Size Reduction of the Right Amygdala in Chronic Pain Patients with Emotional Stress: A Systematic Review and Meta-Analysis.

The structural impact of chronic pain on amygdala in chronic pain (CP) patients remains unclear, although major depression and anxiety are known to be associated with its increase and decrease in size, respectively. This study aimed at examining the relationship between emotional stress and amygdala size in CP patients. The effects of mediating and moderating variables were also examined. The PubMed, Embase, and Web of Science databases were searched for English clinical trials from inception to February 2022 using the appropriate keyword strings. We compared the differences in amygdala size assessed with magnetic resonance imaging between CP patients with emotional stress and healthy counterparts. Of the 49 full-text articles identified, 13 studies enrolling 1,551 participants including 738 CP patients with emotional stress and 813 controls were analyzed. Emotional stress evaluated with questionnaires based on Beck depression inventory, Hamilton depression/anxiety scale, state-trait anxiety inventory, and hospital anxiety and depression scale revealed significant differences between CP patients with emotional stress and controls, indicating a subclinical but significant level of emotional stress in CP patients. The results demonstrated an amygdala shrinkage among CP patients with emotional stress compared to the controls, especially the right side (P = .02). Besides, pain from a single body region was more likely to impact the amygdala size compared to diffuse pain (P = .02). Regression analysis revealed no significant association between continuous variables (age, gender, pain duration/intensity) and amygdala size. Our findings demonstrated that emotional stress was associated with a reduced right amygdala size in CP patients.

Teicoplanin versus ß-lactam for febrile patients with Staphylococcus-like bacteremia: focus on methicillin-susceptible Staphylococcus aureus bacteremia.

BACKGROUND: Many studies have shown that vancomycin is inferior to ß-lactam antibiotics in terms of effectiveness in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. However, limited data are available regarding the comparison of clinical outcomes between patients receiving initial teicoplanin and those receiving ß-lactam antibiotics for MSSA bacteremia. METHODS: Eighty-four adults with MSSA bacteremia were included: initial teicoplanin treatment group (n = 28) and ß-lactam treatment group (n = 56). The two groups were further stratified based on propensity score matching according to the outcome analysis using a logistic regression model. We investigated the clinical outcomes between the groups before and after propensity score matching after treatment completion. RESULTS: Pittsburgh bacteremia score ≥ 4 (odds ratio, 60.6; 95%CI, 7.4-496.8) was an independent risk factor for unfavorable outcome. After propensity score matching, the initial teicoplanin treatment group and the ß-lactam treatment group consisted of 28 patients each. No statistically significant differences were observed in the proportions of patients with favorable outcomes and 30-day overall mortality rates between the groups before and after propensity score matching after the completion of teicoplanin or ß-lactam treatment. The Kaplan-Meier 30-day survival curve also showed no significant difference between the patients receiving initial teicoplanin treatment and those receiving ß-lactam treatment before and after matching (hazard ratio, 1.84, 95%CI, 0.60-5.64; and 3.12, 95%CI, 0.98-9.99, respectively). CONCLUSIONS: There were no significant difference in clinical outcomes between initial teicoplanin treatment and ß-lactam treatment among patients with MSSA bacteremia. Pittsburgh bacteremia score ≥ 4 was a significant risk factor for mortality.

Electronic cigarette vapour moderately stimulates pro-inflammatory signalling pathways and interleukin-6 production by human monocyte-derived dendritic cells.

Dendritic cells (DCs) are professional antigen presenting cells that play a critical role in bridging innate and adaptive immunity. Numerous studies have shown that tobacco constituents present in conventional cigarettes affect the phenotype and function of DCs; however, no studies have examined the effects of vapour from E-cigarettes on human DCs. Here, the effects of E-cigarette vapour extract (ECVE) on the phenotype and function of DCs were investigated by creating an in vitro cell culture model using human monocyte-derived DCs (MoDCs). Immature DCs were generated from peripheral blood monocytes and mature DCs were then produced by treatment with LPS or Poly I:C for 24 h. For LPS-matured DCs, 3% ECVE treatment slightly suppressed HLA-DR and CD86 expression, whereas 1% ECVE treatment enhanced IL-6 production. The overall expression of 29 signalling molecules and other cytoplasmic proteins (mainly associated with DC activation) was significantly upregulated in immature DCs by 1% ECVE, and in LPS-treated DCs by 3% ECVE. In particular, the condition that induced IL-6 production also upregulated MAPK pathway activation. These findings indicate that E-cigarette vapour moderately affects human DCs, but the effects are less pronounced than those reported for tobacco smoke.

