Marienkrankenhaus Kassel

OBJECTIVE: The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor. BACKGROUND: Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations. METHODS: The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS. RESULTS: For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80-3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61-0.76), and high body mass index (BMI) (per kg/m increase, OR: 1.07, 95% CI: 1.04-1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71-0.78) after internal validation, and 0.78 (0.74-0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05). CONCLUSION: The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.

PURPOSE The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)–paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes. METHODS Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m 2 (after study amendment, 125 mg/m 2 ) or weekly sb-paclitaxel 80 mg/m 2 followed in both arms by four times epirubicin 90 mg/m 2 plus cyclophosphamide 600 mg/m 2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year. RESULTS A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease–free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m 2 compared with NAB-paclitaxel 150 mg/m 2 . CONCLUSION The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m 2 compared with NAB-paclitaxel 150 mg/m 2 .

This abridged version is based on an interdisciplinary guideline which corresponds to development stage 3 (S3) of guidelines according to the classification of the Association of the Scientific Medical Societies in Germany (AWMF). The guideline development process is characterized by the combination of formal evidence-search, formal consensus, logic (algorithms), decision and outcome analysis, and interdisciplinary development with the cooperation of 15 German and Austrian medical societies. [Table 1] shows the relationship between levels of evidence, consensus, and resulting recommendation grades of the recommendations of this guideline. The recommendation grades A – D are added to the recommendations in the abridged version. For the evidence levels, see the full version [1].

Measurements of beta-endorphin-like immunoreactivity have been performed in CSF and plasma of patients with schizophrenia and other neuropsychiatric disorders. The detection limit of the RIA was between 20--50 pg/ml (6--15 fmole/ml). In CSF the quantity of beta-endorphin-like immunoreactivity ranges up to 65 pg/ml. The data from schizophrenics and other neuropsychiatric patients show no obvious deviation from the results in a control group of medical patients with normal CSF findings. In plasma the immunoreactive beta-endorphin-like material ranges up to 250 pg/ml. There is only a small tendency to higher values in schizophrenic patients, if compared with different types of neuroses and affective and organic psychoses. In a second series of experiments also this tendency could not be reproduced. In 9 electroconvulsive treatments an increase of blood beta-endorphin-like immunoreactivity was observed 7 times. A possible endorphinergic mechanism in the mode of action of electroconvulsion is hypothesized.

Cardiovascular autonomic diabetic neuropathy (CADN) is one of the most common diabetes-associated complications. Disturbed heart rate variability (HRV) is very often the earliest symptom, even in clinically asymptomatic patients. The following article offers a topical overview for those working or interested in the fields of diabetology and cardiology.

This study was designed to trace bone marrow-derived stromal cells (MSC) after implantation in an ectopic rat model of bone tissue engineering. MSC were isolated from adult donor rats, expanded, seeded on a hydroxyapatite/β-tricalcium phosphate bone graft substitute (Straumann® BoneCeramic), and cultivated until confluent. Before subcutaneous implantation of seeded constructs and controls (unseeded bone graft substitute) in isogenic rats (n = 32), cells were labeled with the fluorescent dye carboxyfluoresceine-diacetate-succinimidyl-ester. Specimens were harvested at sacrifice on day 1, 3, 7, or 14 after implantation (n = 8 per group) and processed for histology (hematoxylin and eosin, CD68, 4',6-diamidino-2-phenylindol). Carboxyfluoresceine-diacetate-succinimidyl-ester-labeled transplanted cells were quantified in decalcified sections (50 fields of view per specimen) at 488 nm. Over time, transplanted cells decreased in number from 31.3 ± 2.3 (day 1) to 9.2 ± 1.1 (day 3) and 0.3 ± 0.1 (day 7) (p < 0.001). Fourteen days postimplantation MSC could no longer be identified. Additionally, starting on day 3 postimplantation, cellular disintegration was noted. Multinucleated giant cells were present in constructs and controls on day 7 and increased to day 14 postimplantation. These results indicate that ectopically transplanted MSC survive for a rather short time after implantation. Possible reasons for early cell death are discussed.

Dear International Journal of Implant Dentistry reader, Is there a place for a new electronic open access journal in implant dentistry?

BACKGROUND: Diaphragmatic dysfunction is an important reason for dyspnea in COPD patients. But diaphragmatic dysfunction is difficult to evaluate. Ultrasound is an option. We measure sonographically the up- and downward movement of the lung silhouette on both hemidiaphragms. The aim of this prospective investigation was to compare this method with another sonographic method that visualizes the right hemidiaphragm directly and to compare the sonographic results with lung function parameters. METHODS AND PATIENTS: Eighty participants - 20 healthy persons and 60 COPD patients - three groups each with 20 patients with COPD GOLD II, III, and IV - were investigated. The sonographic measurements of the diaphragms were performed. Lung function parameters, blood gases, and 6-minute walk test were also collected and compared to the sonographic results. RESULTS: The sonographic measurement of the lung silhouette was easy to perform in all study participants. The correlation between the sonographic methods measuring the right hemidiaphragmatic movement was strong (r=0.85). There was also a strong correlation between the demonstrated sonographic measurement of the up- and downward movement of the lung silhouette and the forced expiratory volume in the first second (r=0.83). CONCLUSION: We demonstrated that the sonographic measurement of the movement of the lung silhouette is an easy way to establish diaphragmatic dysfunction in COPD patients; it can be done in all patients with reliable results for the right and the left hemidiaphragm.

