Effectiveness of pulse methylprednisolone in patients with non-human immunodeficiency virus pneumocystis pneumonia: a multicentre, retrospective registry-based cohort study.

BACKGROUND: A recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP. METHODS: This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500-1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure. RESULTS: The study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (14.2% vs. 15.5%, P = 0.850) and 180-day mortality (33.5% vs. 27.3%, P = 0.516) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure. CONCLUSIONS: After adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.

Association between intrapleural urokinase monotherapy and treatment failure in patients with pleural infection: a retrospective cohort study.

BACKGROUND: Pleural infection, an infection of the pleural space, is frequently treated with antibiotics and thoracic tube drainage. In case of insufficient drainage, an intrapleural fibrinolytic agent is considered before surgical intervention. However, the effectiveness of fibrinolytic monotherapy is still controversial. Therefore, we aimed to examine the association between urokinase monotherapy and treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection underwent chest tube insertion were divided into two groups including patients treated with or without intrapleural instillation of urokinase. The propensity score overlap weighting was used to balance the baseline characteristics between the groups. Treatment failure was defined by the composite primary outcome of in-hospital death and referral for surgery. RESULTS: Among the 94 patients, 67 and 27 patients were in the urokinase and non-urokinase groups, respectively. Urokinase monotherapy improved the composite outcome between the groups (19.4% vs. 48.1%, p = 0.01). After adjusting using propensity score overlap weighting, urokinase monotherapy improved the composite outcome compared to the non-urokinase group (19.0% vs. 59.5%, p = 0.003). CONCLUSIONS: Urokinase monotherapy can be an important nonsurgical treatment option for patients with pleural infection. TRIAL REGISTRATION: The participants were retrospectively registered.

Optical coherence tomography findings in three patients with Werner syndrome.

BACKGROUND: Werner syndrome is a rare, autosomal recessive disorder characterised by premature aging. It is a typical hereditary progeroid syndrome that can be difficult to diagnose owing to its rarity and the similarity of some of its symptoms, such as juvenile cataracts, to other common ophthalmologic conditions. Early onset of bilateral cataracts is currently used as the ophthalmological feature for Werner syndrome; however, ophthalmologists often find performing a detailed examination of the medical history and genetic testing for Werner syndrome at the time of an ophthalmologic consultation challenging. If a unique ocular finding was observed on ocular examinations in cases of juvenile bilateral cataracts, we could consider Werner syndrome as a differential diagnosis.  CASE PRESENTATION: We documented the cases of three patients with Werner syndrome in whom thinning of the retina in the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were observed using optical coherence tomography (OCT). Visual field tests revealed the loss of visual field mainly owing to glaucoma. The thinnig of the choroidal thickness (CT) in three patients was also observed using enhanced depth imaging (EDI)-OCT. CONCLUSIONS: Three patients have thinning of the RNFL, GCC, and choroidal thickness and the loss of visual field. These findings suggest the need for including Werner syndrome in the differential diagnosis when patients presenting with juvenile cataracts of unknown cause also show abnormal retinal and choroidal thinning in the OCT images.

The relationship between chest tube position in the thoracic cavity and treatment failure in patients with pleural infection: a retrospective cohort study.

BACKGROUND: Pleural infection is an infection of the pleural space that is usually treated with antibiotics and source control. Chest tube insertion is the most popular and widely used drainage technique. We typically attempt to place the tube at the bottom of the thoracic cavity to consider the effects of gravity; however, the effectiveness of this practice is not well-defined. Therefore, we aimed to examine whether the position of the tip of the thoracic tube affects treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection who underwent thoracic tube insertion were divided into two groups: those with the tip of the tube positioned below the 10th thoracic vertebra at the level of the diaphragm (lower position group) and those with the tip placed above the 9th thoracic vertebra (upper position group). We compared whether the position of the tube tip affected treatment failure. Stabilized inverse probability treatment weights (SIPTW) were used to balance the baseline characteristics between the groups. Treatment failure showed a composite outcome of hospital death, referral to surgeons for surgery, and additional chest tube insertion. RESULTS: Among the 87 patients, 41 and 46 patients were in the lower and upper groups, respectively. No significant difference was observed in the composite outcomes between the groups (46.3% vs. 54.3%, P = 0.596). There was also no significant difference in the composite outcome between both groups after adjusting for SIPTW (52.3% vs. 68.8%, P = 0.286). CONCLUSIONS: There were no significant differences in the treatment failure in this study addressing pleural infection treatment, in which the drain tip position was stratified by the 9th and 10th thoracic vertebrae. The position of the tip of the thoracic tube may not be important for pleural infection treatment providing that it is in the thoracic cavity. Trial registration The participants were registered retrospectively.