Impact of biofilm production by Candida species and antifungal therapy on mortality of patients with candidemia.

BACKGROUND AND OBJECTIVES: Few studies have investigated the clinical outcomes of patients with candidemia caused by Candida species with different levels of biofilm formation. We aimed to investigate the impact of antifungal therapy on the outcome of candidemia caused by Candida species that were categorised as low biofilm formers (LBFs), moderate biofilm formers (MBFs), and high biofilm formers (HBFs). METHODS: Adults with candidemia caused by LBF and HBF/MBF Candida species that were susceptible to fluconazole and caspofungin were included to investigate the impact of treatment with fluconazole vs an echinocandin on 30-day crude mortality. RESULTS: In total, 215 patients with candidemia received fluconazole and 116 patients received an echinocandin. In multivariate analysis, Pittsburgh bacteremia score ≥ 4 (adjusted odds ratio [AOR] =2.42; 95% confidence interval [CI], 1.32-4.41), malignancy (AOR = 3.45; 95% CI, 1.83-6.51), not removing the central venous catheter within 48 hours of a positive blood culture (AOR = 4.69; 95% CI, 2.61-8.45), and treatment with fluconazole for candidemia due to HBF/MBF Candida spp. (AOR = 2.23; 95% CI, 1.22-4.06) were independent factors associated with 30-day mortality. Of the 165 patients infected by HBF/MBF Candida isolates, those who received azole therapy had a significantly higher sepsis-related mortality rate than those who received echinocandin therapy (44.9% [49/109] vs 26.8% [15/56], P = .03). CONCLUSIONS: There was a trend of an independent association between fluconazole treatment and poor outcomes in the patients infected by HBF/MBF Candida strains.

Effects of lanthanum carbonate and calcium carbonate on fibroblast growth factor 23 and hepcidin levels in chronic hemodialysis patients.

BACKGROUND: Phosphate binders have an impact on fibroblast growth factor 23 (FGF23); however, the effect of phosphate binders on serum hepcidin has not been explored. We conducted a 24-week multicenter randomized controlled trial to investigate the effects of lanthanum carbonate or calcium carbonate monotherapy on serum phosphate, FGF23, and hepcidin levels in chronic hemodialysis patients. METHODS: Forty-six patients were recruited, and daily dietary phosphorus was controlled between 600-800 mg. Serum calcium, phosphate, albumin, alkaline phosphatase (ALP), FGF23, intact parathyroid hormone (iPTH), hepcidin, high-sensitivity CRP (hsCRP), 25(OH)D, 1,25(OH)2D, fetuin-A, and osteopontin were checked as scheduled. RESULTS: Twenty-five patients completed the study. Mean serum FGF23 level was significantly decreased after a 24-week treatment with lanthanum (8677.5 ± 7490.0 vs. 4692.8 ± 5348.3 pg/mL, p = 0.013, n = 13), but not with calcium (n = 12). The reduction of serum hepcidin in lanthanum group was positively correlated with the decrement of serum phosphate (r = 0.631, p = 0.021) and serum hsCRP (r = 0.670, p = 0.012) levels, respectively. Serum ALP, iPTH, vitamin D, fetuin-A, and osteopontin revealed no significant inter- or intragroup differences. CONCLUSIONS: In summary, a decrease in serum FGF23 levels and a trend of decline in hepcidin levels were observed only in lanthanum group.

Impact of metabolic syndrome and its components on heart rate variability during hemodialysis: a cross-sectional study.

