Natural IgG protects against early dissemination of vesicular stomatitis virus.

Neonatal Fc receptor (FcRn) recycles immunoglobulin G, and inhibition of FcRn is used clinically for treatment of autoimmune diseases. In this work, using the vesicular stomatitis virus (VSV) mouse infection model system, we determined the role of FcRn during virus infection. While induction of neutralizing antibodies and long-term protection of these antibodies was hardly affected in FcRn deficient mice, FcRn deficiency limited the amount of natural IgG (VSV-specific) antibodies. Lack of natural antibodies (nAbs) limited early control of VSV in macrophages, accelerated propagation of virus in several organs, led to the spread of VSV to the neural tissue resulting in fatal outcomes. Adoptive transfer of natural IgG into FcRn deficient mice limited early propagation of VSV in FcRn deficient mice and enhanced survival of FcRn knockout mice. In line with this, vaccination of FcRn mice with very low dose of VSV prior to infection similarly prevented death after infection. In conclusion we determined the importance of nAbs during VSV infection. Lack of FcRn limited nAbs and thereby enhanced the susceptibility to virus infection.

Cerebral and Aortic Aneurysms in Electroconvulsive Therapy Patients: A Systematic Review and Results From 12 Years of Screening.

INTRODUCTION: Theoretically, the procedural risk of electroconvulsive therapy (ECT) could be increased in the presence of undetected aneurysms due to the hemodynamic changes associated with ECT. However, empirical evidence is limited to few individual case reports and case series. METHODS: We performed a systematic review of available evidence on ECT treatment in patients with intracranial aneurysms and untreated aortic aneurysms and we retrospectively analyzed data from 252 consecutive patients referred for ECT at the Department of Psychiatry, Psychotherapy and Psychosomatics of Siegen Hospital, Germany, who received magnetic resonance angiographies and abdominal sonographies as part of their routine pre-ECT workup. RESULTS: Of 252 patients referred for ECT, 5 (2.0%) were found to have an intracerebral aneurysm and 1 (0.4%) was found to have an abdominal aortic aneurysm. These cases are reported in detail together with 2 additional cases of aortic aneurysms from the Central Institute of Mental Health, Mannheim, Germany. Electroconvulsive therapy was performed without complications in all 8 cases. CONCLUSIONS: Aneurysms might occur in ECT patients at a similar rate as in the general population. The number of ECTs performed annually in mostly unscreened patients suggests that there might be a significant number of patients with undetected aneurysms in whom ECT is performed without reported complications.

No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters.

INTRODUCTION: Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality. METHODS: We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing. RESULTS: Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration. CONCLUSIONS: Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.

Evolution of Length-Dependent Properties of Discrete n-Type Oligomers Prepared via Scalable Direct Arylation.

Efficient organic electronic devices are fabricated from both small molecules and disperse polymers, but materials with characteristics in between remain largely unexplored. Here, we present a gram-scale synthesis for a series of discrete n-type oligomers comprising alternating naphthalene diimide (NDI) and bithiophene (T2). Using C-H activation, discrete oligomers of type T2-(NDI-T2)n (n ≤ 7) and persistence lengths up to ∼10 nm are made. The absence of protection/deprotection reactions and the mechanistic nature of Pd-catalyzed C-H activation allow one to produce symmetrically terminated species almost exclusively, which is key to the fast preparation, high yields, and the general success of the reaction pathway. The reaction scope includes different thiophene-based monomers, end-capping to yield NDI-(T2-NDI)n (n ≤ 8), and branching at T2 units by nonselective C-H activation under certain conditions. We show how the optical, electronic, thermal, and structural properties depend on oligomer length along with a comparison to the disperse, polymeric analogue PNDIT2. From theory and experiments, we find that the molecular energy levels are not affected by chain length resulting from the strong donor-acceptor system. Absorption maxima saturate for n = 4 in vacuum and for n = 8 in solution. Linear oligomers T2-(NDI-T2)n are highly crystalline with large melting enthalpies up to 33 J/g; NDI-terminated oligomers show reduced crystallinity, stronger supercooling, and more phase transitions. Branched oligomers and those with bulky thiophene comonomers are amorphous. Large oligomers exhibit similar packing characteristics compared to PNDIT2, making these oligomers ideal models to study length-structure-function relationships at constant energy levels.

