Prediction of post-hepatectomy liver failure by preoperative gadoxetate disodium-enhanced magnetic resonance imaging.

BACKGROUND: Approximately 15% of patients experience post-hepatectomy liver failure after major hepatectomy. Poor hepatocyte uptake of gadoxetate disodium, a magnetic resonance imaging contrast agent, may be a predictor of post-hepatectomy liver failure. METHODS: A retrospective cohort study of patients undergoing major hepatectomy (≥3 segments) with a preoperative gadoxetate disodium-enhanced magnetic resonance imaging was conducted. The liver signal intensity (standardized to the spleen) and the functional liver remnant was calculated to determine if this can predict post-hepatectomy liver failure after major hepatectomy. RESULTS: In 134 patients, low signal intensity of the remnant liver standardized by signal intensity of the spleen in post-contrast images was associated with post-hepatectomy liver failure in multiple logistic regression analysis (Odds Ratio 0.112; 95% CI 0.023-0.551). In a subgroup of 33 patients with lower quartile of functional liver remnant, area under the curve analysis demonstrated a diagnostic accuracy of functional liver remnant to predict post-hepatectomy liver failure of 0.857 with a cut-off value for functional liver remnant of 1.4985 with 80.0% sensitivity and 89.3% specificity. CONCLUSION: Functional liver remnant determined by gadoxetate disodium-enhanced magnetic resonance imaging is a predictor of post-hepatectomy liver failure which may help identify patients for resection, reducing morbidity and mortality.

Salvage Radiotherapy for Relapsed Prostate Cancer after Radical Prostatectomy Is Associated with Normal Life Expectancy.

In patients with prostate cancer (PCa), salvage radiotherapy (SRT) for biochemical progression (BP) after radical prostatectomy (RP) improves PCa-specific survival. However, no prospective randomized trials have compared the effect of SRT with untreated patients. In this analysis of 151 patients who received SRT for post-RP BP, we compared their overall survival (OS) with virtual, age-matched controls (n = 151,000) retrieved from government life tables. We also investigated the risk factors associated with BP and OS and compared the prostate-specific antigen (PSA) doubling times (DTs) before and after SRT for patients with BP. The median follow-up was 9.3 years for BP and 17.4 years for OS. The risk factors significantly affecting BP were Gleason score (p < 0.001), pre-SRT PSA (p = 0.003), and negative surgical margins (p = 0.003). None of these risk factors were associated with OS. In 93 patients with BP after SRT, the median PSADT was significantly prolonged compared with pre-SRT values (3.7 vs. 8.3 months, p < 0.001). The OS did not differ between patients and controls (p = 0.112), and life expectancy was similar, likely due to the survival benefit of SRT. The prolonged PSADT after SRT further supports the beneficial role of SRT in this patient population. However, subsequent treatments were not systematically recorded, which may have affected the results.

Endothelial damage inhibitor preserves the integrity of venous endothelial cells from patients undergoing coronary bypass surgery.

OBJECTIVES: Despite the success of coronary artery bypass graft (CABG) surgery using autologous saphenous vein grafts (SVGs), nearly 50% of patients experience vein graft disease within 10 years of surgery. One contributing factor to early vein graft disease is endothelial damage during short-term storage of SVGs in inappropriate solutions. Our aim was to evaluate the effects of a novel endothelial damage inhibitor (EDI) on SVGs from patients undergoing elective CABG surgery and on venous endothelial cells (VECs) derived from these SVGs. METHODS: SVGs from 11 patients participating in an ongoing clinical registry (NCT02922088) were included in this study, and incubated with both full electrolyte solution (FES) or EDI for 1 h and then examined histologically. In 8 of 11 patients, VECs were isolated from untreated grafts, incubated with both FES and EDI for 2 h under hypothermic stress conditions and then analysed for activation of an inflammatory phenotype, cell damage and cytotoxicity, as well as endothelial integrity and barrier function. RESULTS: The EDI was superior to FES in protecting the endothelium in SVGs (74 ± 8% versus 56 ± 8%, P < 0.001). Besides confirming that the EDI prevents apoptosis in SVG-derived VECs, we also showed that the EDI temporarily reduces adherens junctions in VECs while protecting focal adhesions compared to FES. CONCLUSIONS: The EDI protects the connectivity and function of the SVG endothelium. Our data suggest that the EDI can preserve focal adhesions in VECs during short-term storage after graft harvesting. This might explain the superiority of the EDI in maintaining most of the endothelium in venous CABG surgery conduits.