Differential Alterations of Auditory Gamma Oscillatory Responses Between Pre-Onset High-Risk Individuals and First-Episode Schizophrenia.

Alterations in gamma-band auditory steady-state response (ASSR) are the most robust finding of abnormal neural oscillations in patients with first-episode (FES) and chronic schizophrenia. Gamma-band ASSRs may indicate GABAergic interneuron dysfunction. Nevertheless, it is unknown whether abnormal gamma-band ASSRs are present before the onset of psychosis. Subjects were 15 ultra-high-risk (UHR) individuals, 13 FES patients, and 21 healthy control (HC) subjects. We performed electroencephalogram recordings and measured ASSRs in each group as they were presented with click trains at 20, 30, and 40 Hz. We then conducted time-frequency analyses and calculated intertrial phase coherence and event-related spectral perturbation. The time course of gamma-band ASSRs showed significantly different features among groups. Compared with the HC group, the UHR group was characterized by intact early-latency (0-100 ms) and reduced late-latency (300-500 ms) ASSRs. In contrast, both early- and late-latency ASSRs were significantly reduced in the FES group. Gamma-band ASSRs were correlated with clinical symptoms and attentional functioning in FES (|rs| > 0.70). These results suggest differential alterations of gamma-band ASSRs between UHR and FES groups. The late-latency ASSR alteration may represent a biomarker for early detection of psychosis, while the early-latency ASSR abnormality may develop through the onset of psychosis.

Intact neural activity during a Go/No-go task is associated with high global functioning in schizophrenia.

AIM: Go/No-go derived event-related potential (ERP) signals have been widely used in schizophrenia research to monitor self-control deficits in this disorder. However, no study to date has associated Go/No-go-related ERP with global functioning. METHODS: Participants consisted of 21 patients with schizophrenia and 22 healthy controls. We used a visual Go/No-go paradigm to measure Go/No-go-related N2/P3 ERP components by means of a 64-electrode cap for electroencephalogram recording. We used the Global Assessment of Functioning to evaluate global functioning and analyzed the correlation between ERP indices and global functioning scores. RESULTS: N2 amplitudes were reduced in patients with schizophrenia, but not influenced by either of the Go/No-go conditions. P3 amplitudes were influenced by the Go/No-go conditions, but not reduced in patients with schizophrenia. Global functioning was correlated with the No-go P3 amplitudes, but not N2 amplitudes, in patients with schizophrenia. CONCLUSION: These results indicate that global functioning is associated with intact neural activity rather than impaired neural activity during Go/No-go response inhibition tasks in patients with schizophrenia.

Gamma-band harmonic responses for beta-band auditory steady-state response are intact in patients with early stage schizophrenia.

Gamma oscillations, thought to arise from the activity of ɣ-aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma-band auditory steady-state responses (ASSRs) are notably reduced in both chronic and early-stage schizophrenia patients. Furthermore, alterations in gamma-band ASSRs have been demonstrated in animal models through translational research. However, the 40-Hz harmonic responses of the 20-Hz ASSR are not as well-characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40-Hz harmonic response to the 20-Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra-high-risk (UHR) for psychosis, 13 patients with first-episode schizophrenia (FES), and 21 healthy controls (HCs). The 40-Hz harmonic responses of the 20-Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40-Hz ASSRs, the 40-Hz harmonic responses of the 20-Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma-band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.

Idiopathic Lymphocytic Pleuritis Responding to Corticosteroid Therapy.