BACKGROUND: Both uremia and metabolic syndrome (MetS) affect heart rate variability (HRV) which is a risk factor of poor prognoses. The aim of this study was to evaluate the impact of MetS on HRV among chronic hemodialysis patients. METHODS: This cross-sectional study was carried out in a teaching hospital in Northern Taiwan from June to August, 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled. HRV were measured for 4 times on the index hemodialysis day (HRV-0, -1, -2, and -3 at before, initial, middle, and late phases of hemodialysis, respectively), and the baseline demographic data and clinical parameters during the hemodialysis session were documented. Then we evaluated the impacts of MetS and its five components on HRV. RESULTS: One hundred and seventy-five patients (100 women, mean age 65.1 ± 12.9 years) were enrolled and included those with MetS (n = 91, 52 %) and without MetS (n = 84, 48 %). The patients with MetS(+) had significantly lower very low frequency, total power, and variance in HRV-0, total power and variance in HRV-2, and variance in HRV-3. (all p ≦ 0.05) When using the individual components of MetS to evaluate the impacts on HRV indices, the fasting plasma glucose (FPG) criterion significantly affected most indices of HRV while other four components including "waist circumference", "triglycerides", "blood pressure", and "high-density lipoprotein" criteria exhibited little impacts on HRV. FPG criterion carried the most powerful influence on cardiac ANS, which was even higher than that of MetS. The HRV of patients with FPG(+) increased initially during the hemodialysis, but turned to decrease dramatically at the late phase of hemodialysis. CONCLUSIONS: The impact of FPG(+) outstood the influence of uremic autonomic dysfunction, and FPG criterion was the most important one among all the components of MetS to influence HRV. These results underscored the importance of interpretation and management for abnormal glucose metabolism.

Heart rate variability is an indicator for intradialytic hypotension among chronic hemodialysis patients.

BACKGROUND: Intradialytic hypotension (IDH) carries adverse impact. Heart rate variability (HRV) represents autonomic cardiac regulation which influences intradialytic blood pressure. We aimed to evaluate the association between IDH and HRV. METHODS: This prospective study was carried out in a teaching hospital in Taiwan from June to August 2010. Adult patients on chronic hemodialysis without active medical conditions were enrolled and received HRV measurements for 4 times (before and during an index hemodialysis session). Patients were categorized by the changes of systolic blood pressure during the index hemodialysis into Group 1 (elevation >20 mmHg), Group 2 (decrease >20 mmHg), and Group 3 (others). Then we compared HRV indices among the three groups, and determined the indicators for IDH. RESULTS: One hundred and seventy-one patients (96 women, mean age 64.9 years) were enrolled and categorized into Group 1 (n = 47, 27.5 %), Group 2 (n = 45, 26.3 %) and Group 3 (n = 79, 46.2 %). Comparing with Group 1 and/or Group 3, Group 2 had significantly higher blood pressure at hemodialysis initiation (most p < 0.001) and statistically lower levels of HRV indices including variance, total power, very low-frequency, low-frequency and high-frequency since the middle phase of the hemodialysis. By logistic regression method, higher systemic blood pressure [odds ratio (OR) 1.048; p < 0.001], heart rate (OR 1.093; p = 0.021), low-frequency/high-frequency ratio (OR 1.715; p = 0.022), as well as lower variance (OR 0.639; p = 0.048) at hemodialysis initiation were independently associated with intradialytic blood pressure changes. CONCLUSIONS: HRV is a useful indicator for IDH among hemodialysis patients.

Surgical Site Infection After Total Knee Arthroplasty: Risk Factors in Patients With Timely Administration of Systemic Prophylactic Antibiotics.

BACKGROUND: Surgical site infection (SSI) after total knee arthroplasty (TKA) is a catastrophic complication. Administration of prophylactic antibiotics within 60 minutes before surgery is a well-established strategy to prevent SSI. The study is aimed to identify the risk factors for SSI regarding primary TKA in patients with timely administration of systemic prophylactic antibiotics. METHODS: A retrospective review of patients with primary TKA between 2009 and 2013 was conducted. Patients who had prophylactic antibiotics administered after skin incision or >60 minutes before skin incision were excluded. RESULTS: Of the 3152 patients enrolled, the incidence of SSI and deep-implant SSI was 1.52% and 0.79%, respectively. Charlson Comorbidity Index ≥3 was an independent risk factor for both SSI (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.24-4.44, P = .01) and deep-implant SSI (OR, 3.46; 95% CI, 1.52-7.91, P < .01). Optimal dose of systemic antibiotics adjusted by patients' body weight for prophylaxis (OR, 0.29; 95% CI, 0.17-0.62, P < .01) and using antibiotic-laden bone cement (OR, 0.33; 95% CI, 0.17-0.64, P < .01) were significant protective factors for SSI. Meanwhile, using antibiotic-laden bone cement (OR, 0.31; 95% CI, 0.13-0.76, P = .01) also significantly decreased the risk of deep-implant SSI. CONCLUSION: Our findings highlight the importance of appropriate dosage of prophylactic antibiotics and use of antibiotic-laden cement in preventing SSI after primary TKA. For prevention of deep-implant SSI, using antibiotic-laden bone cement seems to be an advisable strategy.