Imaging via Correlation of X-Ray Fluorescence Photons.

We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecond-duration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.

Physician-led medication reviews in polypharmacy patients treated with at least 12 medications in a type 2 diabetes outpatient clinic: A randomised trial.

AIMS: Medication reviews can be used to promote appropriate pharmacotherapy and negate the harmful consequences of polypharmacy. This study aimed to evaluate the effect of physician-led medication reviews and increased cross-sectoral communication as a supplement to standard care in a type 2 diabetes outpatient clinic. METHODS: This pragmatic randomised clinical trial enrolled patients with type 2 diabetes treated with at least 12 medications. The subjects were randomised to either standard care (standard care consultation at the outpatient clinic) or standard care plus a medication review consultation and increased cross-sectoral communication. The primary outcome was the number of medications used after six months. Health-related quality of life was quantified using the EuroQoL 5-dimension 5-level (EQ5D-5 L) questionnaire. RESULTS: We recruited 50 participants with a median age of 72 (IQR 67-75) years. The mean number of medications per patient changed from 17.9 to 14.3 in the intervention group and 17.6 to 17.2 in the control group (rate ratio 0.81). The reasons for discontinuations were medication no longer indicated (60%), safety issues (20%), efficacy issues (15%) or patient preferences (5%). There was a significant difference in the change in health-related quality of life (EQ5D-5 L index score) in favour of the intervention (0.111, 95% CI 0.001 to 0.221). CONCLUSIONS: Physician-led medication reviews and increased cross-sectoral communication in patients with type 2 diabetes treated with at least 12 medications reduced the number of medications used and improved health-related quality of life. Implementing and further investigating similar interventions as standard care seems reasonable.

Medication changes implemented during medication reviews and factors related to deprescribing: Posthoc analyses of a randomized clinical trial in geriatric outpatients with polypharmacy.

AIMS: To provide posthoc analyses of a clinical trial that reported beneficial effects of medication reviews on health-related quality of life. Specifically, to describe the medication changes with a focus on deprescribing and to explore patient- and medication-related factors that may identify patients most likely to benefit from medication reviews. METHODS: Posthoc analyses of data from a pragmatic, nonblinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients treated with ≥9 medicines. RESULTS: In the medication review group (n = 196), 26% of the medicines prescribed at baseline were discontinued with 82% still being discontinued after 13 months. The most common reason for discontinuation was lack of indication (72% of discontinuations). The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/15 = 73% discontinued vs. 1/12 = 8% in usual care), acetylsalicylic acid (20/48 = 42% vs. 2/47 = 4%), simvastatin (18/48 = 38% vs. 2/58 = 3%), zopiclone (23/59 = 39% vs. 4/54 = 7%), quinine (9/14 = 64% vs. 6/16 = 38%), citalopram (4/18 = 22% vs. 0/20 = 0%) and tramadol (18/37 = 49% vs. 8/30 = 27%). Factors associated with number of deprescribed medicines included: number of prescribed medicines, Drug Burden Index, patient motivation for medicine changes, and prescriptions of metoclopramide, iron preparations, antidepressants other than selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or drugs for urinary incontinence. CONCLUSION: Physician-led medication reviews resulted in persistent deprescribing of medicines in older polypharmacy patients treated with ≥9 medicines. Motivation for having their medicine changed, treatment with more medicines, and a higher burden of sedative and anticholinergic medicines characterized the patients most likely to benefit from physician-led medication reviews.

Age-Dependent Dose Increase During an Acute Electroconvulsive Therapy Series.