An 83-year-old man presented with chronic dyspnea, and chest X-ray showed bilateral pleural effusion. Right thoracentesis revealed lymphocyte-predominant exudate with no malignancy; bacterial and mycobacterial cultures were negative. Thoracoscopy via the right chest and a biopsy of the same site were performed; these showed lymphoplasmacytic infiltration and fibrosis, ruling out malignancy or tuberculosis. We decided to start corticosteroid therapy for the diagnosis of idiopathic lymphocytic pleuritis (ILP). The patient was discharged after clinical improvement, and steroids were tapered off. An early diagnosis by thoracoscopy and the exclusion of other diseases are important for initiating steroid therapy in patients with ILP.

Left Main Bronchus Obstruction in a Patient with Small-cell Lung Cancer Successfully Treated with Venovenous Extracorporeal Membrane Oxygenation.

Lung cancer can cause fatal central airway obstruction. Rapid airway clearance is necessary in some cases, but ventilator management may be insufficient to maintain oxygenation levels. Venovenous extracorporeal membrane oxygenation (VV-ECMO) may be an effective rescue therapy for respiratory failure, but its efficacy in treating tumor-related airway obstruction is unknown. We herein report a case of central airway obstruction and severe acute respiratory failure due to small-cell lung cancer successfully treated with VV-ECMO, bronchoscopic airway intervention, and chemotherapy. VV-ECMO can be an effective option for the treatment of central airway obstruction with acute respiratory failure due to lung cancer.

Low-Dose vs Conventional-Dose Trimethoprim-Sulfamethoxazole Treatment for Pneumocystis Pneumonia in Patients Not Infected With HIV: A Multicenter, Retrospective Observational Cohort Study.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an effective treatment for Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without HIV infection; however, a high incidence of adverse events has been observed. Low-dose TMP-SMX is a potentially effective treatment with fewer adverse events; however, evidence is limited. RESEARCH QUESTION: What is the efficacy and safety of low-dose TMP-SMX for non-HIV PCP compared with conventional-dose TMP-SMX after adjusting for patient background characteristics? STUDY DESIGN AND METHODS: In this multicenter retrospective cohort study, we included patients diagnosed with non-HIV PCP and treated with TMP-SMX between June 2006 and March 2021 at three institutions. The patients were classified into low-dose (TMP < 12.5 mg/kg/d) and conventional-dose (TMP 12.5-20 mg/kg/d) groups. The primary end point was 30-day mortality, and the secondary end points were 180-day mortality, adverse events grade 3 or higher per the Common Terminology Criteria for Adverse Events v5.0, and initial treatment completion rates. Background characteristics were adjusted using the overlap weighting method with propensity scores. RESULTS: Fifty-five patients in the low-dose group and 81 in the conventional-dose group were evaluated. In the overall cohort, the average age was 70.7 years, and the proportion of women was 55.1%. The average dose of TMP-SMX was 8.71 mg/kg/d in the low-dose group and 17.78 mg/kg/d in the conventional-dose group. There was no significant difference in 30-day mortality (6.7% vs 18.4%, respectively; P = .080) or 180-day mortality (14.6% vs 26.1%, respectively; P = .141) after adjusting for patient background characteristics. The incidence of adverse events, especially nausea and hyponatremia, was significantly lower in the low-dose group (29.8% vs 59.0%, respectively; P = .005). The initial treatment completion rates were 43.3% and 29.6% in the low-dose and conventional-dose groups (P = .158), respectively. INTERPRETATION: Survival was similar between the low-dose and conventional-dose TMP-SMX groups, and low-dose TMP-SMX was associated with reduced adverse events in patients with non-HIV PCP.

Comparison of the outcomes of Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients treated with and without biologics.

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.

Empyema and bacteremia caused by Parvimonas micra: A case report.

Parvimonas micra is a gram-positive anaerobic coccus (GPAC) that colonizes the oral cavity and gastrointestinal tract. Recent advances in bacterial identification have confirmed the clinical importance of Parvimonas micra. Here, we report a case of empyema with bacteremia caused by Parvimonas micra. We successfully treated the patient with the appropriate antibiotics and drainage. Parvimonas micra can cause respiratory infections, including empyema, which can progress to bacteremia if treatment is delayed. In Parvimonas micra infections, not only the oral cavity but also the entire body must be investigated to clarify the entry mechanism.