Lower Barthel Index Is Associated with Higher Risk of Hospitalization-Requiring Pneumonia in Long-Term Care Facilities.

Pneumonia is an important infectious entity that affects residents in long-term care facilities (LTCFs), whereas hospitalization-requiring pneumonia (HRP) represents a more critical patient condition with worse outcomes. The evidence addressing the association between Barthel index and risk of HRP among LTCF residents is lacking. A multicenter, retrospective cohort study was conducted in three LTCFs enrolling adult patients who resided for 3 months or more and ever underwent Barthel index evaluation within a study period of January 1 to December 31, 2010. The endpoint was HRP after enrollment. A total of 299 patients (169 women; age, 79.0 ± 12.2 years) were enrolled and categorized into HRP Group (n = 68; 36 women; age, 79.1 ± 11.3 years) and Non-HRP Group (n = 231; 133 women; age, 79.0 ± 12.4 years) by the endpoint. The patients in HRP Group had significantly lower Barthel index (8.6 versus 25.8 points, p < 0.001) but higher proportion of chronic obstructive pulmonary disease (13.2% versus 3.9%, p = 0.004). By the multivariate analysis of logistic regression, we found that lower Barthel index (odds ratio (OR), 0.967; p < 0.001), existence of chronic obstructive pulmonary disease (OR, 4.192; p = 0.015), and feeding route (percutaneous endoscopic gastrostomy comparing with oral feeding; OR, 0.177; p = 0.012) were independently associated with HRP. In conclusion, a lower Barthel index is significantly associated with the occurrence of pneumonia that requires hospitalization in long-term care residents. Barthel index is a useful and reliable tool for risk evaluation in this population.

An Engineered Mouse Model That Generates a Diverse Repertoire of Endogenous, High-Affinity Common Light Chain Antibodies.

Bispecific antibodies have gained increasing popularity as therapeutics as they enable novel activities that cannot be achieved with monospecific antibodies. Some of the most popular bispecific formats are molecules in which two Fab arms with different antigen specificities are combined into one IgG-like molecule. One way to produce these bispecific molecules requires the discovery of antibodies against the two antigens of interest that share a common light chain. Here, we present the generation and characterization of a common light chain mouse model, in which the endogenous IGKJ cluster is replaced with a prearranged, modified murine IGKV10-96/IGKJ1 segment. We demonstrate that genetic modification does not impact B-cell development. Upon immunization with ovalbumin, the animals generate an antibody repertoire with VH gene segment usage of a similar diversity to wildtype mice, while the light chain diversity is restricted to antibodies derived from the prearranged IGKV10-96/IGKJ1 germline. We further show that the clonotype diversity of the common light chain immune repertoire matches the diversity of immune repertoire isolated from wildtype mice. Finally, the common light chain anti-ovalbumin antibodies have only slightly lower affinities than antibodies isolated from wildtype mice, demonstrating the suitability of these animals for antibody discovery for bispecific antibody generation.

Feasibility of High-Cellular-Resolution Full-Field, Artificial-Intelligence-Assisted, Real-Time Optical Coherence Tomography in the Evaluation of Vitiligo: A Prospective Longitudinal Follow-Up Study.

Vitiligo, a psychologically distressing pigmentary disorder characterized by white depigmented patches due to melanocyte loss, necessitates non-invasive tools for early detection and treatment response monitoring. High-cellular-resolution full-field optical coherence tomography (CRFF-OCT) is emerging in pigmentary disorder assessment, but its applicability in vitiligo repigmentation after tissue grafting remains unexplored. To investigate the feasibility of CRFF-OCT for evaluating vitiligo lesions following tissue grafting, our investigation involved ten vitiligo patients who underwent suction blister epidermal grafting and laser ablation at a tertiary center between 2021 and 2022. Over a six-month period, clinical features, dermoscopy, and photography data were recorded. Utilizing CRFF-OCT along with artificial intelligence (AI) applications, repigmentation features were captured and analyzed. The CRFF-OCT analysis revealed a distinct dark band in vitiligo lesion skin, indicating melanin loss. Grafted areas exhibited melanocytes with dendrites around the epidermal-dermal junction and hair follicles. CRFF-OCT demonstrated its efficacy in the early detection of melanocyte recovery and accurate melanin quantification. This study introduces CRFF-OCT as a real-time, non-invasive, and in vivo evaluation tool for assessing vitiligo repigmentation, offering valuable insights into pigmentary disorders and treatment responses.