BACKGROUND: The acromioclavicular joint (ACJ) is one of the more common sites of shoulder girdle injury, accounting for 4-12% of all such injuries, with an incidence of 3-4 cases per 100 000 persons per year in the general population. Current topics of debate include the proper standard diagnostic evaluation, the indications for surgery, and the best operative method. METHODS: This review is based on publications retrieved by a selective literature search. RESULTS: Mechanical trauma of the ACG can tear the ligamentous apparatus that holds the acromion, clavicle, and coracoid process together. Different interventions are indicated depending on the nature of the injury. In recent years, the horizontal component of the instability has received more attention, in addition to its vertical component. Persistent instability can lead to chronic, painful limitation of shoulder function, particularly with respect to working above the head. Surgical stabilization is therefore recommended for high-grade instability of Rockwood types IV and V. Modern reconstruction techniques enable selective vertical and horizontal treatment of the instability and have been found superior to traditional methods, particularly in young athletes. Arthroscopic techniques are advantageous because they are less invasive, do not require removal of implanted material, and afford the opportunity to diagnose any accompanying lesions definitively and to treat them if necessary. Surgery for acute injuries should be performed within three weeks of the trauma. For chronic injuries, additional tendon augmentation is now considered standard treatment. CONCLUSION: High-grade ACJ instability is a complex and significant injury of the shoulder girdle that can cause persistent pain and functional impairment. The state of the evidence regarding its optimal treatment is weak. Large-scale, prospective, randomized comparative studies are needed in order to define a clear standard of treatment.

Background: Despite the encouraging results of noninvasive ventilation (NIV) in chronic hypercapnic COPD patients, it is also evident that some patients do not tolerate NIV or do not benefit from it. We conducted a study in which COPD patients with stable, chronic hypercapnia were treated with NIV and nasal high-flow (NHF) to compare effectiveness. Methods: In a multi-centered, randomized, controlled, cross-over design, patients received 6 weeks of NHF ventilation followed by 6 weeks of NIV ventilation or vice-versa (TIBICO) between 2011 and 2016. COPD patients with stable daytime hypercapnia (pCO 2 ≥50 mmHg) were recruited from 13 German centers. The primary endpoint was pCO 2 changes from baseline blood gas, lung function, quality of life (QoL), the 6 min walking test, and duration of device use were secondary endpoints. Results: A total of 102 patients (mean±SD) age 65.3±9.3 years, 61% females, body mass index 23.1±4.8 kg/m, 2 90% GOLD D, pCO 2 56.5±5.4 mmHg were randomized. PCO 2 levels decreased by 4.7% (n=94; full analysis set; 95% CI 1.8–7.5, P =0.002) using NHF and 7.1% (95% CI 4.1–10.1, P <0.001) from baseline using NIV (indistinguishable to intention-to-treat analysis). The difference of pCO 2 changes between the two devices was −1.4 mmHg (95% CI −3.1–0.4, P =0.12). Both devices had positive impact on blood gases and respiratory scores (St. George’s Respiratory Questionnaire, Severe Respiratory Insufficiency Questionnaire). Conclusions: NHF may constitute an alternative to NIV in COPD patients with stable chronic hypercapnia, eg, those not tolerating or rejecting NIV with respect to pCO 2 reduction and improvement in QoL. Keywords: noninvasive ventilation, nasal high-flow, COPD, hypercapnia A Letter to the Editor has been published for this article. A Response to Letter has been published for this article.

Zusammenfassung. Auf der Basis von 11 700 Enzym-Aktivitäts-Bestimmungen im Serum von 1500 Patienten mit verschiedenen Leber-Erkrankungen werden Möglichkeiten und Grenzen der «Enzym-Diagnostik» im Rahmen bewährter klinischer Untersuchungsmethoden für Diagnose und Differentialdiagnose der Leber-Erkrankungen besprochen und die praktische Bedeutung der Aufstellung eines «Funktions-Musters» begründet.