Prevalence and associations of xerosis cutis, incontinence-associated dermatitis, skin tears, pressure ulcers, and intertrigo in aged nursing home residents: A representative prevalence study.

BACKGROUND: The number of elderly and care-dependent people is increasing, leading to increased risks of adverse skin conditions. Skin care, including prevention and treatment of vulnerable skin, is an essential part of daily nursing practice in long-term residential settings. For many years, the research focus has been on individual skin problems including xerosis cutis, incontinence-associated dermatitis, skin tears, pressure ulcers, and intertrigo, although people may be affected by several at the same time. OBJECTIVES: Aim of the present study was to describe the prevalence and associations of skin conditions relevant to nursing practice in aged nursing home residents. DESIGN: Analysis of baseline data of a cluster-RCT in long-term residential settings. SETTING: The study was conducted in a representative sample of n = 17 nursing homes in the federal state of Berlin, Germany. PARTICIPANTS: Care dependent nursing home residents being 65+ years. METHODS: A random sample of all eligible nursing homes was drawn. Demographic and health characteristics were collected and head-to-toe skin examinations conducted by dermatologists. Prevalence estimates and intracluster correlation coefficients were calculated, and group comparisons conducted. RESULTS: Three hundred fourteen residents with a mean age of 85.4 (SD 7.1) years were included. The majority was affected by xerosis cutis (95.9%, 95% CI 93.6 to 97.8), followed by intertrigo 35.0% (95% CI 30.0 to 40.1), incontinence-associated dermatitis 21.0% (95% CI 15.6 to 26.3), skin tears 10.5% (95% CI 7.3 to 13.8), and pressure ulcers 8.0% (95% CI 5.1 to 10.8). In total, more than half of the nursing home residents were affected by two or more skin conditions at the same time. Several associations between skin conditions and mobility, care dependency, or cognitive impairment were observed. There were no associations between xerosis cutis, incontinence-associated dermatitis, skin tears, pressure ulcers or intertrigo. CONCLUSIONS: The adverse skin and tissue conditions xerosis cutis, incontinence-associated dermatitis, skin tears, pressure ulcers and intertrigo are very common in long-term residential settings, placing a high burden on this population. Although care receivers share similar risk factors and may be affected by several skin conditions at the same time, there are no associations indicating separate aetiological pathways. REGISTRATION: This study is registered at the German Clinical Trials Register (registration number: DRKS00015680; date of registration: January 29th, 2019) and ClinicalTrials.gov (NCT03824886; date of registration: January 31st, 2019).

Narcolepsy-Like Sleepiness: A Symptom of Immediate-Type Reactions in Food-Allergic Children.

BACKGROUND: It has been reported that sometimes children fall asleep and can barely be woken up during allergic reactions on food ingestion. Nevertheless, to date, there is scarce data on narcolepsy-like sleepiness as a symptom of allergic reactions. OBJECTIVE: To investigate the frequency of narcolepsy-like sleepiness during oral food challenges and characterize this symptom regarding comorbidities, eliciting allergens, and severity of reactions. METHODS: Children with immediate-type allergic reactions during oral food challenges (89% were double-blind, placebo-controlled) have been analyzed in this study. Narcolepsy-like sleepiness was defined as a somnolent condition during which patients could barely be woken up again, occurring within 2 hours of food intake and which was not due to drug side effects. Logistic generalized estimating equations were used to explore the effect of age, severity of reactions, and eliciting allergens on the occurrence of narcolepsy-like sleepiness. RESULTS: In 106 (12.5%) of all 848 food-allergic children, narcolepsy-like sleepiness was observed during oral food challenges. Children with eczema had a higher risk of developing narcolepsy-like sleepiness (P = .006). Narcolepsy-like sleepiness occurred most often due to an allergic reaction to hazelnut (P = .009) or other tree nuts (P = .003). Moderate to severe reactions occurred more often than mild reactions (P = .026; odds ratio, 1.521; 95% CI, 1.051-2.202) in children with narcolepsy-like sleepiness. CONCLUSIONS: We were able to show for the first time that narcolepsy-like sleepiness is a frequently occurring clinical manifestation of immediate-type allergic reactions on food ingestion in childhood. Further research is needed to unravel the underlying mechanisms to gain a deeper insight into this underestimated symptom.

