Altered thalamic volumes and functional connectivity in the recovered patients with psychosis.

BACKGROUND: Investigating neural correlates in recovered patients with psychosis is important in terms of identifying biological markers associated with recovery status or predicting a possible future relapse. We sought to examine thalamic nuclei volumes and thalamus-centered functional connectivity (FC) in recovered patients with psychosis who discontinued their medication. METHODS: Thirty patients with psychosis who satisfied the criteria for full recovery and 50 healthy controls (HC) matched for age, sex, and education underwent magnetic resonance imaging and clinical evaluation. The recovered patients were divided into the maintained and relapsed subjects according to their clinical status on the follow-ups. Thalamic nuclei volumes and thalamus-centered FC were measured between the recovered patients and HC. Correlations between the thalamic nuclei or altered FC, and clinical symptoms and cognitive functioning were explored. RESULTS: Modest cognitive impairments and reduced thalamic nuclei volumes were evident in the recovered patients. Moreover, we found altered thalamo-cortical connectivity and its associations with negative symptoms and cognitive functioning in the recovered patients compared with HC. CONCLUSION: These findings suggest that there are still cognitive impairments, and aberrant neuronal changes in the recovered patients. The implication of differential FC patterns between the maintained and the relapsed patients remain to be further explored.

Altered functional connectivity in psychotic disorder not otherwise specified.

BACKGROUND: Few studies have investigated functional connectivity (FC) in patients with psychotic disorder not otherwise specified (PNOS). We sought to identify distinct FC differentiating PNOS from schizophrenia (SZ). METHODS: In total, 49 patients with PNOS, 42 with SZ, and 55 healthy controls (HC) matched for age, sex, and education underwent functional magnetic resonance imaging (fMRI) brain scans and clinical evaluation. Using six functional networks consisting of 40 regions of interest (ROIs), we conducted ROI to ROI and intra- and inter-network FC analyses using resting-state fMRI (rs-fMRI) data. Correlations of altered FC with symptomatology were explored. RESULTS: We found common brain connectomics in PNOS and SZ including thalamo-cortical (especially superior temporal gyrus) hyperconnectivity, thalamo-cerebellar hypoconnectivity, and reduced within-thalamic connectivity compared to HC. Additionally, features differentiating the two patient groups included hyperconnectivity between the thalamic subregion and anterior cingulate cortex in PNOS compared to SZ and hyperconnectivity of the thalamic subregions with the posterior cingulate cortex and precentral gyrus in SZ compared to PNOS. CONCLUSIONS: These findings suggest that PNOS and SZ exhibit both common and differentiating changes in neuronal connectivity. Furthermore, they may support the hypothesis that PNOS should be treated as a separate clinical syndrome with distinct neural connectomics.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

In Vitro MIC Values of Rifampin and Ethambutol and Treatment Outcome in Mycobacterium avium Complex Lung Disease.

Although it is known that the in vitro MICs of rifampin and ethambutol are poorly correlated with the clinical response in Mycobacterium avium complex (MAC) lung disease (MAC-LD), evidence for this is limited. This study investigated the association between treatment outcome and the in vitro MICs of rifampin and ethambutol in patients with MAC-LD. Among patients diagnosed with macrolide-susceptible MAC-LD between January 2008 and December 2013, 274 patients who were treated with a standard regimen for ≥12 months until August 2017 and whose in vitro MIC results were available were enrolled at a tertiary referral center in South Korea. The MICs of antimicrobial agents were determined using the broth microdilution method. The mean age of the included patients was 60.4 years. The overall treatment success rate was 79.6% (218/274 patients) and tended to decrease with increasing MICs of rifampin and ethambutol, particularly at MICs of ≥8 µg/ml. Treatment success rate was significantly different between MAC isolates with MICs of ≥8 µg/ml for rifampin and ethambutol and those with MICs of <8 µg/ml for rifampin and/or ethambutol (64.9% versus 85.3%, P < 0.001). Multivariate analysis showed that an MIC of ≥8 µg/ml for both drugs and initial sputum acid-fast bacillus (AFB) smear positivity were independent risk factors for an unfavorable response (adjusted odds ratio [OR] = 3.154, 95% confidence interval [CI] = 1.641 to 6.063, and P = 0.001 for an MIC of ≥8 µg/ml; adjusted OR = 2.769, 95% CI = 1.420 to 5.399, and P = 0.003 for initial sputum AFB smear positivity). These findings suggest that the in vitro MICs of rifampin and ethambutol may be related to treatment outcome in MAC-LD.

A shorter treatment duration may be sufficient for patients with Mycobacterium massiliense lung disease than with Mycobacterium abscessus lung disease.

BACKGROUND: Mycobacterium abscessus complex is the second most common organism isolated from patients with nontuberculous mycobacterial (NTM) lung disease in South Korea. This study aimed to compare clinical features and treatment outcomes of M. abscessus and Mycobacterium massiliense lung disease. METHODS: We retrospectively identified stored clinical isolates of M. abscessus complex as either M. abscessus or M. massiliense and reviewed medical records to compare clinical characteristics and treatment responses. All patients were treated empirically over several months with multidrug regimens, including a macrolide and one or more parenteral agents. RESULTS: Of the 249 patient isolates tested, 128 (59 with M. abscessus and 69 with M. massiliense) met the American Thoracic Society diagnostic criteria for NTM pulmonary disease, and treatment outcomes were analyzed in 48 patients (26 with M. abscessus and 22 with M. massiliense). The clinical and radiologic findings were similar between the two groups. Although the durations of parenteral and total treatment were significantly shorter in patients with M. massiliense than in those with M. abscessus (4.7 months vs 7.4 months, P = .006, and 12.1 months vs 16.3 months, P = .043), the treatment success rate was significantly higher in patients with M. massiliense (95.5%) than in M. abscessus cases (42.3%, P < .001). CONCLUSION: Patients with M. massiliense pulmonary infection responded better to this antibiotic strategy than those with M. abscessus infection. A shortened duration of treatment may be sufficient for M. massiliense pulmonary infection.