Alterations of auditory-evoked gamma oscillations are more pronounced than alterations of spontaneous power of gamma oscillation in early stages of schizophrenia.

Several animal models of schizophrenia and patients with chronic schizophrenia have shown increased spontaneous power of gamma oscillations. However, the most robust alterations of gamma oscillations in patients with schizophrenia are reduced auditory-oscillatory responses. We hypothesized that patients with early-stage schizophrenia would have increased spontaneous power of gamma oscillations and reduced auditory-oscillatory responses. This study included 77 participants, including 27 ultra-high-risk (UHR) individuals, 19 patients with recent-onset schizophrenia (ROS), and 31 healthy controls (HCs). The auditory steady-state response (ASSR) and spontaneous power of gamma oscillations measured as induced power during the ASSR period were calculated using electroencephalography during 40-Hz auditory click-trains. The ASSRs were lower in the UHR and ROS groups than in the HC group, whereas the spontaneous power of gamma oscillations in the UHR and ROS groups did not significantly differ from power in the HC group. Both early-latency (0-100 ms) and late-latency (300-400 ms) ASSRs were significantly reduced and negatively correlated with the spontaneous power of gamma oscillations in the ROS group. In contrast, UHR individuals exhibited reduced late-latency ASSR and a correlation between the unchanged early-latency ASSR and the spontaneous power of gamma oscillations. ASSR was positively correlated with the hallucinatory behavior score in the ROS group. Correlation patterns between the ASSR and spontaneous power of gamma oscillations differed between the UHR and ROS groups, suggesting that the neural dynamics involved in non-stimulus-locked/task modulation change with disease progression and may be disrupted after psychosis onset.

Generation of Ultralong Liposome Tubes by Membrane Fusion beneath a Laser-Induced Microbubble on Gold Surfaces.

Membrane fusion (MF) is one of the most important and ubiquitous processes in living organisms. In this study, we developed a novel method for MF of liposomes. Our method is based on laser-induced bubble generation on gold surfaces (a plasmonic nanostructure or a flat film). It is a simple and quick process that takes about 1 min. Upon bubble generation, liposomes not only collect and become trapped but also fuse to form long tubes beneath the bubble. Moreover, during laser irradiation, these long tubes remain stable and move with a waving motion while continuing to grow, resulting in the creation of ultralong tubes with lengths of about 50 µm. It should be noted that the morphology of these ultralong tubes is analogous to that of a sea anemone. The behavior of the tubes was also monitored by fluorescence microscopy. The generation of these ultralong tubes is discussed on the basis of Marangoni convection and thermophoresis.

Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study.

This study assessed the immunogenicity and safety of the BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment. We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 ± 1 weeks after the second vaccination. Anti-severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant and Elecsys Anti-SARS-CoV-2 S assays. Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody concentration, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p < .001 on Architect; 4.0 vs 1.2 U/mL, p < .001 on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p = .005 on Architect; 213 vs 573 A/mL, p = .002 on Elecsys). The adjusted odds ratio (aOR) for seroprotection was significantly lower (p < .05) in lung cancer patients than that in non-cancer patients. Analysis of the anticancer treatment types showed that the aOR for seroprotection was significantly lower (p < .05) in lung cancer patients receiving cytotoxic agents. They showed no increase in adverse reactions. BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased (p < .05) antibody titers and showed acceptable safety. Immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

Febrile neutropenia in a patient with non-small-cell lung cancer treated with atezolizumab: A case report.

Hematological immune-related adverse events (hem-irAEs) related to immunotherapy have not been extensively characterized, and there is no report of neutropenia caused by atezolizumab administration. Herein, we report a case of febrile neutropenia caused by a hem-irAEs due to atezolizumab, which was treated with granulocyte-colony stimulating factor (G-CSF) and antibiotic prophylaxis. It is important that oncologists be aware of the hematological toxicities of immune checkpoint inhibitors (ICIs). Furthermore, antibiotics and G-CSF should be administered until absolute neutrophil count recovery in cases of febrile neutropenia complicated by atezolizumab. Systemic corticosteroids should not be administered because they can accentuate the risk of infection.

Combinatrial treatment of anti-High Mobility Group Box-1 monoclonal antibody and epothilone B improves functional recovery after spinal cord contusion injury.