Teaching rotary root canal instrumentation using a Peyton teaching approach.

INTRODUCTION: The aim of the study was two evaluate the effectiveness of a Peyton teaching approach for rotary root canal instrumentation, in comparison to the traditional "see one-do one" method. MATERIAL AND METHODS: Forty undergraduate students were randomly divided into two groups (n = 20). Students of the first group (G1) were taught how to use rotary instrumentation using a modified Peyton method, whilst the second group (G2) watched a teaching video (30 min) on the same subject. Both groups instrumented a plastic block and subsequently both mesial canals of an extracted lower molar. The quality of the root canal instrumentation was analysed by 2 blinded observers on video recordings and x-rays. RESULTS: Interobserver correlation was 0.917 (p < .0005; Pearson) for the assessment of the video recordings; students of G1 received significantly more total points (83.55 ± 6.82 points) compared to G2 (69.76 ± 13.82) (p = .001; t-test), the gender had no significant effect on the overall results (p = .444; two-way ANOVA). Significant differences were detected for the categories "initial scouting," "coronal enlargement," "glide path preparation," "preparation using X2 file," "preparation using X3 file" (p < .05; t-test) as well as for the subcategories "sequence of rinse, recapitulation, rinse" (p = .001; t-test) and "recapitulation" (p < .002; t-test). No differences between groups were observed for the radiographic evaluation with respect to working length and canal straightening. CONCLUSION: Teaching rotary instrumentation by using the Peyton approach resulted in improved performance of undergraduate students assessed with a checklist-based process analysis. Enhanced implementation of rotary instrumentation could result in better long-term results of students' root canal treatment.

Bilateral glenohumeral internal rotation deficit (GIRD) in elite gymnasts.

INTRODUCTION: The "Glenohumeral Internal Rotation Deficit (GIRD)" is known as the difference in internal rotation range of motion (IRRM) between the dominant and non-dominant shoulder of overhead athletes as a result of asymmetric loading. As in contrast loading pattern in gymnastics are quite symmetric and structural changes often occur bilaterally, the question arises if GIRD might develop bilaterally in gymnasts as one source of common bilateral shoulder pathologies and to search for underlying structural adaptations. MATERIALS AND METHODS: A group of 35 elite gymnasts (8-24 years) were recruited from a local Olympic Training Centre and compared to a paired cohort of 28 non-overhead athletes. Clinical examinations, digital range of motion (ROM)-measurement, ultrasonographic humeral torsion measurement, and standardized MRI scans of both shoulders were obtained and examined for structural pathologies, cross-sectional areas (CSA) of the rotator cuff muscles and capsular thickness. RESULTS: ROM-measurements showed significant decrease in IRRM in the gymnasts groups by age, with IRRM of 48.6° (SD: 8.4°, CI 95%: 43.0-54.3°) at age group 1 (8-10 years) and IRRM of 10° (SD: 11.4°; CI 95%: 0-22.0°) at age group 4 (18-26 years), that was statistically significant for the entire cohort (p = 0.017) compared to the controls. CSA were not significantly different between the cohorts, while there was a slightly increased humeral retrotorsion in the gymnasts as well as a statistically significant posterior capsular thickening. CONCLUSION: A new bilateral form of GIRD was identified in higher age groups of youth and senior elite gymnasts enrolled in this study. Despite to former definition of GIRD there was no compensatory increase in external rotation range of motion (ERRM) but an association with posterior capsular thickening, while there was no periscapular muscle hypertrophy. Humeral retrotorsion was also slightly increased in the gymnasts group.