Treatment outcomes of refractory MAC pulmonary disease treated with drugs with unclear efficacy.

We aimed to investigate the treatment outcomes of patients with refractory Mycobacterium avium complex (MAC) lung disease treated with regimens containing drugs with unclear efficacy. Of all patients diagnosed with MAC lung disease between April 2004 and September 2012 at a tertiary referral center in South Korea, the outcomes of 51 patients treated with regimens containing drugs with unclear efficacy (clofazimine, moxifloxacin, rifabutin, and linezolid) because of treatment failure after receiving standard treatment were retrospectively analyzed. The mean age (standard deviation) of the 51 patients was 59.0 (10.3) years and 29 (56.9%) were male. The etiologic agent was M. avium in 17 patients (33.3%) and Mycobacterium intracellulare in 34 patients (66.7%); 42 patients (82.4%) had the fibrocavitary form of the disease. Of the 51 patients, 26, 28, 35, and 7 received clofazimine-, moxifloxacin-, rifabutin-, and linezolid-containing regimens (numbers are not mutually exclusive), with median drug administration durations of 147, 128, 209, and 88 days, respectively. Overall, 8 patients (15.7%) had a favorable response. Treatment outcomes did not differ by drug regimen or even by the combination of more than 2 drugs. The treatment outcomes of patients with refractory MAC lung disease were unsatisfactory with regimens containing possibly effective drugs such as clofazimine, moxifloxacin, rifabutin and linezolid.

The efficacy of rifabutin for rifabutin-susceptible, multidrug-resistant tuberculosis.

OBJECTIVE: We investigated the efficacy of rifabutin (RFB)-containing regimens for the treatment of RFB-susceptible, multidrug-resistant tuberculosis (MDR-TB). METHODS: From 146 patients diagnosed with MDR-TB between January 2006 and December 2009 at Asan Medical Center in South Korea, 31 patients (21.2%) were found to have RFB-susceptible MDR-TB. Of these 31 patients, 14 patients who had been treated with RFB for more than one month were included. Forty-two patients with RFB-resistant MDR-TB were selected as a control group, and the outcomes of both groups were retrospectively compared. RESULTS: Of 14 patients with RFB-susceptible MDR-TB, the mean age was 44.4 years and the proportion of extensively drug-resistant TB (XDR-TB) was 35.7% (5/14). Baseline characteristics and the drug resistance pattern (except RFB) did not differ between the two groups. Treatment success was achieved in 12 (85.7%) patients in the RFB group: cure in 10 (71.4%) and treatment completion in two (14.3%). The treatment success rate was 52.4% (22/42) in the control group (p = 0.032). Treatment failure was more common in patients of the control group (40.5% vs. 14.3%; p = 0.106). CONCLUSIONS: RFB is useful as an additional drug in the treatment of MDR-TB in patients with RFB-susceptible MDR-TB.

Induced hypothermia as a new approach to lung rest for the acutely injured lung.

OBJECTIVE: To investigate whether low-frequency ventilation during hypothermia could attenuate lung injury associated with endotoxin and mechanical ventilation. DESIGN: : Experimental animal study. SETTING: University-affiliated animal laboratory. SUBJECTS: Forty-eight Sprague-Dawley rats. INTERVENTIONS: : Lipopolysaccharide was administered to rats intratracheally to induce acute lung injury. After 1 hr of this treatment, animals were assigned to normothermia-only (NO, rectal temperature 37 degrees C, ventilatory frequency 90/min), normothermia-lung rest (NR, 37 degrees C, 45/min), hypothermia-only (HO, 27 degrees C, 90/min), or hypothermia-lung rest (HR, 27 degrees C, 45/min). After 1 hr of injurious ventilation, the lungs of the rats were removed for bronchoalveolar lavage and histologic examination. MEASUREMENTS AND MAIN RESULTS: Compared with the normothermia groups (NO, NR), the neutrophil counts (per milliliter) (NO, 7708 +/- 5704; NR, 10,479 +/- 11,152; HO, 1638 +/- 955; HR, 805 +/- 591) and interleukin-1beta levels (pg/mL) (1180 +/- 439, 1081 +/- 652, 620 +/- 426, 420 +/- 182, respectively) in the bronchoalveolar lavage fluid, the wet-to-dry lung weight ratios (6.0 +/- 0.4, 5.7 +/- 0.4, 5.6 +/- 0.2, 5.2 +/- 0.2, respectively), and histologic acute lung injury scores (8.3 +/- 2.7, 10.4 +/- 3.1, 3.5 +/- 2.1, 3.1 +/- 2.2, respectively) of the hypothermia groups (HO, HR) were lower (all p < .001). Compared with the HO group, the neutrophil counts and protein content (HO, 1367 +/- 490 mug/mL vs. HR, 831 +/- 369 mug/mL) in the bronchoalveolar lavage fluid, the serum lactate dehydrogenase levels (units/mL) (9.1 +/- 3.6 vs. 5.3 +/- 1.5), and the wet-to-dry lung weight ratios of the HR group were lower (all p < .05). CONCLUSIONS: Reduction of ventilatory frequency in conjunction with hypothermia attenuated many variables of acute lung injury in rats. Use of hypothermia could be exploited as a new approach to lung rest for the ventilatory management of the acutely injured lung.