinization was successfully performed. The patient was definitively diagnosed with this condition postoperatively, based on elevated serum antibody levels, in addition to pre- and postoperative thrombocytopenia and thrombosis. Intravenous heparin therapy was switched to argatroban. Although it is uncommon, clinicians should consider this condition in patients with a history of heparin exposure.

Allocation of Mechanical Ventilators During a Pandemic: A Mixed-Methods Study of Perceptions Among Japanese Health Care Workers and the General Public.

BACKGROUND: In Japan, public dialogue on allocation of life-saving medical resources remains taboo, and discussion largely has been avoided. RESEARCH QUESTION: Do Japanese health care workers and the general public agree with principles of ventilator allocation developed internationally? STUDY DESIGN AND METHODS: A four-point Likert scale questionnaire was used to assess the extent of agreement or disagreement with internationally developed triage principles for rationing mechanical ventilators during pandemics. Questionnaires were distributed in person or online, and generalized linear models were used to analyze quantitative data. Free-text descriptions were analyzed qualitatively, both deductively and inductively, to compare respondent opinions with those described in previous US studies. RESULTS: Of 3,191 surveys distributed, 1,520 were returned. Allocation of resources to maximize survival from current illness ("save the most lives") was the most popular triage principle, with 95.8% of respondents in agreement. Allocation to ensure a minimum duration of benefit, as determined by predicted prognosis after illness ("ensure minimum duration of benefit"), and allocation to persons who have experienced fewer life stages ("life cycle") obtained agreement of 82.2% and 80.1%, respectively. Withdrawal and reallocation of mechanical ventilators to more appropriate patients was supported by 64.4% of respondents. Only 28.4% of respondents supported the principle of first-come, first-served access to ventilators. INTERPRETATION: Most respondents supported allocation principles developed internationally and disagreed with the idea of first-come, first-served allocation during resource shortages. The Japanese public seems largely to be prepared to discuss the ethical dilemmas and possible solutions regarding fair and transparent allocation of critical care resources as a necessary step in confronting present and future pandemics and disasters.

Validity of an under-mattress sensor for objective sleep measurement in critically ill patients: a prospective observational study.

BACKGROUND: Considering the adverse effects of sleep disturbance in critical care settings, accurate assessment could aid therapy; however, methodological inadequacies mean that no viable option is currently available. Research in healthy population has recently shown that a non-wearable sleep measurement device placed under the mattress of the bed could be beneficial in intensive care settings. Therefore, we aimed to validate this device compared with polysomnography (PSG) and to assess how it related to subjective sleep evaluations. METHODS: This observational study measured the sleep of critically ill adult patients. The primary goal was to validate the Nemuri SCAN (NSCAN; Paramount Bed Co., Ltd., Tokyo, Japan) against the reference standard PSG for 24 h. The secondary goal was to evaluate the association between the objective parameters obtained from NSCAN and PSG and the subjective report data obtained using the Richards-Campbell Sleep Questionnaire (RCSQ) for the nighttime. RESULTS: Eleven participants were evaluated. The median of the total sleep time scored by PSG was 456.0 (353.0-517.5) min during the nighttime and 305.0 (186.2-542.5) min during the daytime. PSG over 24 h revealed significant decreases in restorative sleep, with excessive daytime sleep, but with a normal quantity of nighttime sleep. The agreement, sensitivity, and specificity rates (with 95% confidence intervals) for the NSCAN compared with PSG were 68.4% (67.9-69.0%), 90.1% (89.7-90.6%), and 38.7% (37.9-39.7%), respectively. The median RCSQ value when subjectively evaluating nighttime sleep was 68.0 (26.3-83.5); this showed no correlation with the NSCAN sleep parameters, despite a positive correlation with the ratio of the stage N2 isolated or combined with restorative sleep in the PSG assessment. CONCLUSIONS: NSCAN had moderate agreement, high sensitivity, and poor specificity in intensive care settings, which is most likely due to its inability to identify immobile wakefulness often observed in critically ill patients or sleep depth. This remains a barrier to its use in the assessment of subjective sleep quality. TRIAL REGISTRATION: This investigation was part of an interventional trial registered with the University Hospital Medical Information Network Individual Clinical Trials Registry (UMIN000026350, http://www.umin.ac.jp/icdr/index-j.html) on March 1, 2017.