Prognostic factors for critically ill surgical patients with unplanned intensive care unit readmission: Developing a novel predictive scoring model for predicting readmission.

BACKGROUND: Unplanned readmission to the surgical intensive care unit has been demonstrated to worsen patient outcomes. Our objective was to identify risk factors and outcomes associated with unplanned surgical intensive care unit readmission and to develop a predictive scoring model to identify patients at high risk of readmission. METHODS: We retrospectively analyzed patients admitted to the surgical intensive care unit (2020-2021) and categorized them as either with or without unplanned readmission. RESULTS: Of 1,112 patients in the derivation cohort, 76 (6.8%) experienced unplanned surgical intensive care unit readmission, with sepsis being the leading cause of readmission (35.5%). Patients who were readmitted had significantly higher in-hospital mortality rates than those who were not. Multivariate analysis identified congestive heart failure, high Sequential Organ Failure Assessment-Hepatic score, use of carbapenem during surgical intensive care unit stay, as well as factors before surgical intensive care unit discharge such as inadequate glycemic control, positive fluid balance, low partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, and receipt of total parenteral nutrition as independent predictors for unplanned readmission. The scoring model developed using these predictors exhibited good discrimination between readmitted and non-readmitted patients, with an area under the curve of 0.74. The observed rates of unplanned readmission for scores of <4 points and ≥4 points were 4% and 20.2% (P < .001), respectively. The model also demonstrated good performance in the validation cohort, with an area under the curve of 0.74 and 19% observed unplanned readmission rate for scores ≥4 points. CONCLUSION: Besides congestive heart failure, clinicians should meticulously re-evaluate critical variables such as the Sequential Organ Failure Assessment-Hepatic score, partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio, glycemic control, and fluid status before releasing the patient from the surgical intensive care unit. It is crucial to determine the reasons for using carbapenems during surgical intensive care unit stay and the causes for the inability to discontinue total parenteral nutrition before discharging the patient from the surgical intensive care unit.

Risk Factors, Pathogens, and Outcomes of Ventilator-Associated Pneumonia in Non-Cardiac Surgical Patients: A Retrospective Analysis.

Ventilator-associated pneumonia (VAP) is a critical hospital-acquired infection following non-cardiac surgeries, leading to poor outcomes. This study identifies VAP risk factors in non-cardiac surgical patients and determines the causative pathogens. A retrospective analysis with 1:4 propensity-score matching was conducted on patients in a surgical intensive care unit (ICU) from 2010 to 2020 at a private tertiary medical center. Among 99 VAP patients, the mortality rate was 64.7%. VAP risk factors included prolonged mechanical ventilation (odds ratio [OR] 6.435; p < 0.001), repeat intubation (OR 6.438; p < 0.001), lower oxygenation levels upon ICU admission (OR 0.950; p < 0.001), and undergoing gastrointestinal surgery (OR 2.257; p = 0.021). The 30-day mortality risk factors in the VAP group were late-onset VAP (OR 3.450; p = 0.022), inappropriate antibiotic treatment (OR 4.083; p = 0.041), and undergoing gastrointestinal surgeries (OR 4.776; p = 0.019). Nearly half of the Gram-negative infections were resistant strains, and a third were polymicrobial infections. Non-cardiac surgical patients with VAP face adverse hospital outcomes. Identifying high-risk patients and understanding VAP's resistant and microbial nature are crucial for appropriate treatment and improved health outcomes.

The incidence and risk factors of proximal lower extremity deep vein thrombosis without pharmacologic prophylaxis in critically ill surgical Taiwanese patients: A prospective study.