INTRODUCTION: Electroconvulsive therapy (ECT) dose is highly relevant for ECT efficacy as well as adverse effects. It is often based on seizure threshold (ST). Studies have shown that ST increases over the course of an ECT series. Clinical observation suggests that this rise might be more pronounced in geriatric patients. METHODS: Retrospectively, we analyzed ECT dose during the first 20 ECT treatments in 472 patients undergoing ECT. Dose adjustments were assessed in relation to patients' age using generalized least squares regression analysis. Response was defined as Clinical Global Impression Improvement Scale < 4. RESULTS: Dose increased in all patients during the course of the ECT series (mean initial dose, 64.97 ± 68.04 mC; at 10th ECT, 385.46 ± 211.28 mC). Dose was significantly correlated with ECT treatment number, electrode placement, and the interaction between age and ECT treatment number. In other words, dose increase was significantly positively correlated with increasing age, that is dose increased more in older compared with younger patients during the course of an ECT series ( z = 9.47, P < 0.001). Response was not correlated with age-dependent dose increase; however, the length of the ECT series in responders was negatively associated with the dose increase from the first to the seventh ECT session ( F = 5.28, P = 0.0228). CONCLUSIONS: Our results indicate that ST increases more rapidly during the course of an ECT series in older compared with younger patients. To ensure high efficacy throughout the course of treatment, attention should be paid to decreasing seizure quality, especially in older patients, and dose should be adjusted accordingly.

[Climate change, biodiversity loss and pollution: consequences for psychiatry]. / Klimawandel, Biodiversitätsverlust und Verschmutzung: Folgen für die Psychiatrie.

The climate crisis, loss of biodiversity and increasing global pollution are a threat to mental health. Comprehensive transformations are needed to overcome these crises, which will also affect the mental healthcare system. If done correctly these change processes can seize the chance to improve mental health while at the same time addressing the crises. This includes avoiding the need for psychiatric treatment by strengthening the focus on mental health promotion and prevention, and also considering environmental aspects when targetting therapy procedures. In addition, by focusing on nutrition, mobility and the effects of nature, patients can be empowered to increase their mental resilience whilst reducing the negative effects on the environment. At the same time, the mental healthcare system must adapt to changing environmental conditions: increasing heat waves make protective measures necessary, especially for people with mental illnesses and increasing extreme weather events can lead to shifts in the spectrum of illnesses. Appropriate funding mechanisms will have to be established to support mental healthcare throughout this transformation.

[Acute catatonia]. / Akute katatone Zustände.

BACKGROUND: Catatonia is an underdiagnosed psychomotor syndrome that can occur in the context of various mental and somatic diseases. Malignant catatonia is particularly relevant in the context of intensive medical care. Clear recommendations in guidelines are missing. OBJECTIVE: To present the current state of the diagnosis and treatment of catatonia, especially malignant catatonia. MATERIAL AND METHODS: The literature was evaluated with respect to acute catatonic conditions, with a special focus on the differential diagnosis, relevance to intensive medical care and treatment of catatonia. RESULTS: In psychiatric inpatients, catatonic syndromes are relatively frequent with a prevalence between 9% and 17%, and in neurological patients somewhat less frequent with a prevalence of 3.3%. There is a clear recommendation for pharmacological treatment with lorazepam. Additional electroconvulsive therapy (ECT) should be considered as early as possible, especially in cases not responding to benzodiazepines. Response rates to ECT have been shown to be 80-100%. In malignant catatonia, ECT should be performed immediately as an emergency indication. CONCLUSION: Several factors lead to the underdiagnosis of catatonia. It is problematic that even life-threatening malignant catatonia is often not recognized as such, although there is a mortality of about 50% if untreated. The best treatment outcome is achieved with a combination of benzodiazepines and ECT. The treatment of severe malignant catatonia represents an emergency indication for ECT.

SIRT1-mediated deacetylation of FOXO3a transcription factor supports pro-angiogenic activity of interferon-deficient tumor-associated neutrophils.