Off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in a patient with total laryngectomy and a permanent tracheostoma.

Median sternotomy is the standard approach for coronary artery bypass grafting. Herein, we performed off-pump coronary artery bypass grafting via left anterior thoracotomy from the 4th costal space in an unstable angina pectoris patient with total laryngectomy and a permanent tracheostoma. In this patient, median sternotomy had high risks of surgical-site infection and tracheal injury. To avoid these risks, we selected left anterior thoracotomy. Initially, it was difficult to expose the ascending aorta and postdescending branch. With extension of the skin incision to the median area and division of the 5th and 6th ribs and costal arch, we could expose the anastomotic sites, including the ascending aorta and postdescending branch, without median sternotomy conversion. We performed multiple coronary artery bypass graft procedures safely. This approach might be an additional surgical option in patients with total laryngectomy and a permanent tracheostoma.

Physician attire in the intensive care unit in Japan influences visitors' perception of care.

PURPOSE: The objective of this study is to evaluate the impact of physician attire and behavior on perceptions of care by ICU visitors in Japan. MATERIALS AND METHODS: Visitors were surveyed including 117 at a community hospital and 106 at a university hospital. Demographic data (age, gender, relationship to patient, length of stay) were collected. A seven-point Likert scale (1=strongly agree, 4=neutral, 7=strongly disagree) was used to judge physician attire (name tag, white coat, scrubs, short sleeve shirts, blue jeans, sneakers, clogs), behavior (addressing a patient, carrying a snack) and overall effect on perception of care. RESULTS: There are no significant differences (p>0.05) in demographics comparing the two ICUs, except for increased length of stay at the university ICU. Visitors scored the importance of a name tag (median 2, Interquartile Range 1-2), white coat [3,1-4], addressing the patient by last name [2,1-3], wearing scrubs [3,2-4], sneakers [4,3-5], clogs [4,4-5], short sleeves (4,3.5-5), blue jeans [5,4-6], and carrying a snack [6,5-7]. Visitors scored "attire affects perceptions of care" as [3,2-4]. CONCLUSIONS: Physician attire in the ICU affects perceptions of care. Implementation of attire guidelines which require clothing that does not meet visitor preferences should be accompanied by education programs.

Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature.

We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines.

Eventual relapse of tumor growth is commonly observed in head and neck cancer patients, following treatment with platinum-based chemotherapies. This occurrence is believed to be related to the failure to eradicate drug resistant, cancer stem cell (CSC) niches, thereby enriching their population in tumors after treatment. In this study, we show that in contrast to free cisplatin (CDDP), the polymer micelle-based nanomedicine incorporating cisplatin (CDDP/m), can eradicate both the undifferentiated cell and the differentiated cancer cell populations within a head and neck tumor model. Immunohistochemistry of treated tumors showed that opposing to CDDP treatment, CDDP/m could reduce tumor growth without concentrating the CSC-like population. We further showed that CDDP/m, but not CDDP, can localize into hypoxic regions, possibly CSC-rich areas, in the tumors, and can overcome their detoxification mechanism based-on high cellular expression of glutathione to successfully deliver Pt to nuclear DNA. Our data suggests CDDP/m to be a replacement for current platinum therapies, for its ability to eradicate both bulk and CSC-like populations, and in turn to prevent recurrence of tumor growth.

cRGD-installed polymeric micelles loading platinum anticancer drugs enable cooperative treatment against lymph node metastasis.