Spinal cord injury (SCI) causes motor and sensory deficits and is currently considered an incurable disease. We have previously reported that administration of anti-High Mobility Group Box-1 monoclonal antibody (anti-HMGB1 mAb) preserved lesion area and improved locomotion recovery in mouse model of SCI. In order to further enhance the recovery, we here examined combinatorial treatment of anti-HMGB1 mAb and epothilone B (Epo B), which has been reported to promote axon regeneration. This combinatorial treatment significantly increased hindlimb movement compared with anti-HMGB1 mAb alone, although Epo B alone failed to increase functional recovery. These results are in agreement with that anti-HMGB1 mAb alone was able to decrease the lesion area spreading and increase the surviving neuron numbers around the lesion, whereas Epo B facilitated axon outgrowth only in combination with anti-HMGB1 mAb, suggesting that anti-HMGB1 mAb-dependent tissue preservation is necessary for Epo B to exhibit its therapeutic effect. Taken together, the combinatorial treatment can be considered as a novel and clinically applicable strategy for SCI.

Simultaneous treatment for M ycobacterium-avium complex lung disease and allergic bronchopulmonary aspergillosis: A case report.

Recently, there are several reports of simultaneous allergic bronchopulmonary aspergillosis (ABPA) and Mycobacterium-avium complex (MAC) lung disease. However, the strategies for early diagnosis and appropriate treatment for patients with both ABPA and MAC lung disease have not been established. Here, we report a case with ABPA complicated by MAC lung disease, which was successfully diagnosed and treated by simultaneous administration of systemic steroids and antimycobacterial drugs. Bronchoscopy can be useful in the diagnosis of such cases. Furthermore, in a patient with concurrent ABPA and MAC lung disease, simultaneous treatments for both diseases could reduce both diseases.

Corticosteroids for hospitalized patients with mild to critically-ill COVID-19: a multicenter, retrospective, propensity score-matched study.

Corticosteroids use in coronavirus disease 2019 (COVID-19) is controversial, especially in mild to severe patients who do not require invasive/noninvasive ventilation. Moreover, many factors remain unclear regarding the appropriate use of corticosteroids for COVID-19. In this context, this multicenter, retrospective, propensity score-matched study was launched to evaluate the efficacy of systemic corticosteroid administration for hospitalized patients with COVID-19 ranging in the degree of severity from mild to critically-ill disease. This multicenter, retrospective study enrolled consecutive hospitalized COVID-19 patients diagnosed January-April 2020 across 30 institutions in Japan. Clinical outcomes were compared for COVID-19 patients who received or did not receive corticosteroids, after adjusting for propensity scores. The primary endpoint was the odds ratio (OR) for improvement on a 7-point ordinal score on Day 15. Of 1092 COVID-19 patients analyzed, 118 patients were assigned to either the corticosteroid and non-corticosteroid group, after propensity score matching. At baseline, most patients did not require invasive/noninvasive ventilation (85.6% corticosteroid group vs. 89.8% non-corticosteroid group). The odds of improvement in a 7-point ordinal score on Day 15 was significantly lower for the corticosteroid versus non-corticosteroid group (OR, 0.611; 95% confidence interval [CI], 0.388-0.962; p = 0.034). The time to improvement in radiological findings was significantly shorter in the corticosteroid versus non-corticosteroid group (hazard ratio [HR], 1.758; 95% CI, 1.323-2.337; p < 0.001), regardless of baseline clinical status. The duration of invasive mechanical ventilation was shorter in corticosteroid versus non-corticosteroid group (HR, 1.466; 95% CI, 0.841-2.554; p = 0.177). Of the 106 patients who received methylprednisolone, the duration of invasive mechanical ventilation was significantly shorter in the pulse/semi-pulse versus standard dose group (HR, 2.831; 95% CI, 1.347-5.950; p = 0.006). In conclusion, corticosteroids for hospitalized patients with COVID-19 did not improve clinical status on Day 15, but reduced the time to improvement in radiological findings for all patients regardless of disease severity and also reduced the duration of invasive mechanical ventilation in patients who required intubation.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry on April 21, 2020 (ID: UMIN000040211).