Incremental value of mineralocorticoid receptor antagonists in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

AIMS: We investigated the incremental advantage in terms of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction in patients affected by heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (S/V) and mineralocorticoid receptor antagonists (MRA) versus patients treated with S/V only. METHODS: Consecutive adult patients with a left ventricular ejection fraction (LVEF) of ≤40% who were followed in our outpatient clinic from January 2016 to December 2019 and treated with S/V were analysed. RESULTS: Out of eligible 147 patients, 99 were treated with S/V+MRA at baseline and 48 patients were treated with S/V. Patients treated with S/V+MRA were significantly younger (61.5 vs 67.8 years, p=0.006), had better basal renal function (serum creatinine 1.2 vs 1.4 mg/dL, p=0.006) and lower LVEF (30.9% vs 33.1%, p=0.039). At follow-up at 8-16 months, 84 out of 99 patients continued to be on S/V+MRA, and 39 out of 48 patients continued to be on S/V. Between these two groups, at follow-up, LVEF did not vary significantly, ΔNT-proBNP was not significantly different (-215.7 vs -165.9 pg/mL, p=0.93) and neither was the rate of hospitalisation for heart failure (9.5% vs 12.8%, p=0.58). Using general linear models, both age and basal NT-proBNP influenced significantly ΔNT-proBNP (respectively, p=0.002; p=0.005), while treatment with S/V+MRA versus S/V only did not significantly influence ΔNT-proBNP (p=0.462). CONCLUSION: Even with the limitations of a small retrospective study, our results generate the hypothesis that MRA might not provide any additional value in patients with HFrEF treated with S/V. Larger studies are needed to test if MRA should remain a standard treatment in patients with HFrEF treated with S/V.

When Treatment of Pulmonary Emphysema with Endobronchial Valves Did Not Work: Evaluation of Quantitative CT Analysis and Pulmonary Function Tests Before and After Valve Explantation.

Purpose: To investigate changes in quantitative CT analysis (QCT) and pulmonary function tests (PFT) in pulmonary emphysema patients who required premature removal of endobronchial valves (EBV). Patients and Methods: Our hospital's medical records listed 274 patients with high-grade COPD (GOLD stages 3 and 4) and pulmonary emphysema who were treated with EBV to reduce lung volume. Prior to intervention, a complete evaluation was performed that included quantitative computed tomography analysis (QCT) of scans acquired at full inspiration and full expiration, pulmonary function tests (PFT), and paraclinical findings (6-minute walking distance test (6MWDT) and quality of life questionnaires). In 41 of these 274 patients, EBV treatment was unsuccessful and the valves had to be removed for various reasons. A total of 10 of these 41 patients ventured a second attempt at EBV therapy and underwent complete reevaluation. In our retrospective study, results from three time points were compared: Before EBV implantation (BL), after EBV implantation (TP2), and after EBV explantation (TP3). QCT parameters included lung volume, total emphysema score (TES, ie, the emphysema index) and the 15th percentile of lung attenuation (P15) for the whole lung and each lobe separately. Differences in these parameters between inspiration and expiration were calculated (Vol. Diff (%), TES Diff (%), P15 Diff (%)). The results of PFT and further clinical tests were taken from the patient's records. Results: We found persistent therapy effect in the target lobe even after valve explantation together with a compensatory hyperinflation of the rest of the lung. As a result of these two divergent effects, the volume of the total lung remained rather constant. Furthermore, there was a slight deterioration of the emphysema score for the whole lung, whereas the TES of the target lobe persistently improved. Conclusion: Interestingly, we found evidence that, contrary to our expectations, unsuccessful EBV therapy can have a persistent positive effect on target lobe QCT scores.

Comparison of two skin protection regimes for the Prevention of Incontinence-associated Dermatitis in geriatric care (PID): a study protocol for an exploratory randomised controlled pragmatic trial.