Background: Venous thromboembolism (VTE) in critically ill patients has been well-studied in Western countries. Many studies have developed risk assessments and established pharmacological protocols to prevent deep venous thrombosis (DVT). However, the DVT rate and need for pharmacologic VTE prophylaxis in critically ill Taiwanese patients are limited. This study aimed to prospectively determine the DVT incidence, risk factors, and outcomes in critically ill Taiwanese patients who do not receive pharmacologic VTE prophylaxis. Methods: We conducted a prospective study in a surgical intensive care unit (SICU) of a tertiary academic medical center in Taiwan. Adult patients admitted to SICU from March 2021 to June 2022 received proximal lower extremities DVT surveillance with venous duplex ultrasound. No patient received pharmacologic VTE prophylaxis. The outcomes were the incidence and risk factors of DVT. Results: Among 501 enrolled SICU patients, 21 patients (4.2%) were diagnosed with proximal lower extremities DVT. In a multivariate regression analysis, hypoalbuminemia (odd ratio (OR) = 6.061, 95% confidence interval (CI): 1.067-34.421), femoral central venous catheter (OR = 4.515, 95% CI: 1.547-13.174), ICU stays more than 10 days (OR = 4.017, 95% CI: 1.270-12.707), and swollen leg (OR = 3.427, 95% CI: 1.075-10.930) were independent risk factors for DVT. In addition, patients with proximal lower extremities DVT have more extended ventilator days (p = 0.045) and ICU stays (p = 0.044). Conclusion: Our findings indicate critically ill Taiwanese patients have a higher incidence of DVT than results from prior retrospective studies in the Asian population. Physicians who care for this population should consider the specific risk factors for DVT and prescribe pharmacologic prophylaxis in high-risk groups.

Gram-negative bacterial infections in surgical intensive care unit patients following abdominal surgery: high mortality associated with Stenotrophomonas maltophilia infection.

BACKGROUND: Stenotrophomonas maltophilia, a multidrug-resistant gram-negative bacteria (GNB), is an emerging nosocomial pathogen. This study assessed the clinical outcomes of GNB infections in surgical intensive care unit (SICU) patients post-abdominal surgery, focusing on the differences between S. maltophilia and other GNBs, including Pseudomonas aeruginosa. METHODS: A retrospective study was conducted on SICU patients at Kaohsiung Chang Gung Memorial Hospital from 2010 to 2020, who developed GNB infections following abdominal surgery. RESULTS: Of 442 patients, 237 had S. maltophilia and 205 had non-S. maltophilia GNB infections (including 81 with P. aeruginosa). The overall mortality rate was 44.5%, and S. maltophilia infection emerged as a significant contributor to the mortality rate in patients with GNB infections. S. maltophilia patients had longer mechanical ventilation and SICU stays, with a 30-day mortality rate of 35.4%, higher than the non-S. maltophilia GNB (22.9%) and P. aeruginosa (21%) groups. In-hospital mortality was also higher in the S. maltophilia group (53.2%) compared to the non-S. maltophilia GNB (34.6%) and P. aeruginosa groups (29.6%). Risk factors for acquiring S. maltophilia included a higher Sequential Organ Failure Assessment score and prior broad-spectrum antibiotics use. Older age, polymicrobial infections, and elevated bilirubin were associated with increased 30-day mortality in S. maltophilia patients. CONCLUSION: S. maltophilia infections in post-abdominal surgery patients are linked to higher mortality than non-S. maltophilia GNB and P. aeruginosa infections, emphasizing the need for early diagnosis and treatment to improve outcomes.

VHH CDR-H3 conformation is determined by VH germline usage.

VHHs or nanobodies are single antigen binding domains originating from camelid heavy-chain antibodies. They are used as diagnostic and research tools and in a variety of therapeutic molecules. Analyzing variable domain structures from llama and alpaca we found that VHHs can be classified into two large structural clusters based on their CDR-H3 conformation. Extended CDR-H3 loops protrude into the solvent, whereas kinked CDR-H3 loops fold back onto framework regions. Both major families have distinct properties in terms of their CDR-H3 secondary structure, how their CDR-H3 interacts with the framework region and how they bind to antigens. We show that the CDR-H3 conformation of VHHs correlates with the germline from which the antibodies are derived: IGHV3-3 derived antibodies almost exclusively adopt a kinked CDR-H3 conformation while the CDR-H3 adopts an extended structure in most IGHV3S53 derived antibodies. We do not observe any bias stemming from V(D)J recombination in llama immune repertoires, suggesting that the correlation is the result of selection processes during B-cell development. Our findings demonstrate a previously undescribed impact of germline usage on antigen interaction and contribute to a better understanding on how properties of the antibody framework shape the immune repertoire.