Angiogenesis plays an important role during tumor growth and metastasis. We could previously show that Type I interferon (IFN)-deficient tumor-associated neutrophils (TANs) show strong pro-angiogenic activity, and stimulate tumor angiogenesis and growth. However, the exact mechanism responsible for their pro-angiogenic shift is not clear. Here, we set out to delineate the molecular mechanism and factors regulating pro-angiogenic properties of neutrophils in the context of Type I IFN availability. We demonstrate that neutrophils from IFN-deficient (Ifnar1-/- ) mice efficiently release pro-angiogenic factors, such as VEGF, MMP9 or BV8, and thus significantly support the vascular normalization of tumors by increasing the maturation of perivascular cells. Mechanistically, we could show here that the expression of pro-angiogenic factors in neutrophils is controlled by the transcription factor forkhead box protein O3a (FOXO3a), which activity depends on its post-translational modifications, such as deacetylation or phosphorylation. In TANs isolated from Ifnar1-/- mice, we observe significantly elevated SIRT1, resulting in SIRT1-mediated deacetylation of FOXO3a, its nuclear retention and activation. Activated FOXO3a supports in turn the transcription of pro-angiogenic genes in TANs. In the absence of SIRT1, or after its inhibition in neutrophils, elevated kinase MEK/ERK and PI3K/AKT activity is observed, leading to FOXO3a phosphorylation, cytoplasmic transfer and inactivation. In summary, we have found that FOXO3a is a key transcription factor controlling the angiogenic switch of neutrophils. Post-translational FOXO3a modifications regulate its transcriptional activity and, as a result, the expression of pro-angiogenic factors supporting development of vascular network in growing tumors. Therefore, targeting FOXO3a activity could provide a novel strategy of antiangiogenic targeted therapy for cancer.

Provision of Electroconvulsive Therapy During the COVID-19 Pandemic: A Survey Among Clinics in Germany, Austria, and Switzerland.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic has had a marked impact on psychiatry. Capacity reductions also affected electroconvulsive therapy (ECT), even though ECT is an essential rather than an elective procedure. We sent a survey to all 197 clinics in Germany, Austria, and Switzerland with an ECT service between March and May 2021 to provide an overview of the changes made to ECT services in these countries during the acute phase of the COVID-19 pandemic. More than a quarter of the clinics (27.0%) reported a temporary suspension of all ECT treatments, and 28.2% of the clinics reported reductions of up to 75%. Maintenance ECT was suspended in 46.7% of the clinics and reduced by up to 75% in 30.6% of the clinics. At the time of the survey, 40.8% of the clinics still reported lower numbers of ECT treatments compared with the prepandemic situation. Reasons for the reduced number of ECT treatments included patient safety and testing measures, personnel shortages in the anesthesiology departments, and limited availability of rooms. The COVID-19 pandemic had and continues to have a marked negative impact on the provision of ECT in clinics in Germany, Austria, and Switzerland. To avoid negative consequences for patients, ECT clinics should urgently take steps to provide ECT services without disruptions.

Electroconvulsive Therapy in Children and Adolescents in Germany-A Case Series From 3 University Hospitals.

OBJECTIVE: Electroconvulsive therapy (ECT) is a well-established, safe, and efficacious treatment for severe psychiatric disorders. In children and adolescents, it is used much less frequently than in adults, likely because of a lack of knowledge. METHODS: We retrospectively analyzed all patients aged 12 to 17 years who completed a course of ECT at 3 psychiatric university hospitals in Germany between 2010 and 2020. Clinical Global Impression Severity (CGI-S) scores were assessed based on electronic medical records. Changes in CGI-S scores were assessed using a paired samples t test. Predictors for response and remission were assessed using binomial logistic regression. RESULTS: We included 32 patients. The CGI-S scores improved significantly from before to after ECT treatment (6.9 vs 3.9, t = 10.0, P < 0.01). A total of 40.6% of patients responded (CGI ≤ 3) and 21.9% remitted (CGI ≤ 2). The number of ineffective medication trials in the 6 months before ECT treatment was significantly associated with response (odds ratio, 0.54; P = 0.028) and remission (odds ratio, 0.31; P = 0.048). Five patients reported subjective cognitive adverse effects, 2 patients exhibited a prolonged seizure, 1 patient reported headaches, and 1 patient experienced a mild allergic reaction after anesthesia with etomidate. A total of 65.6% of patients experienced no adverse effects at all. CONCLUSIONS: This retrospective analysis found ECT to be effective and safe in children and adolescents irrespective of their main diagnosis. The reported data point to the importance of an early use of ECT for severe psychiatric diseases in child and adolescent psychiatry.