Lymph node metastasis (LNM) is correlated with decreased survival, indicating high tumor malignancy and being a potential source for subsequent fatal metastases. Targeted therapies inhibiting the formation of LNM, while eliminating established metastatic foci, could provide synergistic effects by reducing the incidence and growth of metastasis. Based on the inhibitory activity of cRGD peptide against the development of metastasis, and the LNM targeting ability of systemically injected drug-loaded polymeric micelles, herein, we studied the capability of cRGD-installed polymeric micelles incorporating the platinum anticancer drug (1,2-diaminocylohexane)platinum(II) (DACHPt) for cooperatively inhibiting the formation and progression of LNM. As cRGD-installed DACHPt-loaded micelles (cRGD-DACHPt/m) presented similar size, drug loading and surface charge to non-conjugated micelles (MeO-DACHPt/m), the differences in the biological performance of the micelles were endorsed to the effect of the ligand. In a syngeneic melanoma model, both MeO-DACHPt/m and cRGD-DACHPt/m showed comparable antitumor activity against the primary tumors and the established metastatic foci in lymph nodes. However, cRGD-DACHPt/m significantly enhanced the efficacy against LNM draining from primary tumors through the effective inhibition of the spreading of cancer cells. This improved inhibition was associated with the ability of cRGD-DACHPt/m to reduce the migration of melanoma cells, which was higher than that of MeO-DACHPt/m, free cRGD and their combination. These results support our strategy of using cRGD-installed micelles for attaining cooperative therapies against LNM exploiting the inhibitory function of the peptide and the cytotoxic effect of the micelles.

Systemic Targeting of Lymph Node Metastasis through the Blood Vascular System by Using Size-Controlled Nanocarriers.

Occult nodal metastases increase the risk of cancer recurrence, demoting prognosis and quality of life of patients. While targeted drug delivery by using systemically administered nanocarriers can potentially control metastatic disease, lymph node metastases have been mainly dealt by locally injecting nanocarriers, which may not always be applicable. Herein, we demonstrated that sub-50 nm polymeric micelles incorporating platinum anticancer drugs could target lymph node metastases in a syngeneic melanoma model after systemic injection, even after removing the primary tumors, limiting the growth of the metastases. By comparing these micelles with clinically used doxorubicin-loaded liposomes (Doxil) having 80 nm, as well as a 70 nm version of the micelles, we found that the targeting efficiency of the nanocarriers against lymph node metastases was associated with their size-regulated abilities to extravasate from the blood vasculature in metastases and to penetrate within the metastatic mass. These findings indicate the potential of sub-50 nm polymeric micelles for developing effective conservative treatments against lymph node metastasis capable of reducing relapse and improving survival.

Ligand-directed targeting of lymphatic vessels uncovers mechanistic insights in melanoma metastasis.

Metastasis is the most lethal step of cancer progression in patients with invasive melanoma. In most human cancers, including melanoma, tumor dissemination through the lymphatic vasculature provides a major route for tumor metastasis. Unfortunately, molecular mechanisms that facilitate interactions between melanoma cells and lymphatic vessels are unknown. Here, we developed an unbiased approach based on molecular mimicry to identify specific receptors that mediate lymphatic endothelial-melanoma cell interactions and metastasis. By screening combinatorial peptide libraries directly on afferent lymphatic vessels resected from melanoma patients during sentinel lymphatic mapping and lymph node biopsies, we identified a significant cohort of melanoma and lymphatic surface binding peptide sequences. The screening approach was designed so that lymphatic endothelium binding peptides mimic cell surface proteins on tumor cells. Therefore, relevant metastasis and lymphatic markers were biochemically identified, and a comprehensive molecular profile of the lymphatic endothelium during melanoma metastasis was generated. Our results identified expression of the phosphatase 2 regulatory subunit A, α-isoform (PPP2R1A) on the cell surfaces of both melanoma cells and lymphatic endothelial cells. Validation experiments showed that PPP2R1A is expressed on the cell surfaces of both melanoma and lymphatic endothelial cells in vitro as well as independent melanoma patient samples. More importantly, PPP2R1A-PPP2R1A homodimers occur at the cellular level to mediate cell-cell interactions at the lymphatic-tumor interface. Our results revealed that PPP2R1A is a new biomarker for melanoma metastasis and show, for the first time to our knowledge, an active interaction between the lymphatic vasculature and melanoma cells during tumor progression.