Clinical impact of carbapenems in critically ill patients with valproic acid therapy: A propensity-matched analysis.

Background: Valproic acid (VPA) is one of the most widely used broad-spectrum antiepileptic drugs, and carbapenems (CBPs) remain the drug of choice for severe infection caused by multidrug-resistant bacteria in critically ill patients. The interaction between VPA and CBPs can lead to a rapid depletion of serum VPA level. This may then cause status epilepticus (SE), which is associated with significant mortality. However, the prognostic impact of drug interactions in critically ill patients remains an under-investigated issue. Objective: The aim of this study was to compare the prognosis of critically ill patients treated with VPA and concomitant CBPs or other broad-spectrum antibiotics. Methods: Adult patients admitted to a medical center intensive care unit between January 2007 and December 2017 who concomitantly received VPA and antibiotics were enrolled. The risk of reduced VPA serum concentration, seizures and SE, mortality rate, length of hospital stay (LOS), and healthcare expenditure after concomitant administration were analyzed after propensity score matching. Results: A total of 1,277 patients were included in the study, of whom 264 (20.7%) concomitantly received VPA and CBPs. After matching, the patients who received CBPs were associated with lower VPA serum concentration (15.8 vs. 60.8 mg/L; p < 0.0001), a higher risk of seizures (51.2 vs. 32.4%; adjusted odds ratio [aOR], 2.19; 95% CI, 1.48-3.24; p < 0.0001), higher risk of SE (13.6 vs. 4.7%; aOR, 3.20; 95% CI, 1.51-6.74; p = 0.0014), higher in-hospital mortality rate (33.8 vs. 24.9%; aOR, 1.57; 95% CI, 1.03-2.20; p = 0.036), longer LOS after concomitant therapy (41 vs. 30 days; p < 0.001), and increased healthcare expenditure (US$20,970 vs. US$12,848; p < 0.0001) than those who received other broad-spectrum antibiotics. Conclusion: The administration of CBPs in epileptic patients under VPA therapy was associated with lower VAP serum concentration, a higher risk of seizures and SE, mortality, longer LOS, and significant utilization of healthcare resources. Healthcare professionals should pay attention to the concomitant use of VPA and CBPs when treating patients with epilepsy. Further studies are warranted to investigate the reason for the poor outcomes and whether avoiding the co-administration of VPA and CBP can improve the outcomes of epileptic patients.

Association between Wakeup Frequency at Night and Atherogenic Dyslipidemia: Evidence for Sex Differences.

AIM: This study aimed to determine whether sleep disturbance, defined as the wakeup frequency at night, is associated with atherogenic dyslipidemia and to explore possible sex differences. METHODS: A total of 1,368 adults aged 19-70 years were included in the study of lifestyles and atherogenic dyslipidemia at the National Taiwan University Hospital in the period of 2008-2012. They completed a questionnaire regarding lifestyle information and sleep quality, including sleep hour duration, use of sleeping pills, and wakeup frequency during nighttime sleep. The measured lipid profiles included total cholesterol, triglycerides, low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), non-HDL-C, and small dense LDL-C (sdLDL-C). Multivariate logistic regression was performed to determine habitual interrupted sleep and the odds ratio of atherogenic dyslipidemia following adjustment for conventional risk factors and for sex-based subgroup analysis. RESULTS: A wakeup frequency ≥ 3 times per night was independently associated with an increased risk [odds ratio (95% confidence interval)] of dyslipidemia was 1.96 (1.17-3.28), and non-HDL-C ≥ 160 mg/dL was 1.78 (1.09-2.89). A higher wakeup frequency was associated with increased atherogenic dyslipidemia in women than in men. The multivariate adjusted relative risks for non-HDL ≥ 160 mg/dL and cholesterol ≥ 200 mg/dL were 3.05 (1.27-7.34) and 4.01(1.29-12.45) for female individuals with insomnia and those with a wakeup frequency ≥ 2 times per night, respectively. CONCLUSION: A higher wakeup frequency was associated with atherogenic dyslipidemia in Taiwanese adults, particularly in women. This study also provided another evidence of increasing cardiovascular diseases in subjects with habitual interrupted sleep.