INTRODUCTION: The majority of aged long-term care receivers and patients in geriatric acute care are affected by some form of incontinence. These individuals are at risk of developing incontinence-associated dermatitis (IAD), a common type of irritant contact dermatitis caused by repeated and prolonged direct contact of the skin with urine and stool. The prevalence of IAD in these settings is high. Preventive measures include mild skin cleansing and the application of skin protecting leave-on products. Available evidence is weak regarding the comparative performance of different skin protection strategies and products due to a lack of confirmatory trials using relevant comparators and endpoints. Therefore, the overall aim of this exploratory trial is to compare the effects of three skin protection strategies to estimate effect sizes of the recently published core outcomes in IAD research. METHODS AND ANALYSIS: A pragmatic three-arm, assessor-blinded, randomised controlled, exploratory trial with parallel group design will be performed, comparing film-forming and lipophilic skin protecting leave-on products for IAD prevention with standard incontinence care alone. The trial will be conducted in geriatric nursing homes and geriatric acute care settings in the federal state of Berlin, Germany. A total of n=210 participants being incontinent of urine and stool will be included. Outcomes include IAD incidence, erythema, erosion, maceration, IAD-related pain, patient satisfaction, safety, feasibility and compliance. IAD incidence of the control and intervention groups will be compared to estimate effect sizes, and the procedural feasibility of the intervention will be tested to plan a possible subsequent confirmatory randomised controlled trial. ETHICS AND DISSEMINATION: The study received the approval of the ethics committee of Charité-Universitätsmedizin Berlin (EA4/043/22). Results will be disseminated through peer-reviewed open-access journals and international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05403762) and German Clinical Trials Register (Deutsches Register Klinischer Studien, or DRKS) (DRKS00028954).

Contrast-enhanced ultrasound (CEUS) in characterization of inconclusive cervical lymph nodes: a meta-analysis and systematic review.

Lymph node metastases are common in malignant neoplasms of head and neck. Since cervical lymph nodes (cLN) are localized superficially, ultrasound (US) represents the primary imaging modality. The aim of the study is to report the value of US and contrast-enhanced ultrasound (CEUS) and their diagnostic confidence in the characterization of inconclusive cLN. A systematic review was performed using the literature data base PubMed. Results were filtered (published in a peer-reviewed journal, full-text available, published within the last ten years, species human, English or German full-text) and inclusion criteria were clearly defined (cohort with lymphadenopathy or malignancy in head and neck ≥ 50 patients, histological confirmation of malignant imaging findings, performance of CEUS as outcome variable). The results were quantified in a meta-analysis using a random-effects model. Overall, five studies were included in qualitative and quantitative analysis. The combination of non-enhanced US and CEUS enlarges the diagnostic confidence in the characterization of lymph nodes of unclear dignity. The pooled values for sensitivity and specificity in the characterization of a malignant cervical lymph node using US are 76% (95%-CI 66-83%, I2 = 63%, p < 0.01) and 80% (95%-CI 45-95%, I2 = 92%, p < 0.01), compared to 92% (95%-CI 89-95%, I2 = 0%, p = 0.65) and 91% (95%-CI 87-94%, I2 = 0%, p = 0.40) for the combination of US and CEUS, respectively. Consistent results of the included studies show improved diagnostic performance by additional CEUS. Nevertheless, more prospective studies are needed to implement CEUS in the diagnostic pathway of cLN.

The Prognostic Significance of p16 and its Role as a Surrogate Marker for Human Papilloma Virus in Oral Squamous Cell Carcinoma: An Analysis of 281 Cases.