Empirical ratio of the combined use of S-ketamine and propofol in electroconvulsive therapy and its impact on seizure quality.

Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders. In certain cases, ECT-associated anaesthesia can be improved by the use of ketofol (i.e., S-ketamine + propofol). We aimed to evaluate the empirical mixing ratio of ketofol in these cases for better clinical implementation. We retrospectively investigated n = 52 patients who received 919 ECT sessions with S-ketamine plus propofol as anaesthetic agents. Several anaesthesia and ECT-related parameters including doses of S-ketamine and propofol were analysed. The mean empirically determined S-ketamine/propofol ratio was 1.38 (SD ± 0.57) for 919 individual ECT sessions and 1.52 (SD ± 0.62) for 52 patients, respectively. The mean relative dose was 0.72 (± 0.18) mg/kg S-ketamine and 0.54 (± 0.21) mg/kg propofol. Higher propofol dose was associated with poorer seizure quality. Seizure quality and time in recovery room were significantly influenced by age. Ketofol could be an option to exploit the advantageous qualities of S-ketamine and propofol, if both doses are reduced compared with single use of S-ketamine or propofol. Patients with poor seizure quality may benefit from lower propofol doses, which are applicable by the addition of ketamine. An empirically determined mixing ratio in favour of ketamine turned out to be preferable in a clinical setting. Recovery time was primarily prolonged by higher age rather than by ketamine dose, which had previously often been associated with a prolonged monitoring time in the recovery room. These new findings could improve electroconvulsive therapy and should be replicated in a prospective manner.

Duration of Electroconvulsive Therapy Postictal Burst Suppression Is Associated With Time to Reorientation.

INTRODUCTION: A burst suppression pattern in the electroencephalogram represents a down-regulated brain state, which also occurs in the postictal phase of electroconvulsive therapy (ECT). Suppressive actions of the brain to terminate the seizure are thought to be necessary for the efficacy of ECT. On the other hand, recent studies showed an association of burst suppression in general anesthesia or sedation with (postprocedural) cognitive complications. METHODS: We retrospectively examined the length of postictal burst suppression and reorientation time in 49 ECT sessions of 25 consecutive patients. Burst suppression duration was determined by bispectral index monitoring and defined as the time with a bispectral index value of less than 20%. The association between duration of burst suppression and reorientation time was analyzed with multivariate logistic and linear regression analysis controlling for several covariates. RESULTS: The reorientation time showed a statistically significant association with the duration of burst suppression, but with no other variable. Longer phase of postictal burst suppression predicted longer reorientation time in the recovery room (P = 0.046). CONCLUSIONS: The association between the duration of postictal burst suppression and reorientation time after ECT in this sample suggests that (not only the efficacy but also the) cognitive adverse effects of ECT might be related to the extent of postictal central inhibition after the termination of the seizure.

Persistent peri-Heptacene: Synthesis and In Situ Characterization.

n-peri-Acenes (n-PAs) have gained interest as model systems of zigzag-edged graphene nanoribbons for potential applications in nanoelectronics and spintronics. However, the synthesis of n-PAs larger than peri-tetracene remains challenging because of their intrinsic open-shell character and high reactivity. Presented here is the synthesis of a hitherto unknown n-PA, that is, peri-heptacene (7-PA), in which the reactive zigzag edges are kinetically protected with eight 4-tBu-C6 H4 groups. The formation of 7-PA is validated by high-resolution mass spectrometry and in situ FT-Raman spectroscopy. 7-PA displays a narrow optical energy gap of 1.01 eV and exhibits persistent stability (t1/2 ≈25 min) under inert conditions. Moreover, electron-spin resonance measurements and theoretical studies reveal that 7-PA exhibits an open-shell feature and a significant tetraradical character. This strategy could be considered a modular approach for the construction of next-generation (3 N+1)-PAs (where N≥3).

Molecular parameters responsible for thermally activated transport in doped organic semiconductors.