End-of-life considerations in the ICU in Japan: ethical and legal perspectives.

In Japan, the continuation of critical care at the end of life is a common practice due to the threat of legal action against physicians that may choose a palliative care approach. This is beginning to change due to public debate related to a series of controversial incidents concerning end-of-life care over the last decade. In this review we contrast and compare the history and evolution of end-of-life care in Japan vs. the USA and other Asian countries. Efforts by the Japanese Society of Intensive Care Medicine (JSICM) to establish better end-of-life care systems, as well as future directions in palliative care in Japan, are discussed.

[Case of bilateral subdural empyema complicating Campylobacter fetus subspecies fetus meningitis].

Campylobacter fetus subspecies fetus (C. fetus) is a relatively rare cause of meningitis, with only 3 cases of C. fetus subdural empyema reported to date. We experienced a case of bilateral subdural empyema complicating C. fetus meningitis. A 51-year-old man was found lying unconscious on a street and was brought to the hospital in an ambulance. He had no past history of any underlying disease but he had suffered head trauma approximately 1 month prior to this episode. On admission, he had high fever and developed a convulsion fit. Because the cerebrospinal fluid (CSF) findings showed mononuclear dominant pleocytosis and Gram staining revealed spiral-shaped gram negative bacilli, meningitis caused by C. fetus was suspected. Brain CT preformed on admission did not reveal any obvious abnormality. He was immediately treated with antibiotics effective against C. fetus. His disease was complicated by bilateral subdural empyema; therefore, bilateral burr hole drainage was performed. Durling the operation, a hematoma with an outer membrane and containing yellowish pus was revealed. Infection of a chronic subdural hematoma and consequent formation of subdural empyema was deduced. Eventually, C. fetus was isolated from the CSF arterial blood and subdural empyema. The patient was discharged with no complication after the completion of the treatment.

A quantitative analysis of the acidosis of cardiac arrest: a prospective observational study.

INTRODUCTION: Metabolic acidosis is common in patients with cardiac arrest and is conventionally considered to be essentially due to hyperlactatemia. However, hyperlactatemia alone fails to explain the cause of metabolic acidosis. Recently, the Stewart-Figge methodology has been found to be useful in explaining and quantifying acid-base changes in various clinical situations. This novel quantitative methodology might also provide useful insight into the factors responsible for the acidosis of cardiac arrest. We proposed that hyperlactatemia is not the sole cause of cardiac arrest acidosis and that other factors participate significantly in its development. METHODS: One hundred and five patients with out-of-hospital cardiac arrest and 28 patients with minor injuries (comparison group) who were admitted to the Emergency Department of a tertiary hospital in Tokyo were prospectively included in this study. Serum sodium, potassium, ionized calcium, magnesium, chloride, lactate, albumin, phosphate and blood gases were measured as soon as feasible upon arrival to the emergency department and were later analyzed using the Stewart-Figge methodology. RESULTS: Patients with cardiac arrest had a severe metabolic acidosis (standard base excess -19.1 versus -1.5; P < 0.0001) compared with the control patients. They were also hyperkalemic, hypochloremic, hyperlactatemic and hyperphosphatemic. Anion gap and strong ion gap were also higher in cardiac arrest patients. With the comparison group as a reference, lactate was found to be the strongest determinant of acidosis (-11.8 meq/l), followed by strong ion gap (-7.3 meq/l) and phosphate (-2.9 meq/l). This metabolic acidosis was attenuated by the alkalinizing effect of hypochloremia (+4.6 meq/l), hyperkalemia (+3.6 meq/l) and hypoalbuminemia (+3.5 meq/l). CONCLUSION: The cause of metabolic acidosis in patients with out-of-hospital cardiac arrest is complex and is not due to hyperlactatemia alone. Furthermore, compensating changes occur spontaneously, attenuating its severity.