BACKGROUND/AIM: This study analyzed the expression of p16 in a large cohort of patients suffering from oral squamous cell carcinoma (OSCC) who received initial surgical therapy in order to evaluate the prognostic significance of p16 expression and to analyze its value as a surrogate marker to determine human papilloma virus (HPV) status. MATERIALS AND METHODS: Immunohistochemical staining of p16 was performed on tissue microarrays. Different expression levels of p16 (>25%; >50%; ≥70%) with a moderate to strong intensity were correlated with the clinical outcome. HPV DNA was analyzed by polymerase chain reaction (PCR). RESULTS: A total of 281 patients were included in this study. The p16 expression obtained using the abovementioned three different cutoffs did not significantly influence 5-year overall survival (OS) (p=0.23; p=0.45; p=0.23) nor recurrence-free survival (RFS) (p=0.79; p=0.45; p=0.142). In univariate Cox regression analysis, the p16 expression level was not a risk factor for OS (HR=0.637; 95%CI=0.271-1.5; p=0.300) and RFS (HR=0.74; 95%CI=0.339-1.61; p=0.449). A total of 17 patients (6.0%) were p16 positive with a cutoff ≥70%. HPV DNA was found in 4/11 of these cases by PCR, resulting in a positive predictive value of 0.36. In patients receiving adjuvant radio(chemo)therapy, a significantly (p=0.042) longer OS was observed in patients with p16 expression greater than 25% vs. ≤25%. CONCLUSION: In comparison with OPSCC, (strong) p16 positivity is rare in OSCC; however, in patients receiving primary surgery with adjuvant radio(chemo)therapy, p16 expression is associated with a higher survival rate. In conjunction with prior studies, p16 does not seem to be a reliable surrogate marker for HPV infection in OSCC.

Liver Venous Deprivation (LVD) Versus Portal Vein Embolization (PVE) Alone Prior to Extended Hepatectomy: A Matched Pair Analysis.

BACKGROUND: To investigate whether liver venous deprivation (LVD) as simultaneous, portal vein (PVE) and right hepatic vein embolization offers advantages in terms of hypertrophy induction before extended hepatectomy in non-cirrhotic liver. MATERIALS AND METHODS: Between June 2018 and August 2019, 20 patients were recruited for a prospective, non-randomized study to investigate the efficacy of LVD. After screening of 134 patients treated using PVE alone from January 2015 to August 2019, 14 directly matched pairs regarding tumor entity (cholangiocarcinoma, CC and colorectal carcinoma, CRC) and hypertrophy time (defined as time from embolization to follow-up imaging) were identified. In both treatment groups, the same experienced reader (> 5 years experience) performed imaging-based measurement of the volumes of liver segments of the future liver remnant (FLR) prior to embolization and after the standard clinical hypertrophy interval (~ 30 days), before surgery. Percentage growth of segments was calculated and compared. RESULTS: After matched follow-up periods (mean of 30.5 days), there were no statistically significant differences in relative hypertrophy of FLRs. Mean ± standard deviation relative hypertrophy rates for LVD/PVE were 59 ± 29.6%/54.1 ± 27.6% (p = 0.637) for segments II + III and 48.2 ± 22.2%/44.9 ± 28.9% (p = 0.719) for segments II-IV, respectively. CONCLUSIONS: LVD had no significant advantages over the standard method (PVE alone) in terms of hypertrophy induction of the FLR before extended hepatectomy in this study population.

Is There an Association between Intra-Operative Detection of Pathogens in Subcutaneous Tissue and Surgical Site Infections? Results from a Prospective Study.

Background: Surgical site infections (SSIs) are a common complication in visceral surgery. Pathogens causing SSIs vary depending on the type of surgery. Patients and Methods: Within the scope of the Reduction of Postoperative Wound Infections by Antiseptica (RECIPE) trial we analyzed the pathogens cultured in intra-operative, subcutaneous swabs and in swabs from SSI in a single-center, prospective, randomized controlled study. Definition of SSI complied with the criteria of the U.S. Centers for Disease Control and Prevention (CDC). Results: The overall rate of SSI was 28.2% in 393 patients. Colorectal surgery was performed in 68.2% of elective laparotomies. Pathogens were more often detected in intra-operative subcutaneous swabs in patients who developed SSIs than in patients who did not develop SSIs (64.4% vs. 38.0%; p < 0.001). Enterococci were found in 29.1% of intra-operative swabs in patients with SSIs, followed by Escherichia coli in 15.5%. A higher rate of Enterococcus faecium was found in patients with anemia versus those without anemia (9.2% vs. 2.3%; p = 0.006) and in patients who smoked versus those who did not (11.8% vs. 3.6%; p = 0.008). A positive subcutaneous swab (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.47-4.29; p = 0.001), pre-operative anemia (OR, 1.84; 95% CI, 1.08-3.13; p = 0.016), and renal insufficiency (OR, 2.15; 95% CI, 1.01-4.59; p = 0.048) were risk factors for SSIs. Conclusions: There is an association between the intra-operative detection of pathogens in subcutaneous tissue and the development of SSIs in visceral surgery. The most prevalent pathogens causing SSIs were enterococci and Escherichia coli. More efforts are justified to reduce subcutaneous colonization with pathogens, for example by using intra-operative wound irrigation with polyhexanide solution. This trial is registered at www.ClinicalTrials.gov (ID: NCT04055233).