Doped organic semiconductors typically exhibit a thermal activation of their electrical conductivity, whose physical origin is still under scientific debate. In this study, we disclose relationships between molecular parameters and the thermal activation energy (EA) of the conductivity, revealing that charge transport is controlled by the properties of host-dopant integer charge transfer complexes (ICTCs) in efficiently doped organic semiconductors. At low doping concentrations, charge transport is limited by the Coulomb binding energy of ICTCs, which can be minimized by systematic modification of the charge distribution on the individual ions. The investigation of a wide variety of material systems reveals that static energetic disorder induced by ICTC dipole moments sets a general lower limit for EA at large doping concentrations. The impact of disorder can be reduced by adjusting the ICTC density and the intramolecular relaxation energy of host ions, allowing an increase of conductivity by many orders of magnitude.

Insight into doping efficiency of organic semiconductors from the analysis of the density of states in n-doped C60 and ZnPc.

Doping plays a crucial role in semiconductor physics, with n-doping being controlled by the ionization energy of the impurity relative to the conduction band edge. In organic semiconductors, efficient doping is dominated by various effects that are currently not well understood. Here, we simulate and experimentally measure, with direct and inverse photoemission spectroscopy, the density of states and the Fermi level position of the prototypical materials C60 and zinc phthalocyanine n-doped with highly efficient benzimidazoline radicals (2-Cyc-DMBI). We study the role of doping-induced gap states, and, in particular, of the difference Δ1 between the electron affinity of the undoped material and the ionization potential of its doped counterpart. We show that this parameter is critical for the generation of free carriers and influences the conductivity of the doped films. Tuning of Δ1 may provide alternative strategies to optimize the electronic properties of organic semiconductors.

Susceptibility of BAFF-var allele carriers to severe SLE with occurrence of lupus nephritis.

BACKGROUND: Dysregulation of the B-cell activating factor (BAFF) system is involved in the pathogenesis of systemic lupus erythematosus (SLE). Increased serum concentrations of BAFF are related to lupus nephritis and disease activity among SLE patients. Recently, a variant of the BAFF-encoding gene, BAFF-var, was identified to be associated with autoimmune diseases, in particular SLE, and to promote the production of soluble BAFF. The present study aimed to assess the prevalence of BAFF-var in a cohort of 195 SLE patients and to analyze the association of the BAFF-var genotype (TNSF13B) with various manifestations of SLE. METHODS: A cohort of 195 SLE patients from Central Europe, including 153 patients from the Swiss SLE Cohort Study and 42 patients from the University Hospital Essen, Germany, underwent genotyping for detection of BAFF-var allele. RESULTS: Of the 195 patients, 18 (9.2%) tested positive for BAFF-var variant according to the minor allele frequency of 4.6%. The presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038) (p = 0.03 and p = 0.003). Among various organ manifestations of SLE, the presence of BAFF-var was associated with the occurrence of lupus nephritis (p = 0.038; odds ratio [OR], 2.4; 95% confidence interval [CI], 0.89-6.34) and renal activity markers such as proteinuria and hematuria (p = 0.03; OR, 2.4; 95% CI, 0.9-6.4 for proteinuria; p = 0.003; OR, 3.9; 95% CI, 1.43-10.76 for hematuria). SLE patients carrying the BAFF-var allele exhibited increased disease activity at study entry, as determined by the physician's global assessment (PGA: p = 0.002; OR, 4.8; 95% CI, 1.54-14.93) and the SLE Disease Activity Index (p = 0.012; OR, 3.5; 95% CI, 1.12-11.18). Consistent with that, the percentage of patients treated with immunosuppressive agents at study entry was higher among those carrying the BAFF-var allele than among those tested negative for BAFF-var (p = 0.006; OR, 3.7; 95% CI, 1.27-10.84). CONCLUSIONS: Our results indicate an association between the BAFF-var genotype and increased severity of SLE. Determining the BAFF-var status of SLE patients may improve the risk stratification of patients for whom the development of lupus nephritis is more likely and thus may be helpful in the follow-up care and treatment of SLE patients.