Adverse events after antipsychotic discontinuation: an individual participant data meta-analysis.

BACKGROUND: Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. METHODS: For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's database for randomised controlled trials of antipsychotics from database inception until May 6, 2021. We included placebo-controlled antipsychotic randomised controlled trials with individual participant data of participants (aged ≥ 18 years, of any sex and ethnicity) with schizophrenia, schizoaffective disorder, or bipolar disorder. Studies were excluded if treatment with antidepressants, lithium, or antiepileptic drugs was initiated as additive therapy at the start of the placebo phase. Starting from the screening or washout phase, we divided participants who were randomised to placebo into two groups: the discontinuation group (participants who discontinued prestudy antipsychotics at the start of the screening or washout phase) and control group (participants who did not take prestudy antipsychotics for at least 4 weeks before the start of the screening or washout phase). Participants were excluded from the discontinuation and control groups if they discontinued prestudy treatment with antidepressants, lithium, or antiepileptic drugs up to 4 weeks before baseline, received an antipsychotic as a tolerability test, or received a long-acting injection of an antipsychotic within 12 weeks before baseline. In the discontinuation group, individuals were excluded if they discontinued prestudy antipsychotic treatment more than 3 days before, or any day after, the start of screening or washout phase. The prespecified primary outcome was occurrence of at least one new somatic adverse event with an onset within 4 weeks after the start of the screening or washout phase. We implemented a generalised linear model that accounted for potential confounders, to estimate the effect of antipsychotic discontinuation. This study is registered with PROSPERO (CRD42021224350). FINDINGS: We identified 409 records of which 18 were eligible and included in the analysis. From these 18 studies, 692 individuals (242 [35·0%] women and 450 [65·0%] men) were eligible for the discontinuation group and 935 individuals (339 [36·3%] women and 596 [63·7%] men) were eligible for the control group (median age in both groups: 39 years [IQR 30-47]). New somatic adverse events occurred in 295 (43%) individuals in the discontinuation group and 293 (31%) individuals in the control group (OR 1·74; 95% CI 1·27-2·39; τ2=0·15; moderate strength of evidence). New psychiatric adverse events were also more frequent in the discontinuation group than the control group (OR 2·01; 95% CI 1·38-2·94). Longer duration of treatment before discontinuation (OR for doubling the duration of treatment: 1·08; 95% CI 1·01-1·14) was associated with a higher probability of new somatic adverse events after antipsychotic discontinuation, and tapered discontinuation (compared with abrupt discontinuation: 0·54; 0·32-0·91) and no history of somatic illness (compared with history of somatic illness: 0·63; 0·43-0·91) were associated with lower probabilities of new somatic adverse events after antipsychotic discontinuation. The risk of bias was moderate in 13 (72·2%) studies and serious in five (27·8%) studies. INTERPRETATION: We detected moderate evidence of emerging somatic adverse events after discontinuation of first-generation and second-generation antipsychotics, particularly after discontinuation of longer durations of treatment. Tapered discontinuation can mitigate the risk of emerging somatic adverse events after antipsychotic discontinuation. These findings have implications for the safety of treatment discontinuation and could be used for tailored treatment planning. FUNDING: German Research Foundation.

Factors influencing the presence of Candida dubliniensis and other non-albicans species in patients with oral lichen planus: a retrospective observational study.

OBJECTIVES: The epidemiologic distribution of non-albicans species in the oral cavity of oral lichen planus (OLP) patients remains uncertain. Therefore, the aim of this study was to identify factors associated with the presence of C. dubliniensis and other non-albicans species. Furthermore, independent risk factors for Candida superinfection in OLP should be identified. MATERIAL AND METHODS: Epidemiologic data and microbiological findings from 268 symptomatic OLP patients who underwent continuous oral swab culture over a 5-year period (2015-2019) were retrospectively reviewed. Candida species identification and semi-quantification were obtained by culture on CHROMagar Candida, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: C. albicans was the most frequently isolated species (72.3%), followed by C. glabrata (7.3%), C. dubliniensis (5.8%), C. krusei and C. parapsilosis (both 2.6%). The presence of C. dubliniensis was significantly associated with tobacco smoking. Other non-albicans spp. were significantly more often detected in patients using removable dentures. Increasing age and the intake of psychotropic drugs were identified as independent risk factors of Candida superinfection in OLP. CONCLUSION: In OLP patients, certain local and systemic factors increase the risk of carrying potentially drug-resistant Candida species and the development of Candida superinfection of OLP lesions. CLINICAL RELEVANCE: Due to the frequent detection of non-albicans species in OLP, resistance or at least reduced sensitivity to azole antifungals should be expected, especially in smokers and patients using removable dentures. In the case of oral complaints, a superinfection with Candida should be considered, whereby older patients and patients taking psychotropic drugs have an increased risk for oral infection with Candida.

Impact of Ventilation Modes on Bronchoscopic Chartis Assessment Outcome in Candidates for Endobronchial Valve Treatment.

BACKGROUND: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. METHODS: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. RESULTS: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes. CONCLUSION: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV.

The impact of surgical site infection-a cost analysis.

PURPOSE: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. METHODS: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. RESULTS: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 €; 19.703 USD (IQR 21.638 €; 25.552 USD) vs. median 11.235 €; 13.276 USD (IQR 11.564 €; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 €; 7.870 USD with SSI vs. median 5.040 €; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 €; 9.924 USD with SSI vs. median 4.690 €; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 €; 14.237 USD vs. median 12.793 €; 15.107 USD in the polyhexanide group (p = 0.52). CONCLUSION: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide.

Prognostic Significance of Estrogen Receptor Alpha in Oral Squamous Cell Carcinoma.

INTRODUCTION: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. MATERIAL AND METHODS: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan-Meier method and log-rank test. RESULTS: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27-96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα-) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616-11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073-37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. CONCLUSION: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

Validation and Classification of the 9-Item Voice Handicap Index (VHI-9i).

The international nine-item Voice Handicap Index (VHI-9i) is a clinically established short-scale version of the original VHI, quantifying the patients' self-assessed vocal handicap. However, the current vocal impairment classification is based on percentiles. The main goals of this study were to establish test-retest reliability and a sound statistical basis for VHI-9i severity levels. Between 2009 and 2021, 17,660 consecutive cases were documented. A total of 416 test-retest pairs and 3661 unique cases with complete multidimensional voice diagnostics were statistically analyzed. Classification candidates were the overall self-assessed vocal impairment (VHIs) on a four-point Likert scale, the dysphonia severity index (DSI), the vocal extent measure (VEM), and the auditory-perceptual evaluation (GRB scale). The test-retest correlation of VHI-9i total scores was very high (r = 0.919, p < 0.01). Reliability was excellent regardless of gender or professional voice use, with negligible dependency on age. The VHIs correlated best with the VHI-9i, whereas statistical calculations proved that DSI, VEM, and GRB are unsuitable classification criteria. Based on ROC analysis, we suggest modifying the former VHI-9i severity categories as follows: 0 (healthy): 0 ≤ 7; 1 (mild): 8 ≤ 16; 2 (moderate): 17 ≤ 26; and 3 (severe): 27 ≤ 36.