Although theoretical assumptions and empirical evidence suggest an association between borderline personality disorder (BPD) and antisocial behavior or even antisocial personality disorder (APD), there is no study relating the psychodynamic aspects of BPD to antisocial behavior. In this study, the authors tested the correlation between the structural criteria of borderline personality organization (BPO)--that is, identity diffusion, primitive defense mechanisms, and reality testing--and antisocial features, neuroticism, and interpersonal problems. A sample of imprisoned violent offenders (N = 91) was studied using the Antisocial Personality Questionnaire (APQ), the Borderline Personality Inventory (BPI), the Neo-Five-Factor-Inventory (Neo-FFI), and the Inventory of Interpersonal Problems (IIP). Significant correlations were predicted and found between the BPI scales of identity diffusion, primitive defense mechanisms, impaired reality testing, and fear of closeness and antisocial features, neuroticism, agreeableness, and interpersonal problems. The results are consistent with both object relations theory and attachment theory.

Objective: The formerly observed volume–outcome relation for percutaneous coronary interventions (PCIs) has recently been questioned. Design: We analysed data of the PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte. Patients: In 2003 a total of 27 965 patients at 67 hospitals were included. Results: The median PCI volume per hospital was 327. In-hospital mortality was 1.85% in hospitals belonging to the lowest PCI volume quartile and 1.21% in the highest quartile (p for trend &lt;0.001). Two groups of patients were then compared according to their treatment at hospitals with either &lt;325 PCIs (n = 5754) or &gt;325 PCIs (n = 22 211) per year. Logistic regression analysis showed that a PCI performed at hospitals with a volume of &gt;325 PCI/year was independently associated with a lower hospital mortality (OR = 0.67, 95% CI: 0.52 to 0.87; p = 0.002). If PCI was performed in patients with acute myocardial infarction there was a significant decline in mortality with increasing volume (p for trend = 0.004); however, there was no association in patients without a myocardial infarction. Conclusions: This analysis of contemporary PCI in clinical practice shows a small but significant volume–outcome relation for in-hospital mortality. However, this relation was only apparent in high-risk subgroups, such as patients presenting with acute myocardial infarction.

IMPORTANCE: The extent of changes in estradiol levels in male patients with hormone receptor-positive breast cancer receiving standard endocrine therapies is unknown. The sexual function and quality of life related to those changes have not been adequately evaluated. OBJECTIVE: To assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 2 randomized clinical trial assessed 56 male patients with hormone receptor-positive breast cancer. Patients were recruited from 24 breast units across Germany between October 2012 and May 2017. The last patient completed 6 months of treatment in December 2017. The analysis data set was locked on August 24, 2018, and analysis was completed on December 19, 2018. INTERVENTIONS: Patients were randomized to 1 of 3 arms: tamoxifen alone or tamoxifen plus gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) plus GnRHa for 6 months. MAIN OUTCOMES AND MEASURES: The primary end point was the change in estradiol levels from baseline to 3 months. Secondary end points were changes of estradiol levels after 6 months, changes of additional hormonal parameters, adverse effects, sexual function, and quality of life after 3 and 6 months. RESULTS: In this phase 2 randomized clinical trial, a total of 52 of 56 male patients with a median (range) age of 61.5 (37-83) years started treatment. A total of 3 patients discontinued study treatment prematurely, 1 in each arm. A total of 50 patients were evaluable for the primary end point. After 3 months the patients' median estradiol levels increased by 67% (a change of +17.0 ng/L) with tamoxifen, decreased by 85% (-23.0 ng/L) with tamoxifen plus GnRHa, and decreased by 72% (-18.5 ng/L) with AI plus GnRHa (P < .001). After 6 months, median estradiol levels increased by 41% (a change of +12 ng/L) with tamoxifen, decreased by 61% (-19.5 ng/L) with tamoxifen plus GnRHa, and decreased by 64% (-17.0 ng/L) with AI plus GnRHa (P < .001). Sexual function and quality of life decreased when GnRHa was added but were unchanged with tamoxifen alone. CONCLUSIONS AND RELEVANCE: This phase 2 randomized clinical trial found that AI or tamoxifen plus GnRHa vs tamoxifen alone led to a sustained decrease of estradiol levels. The decreased hormonal parameters were associated with impaired sexual function and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01638247.

Autoimmune encephalitis (AE) can rarely manifest as a predominantly psychiatric syndrome without overt neurological symptoms. This study's aim was to characterize psychiatric patients with AE; therefore, anonymized data on patients with suspected AE with predominantly or isolated psychiatric syndromes were retrospectively collected. Patients with readily detectable neurological symptoms suggestive of AE (e.g., epileptic seizures) were excluded. Patients were classified as "probable psychiatric AE (pAE)," if well-characterized neuronal IgG autoantibodies were detected or "possible pAE" (e.g., with detection of nonclassical neuronal autoantibodies or compatible cerebrospinal fluid (CSF) changes). Of the 91 patients included, 21 (23%) fulfilled our criteria for probable (autoantibody-defined) pAE and 70 (77%) those for possible pAE. Among patients with probable pAE, 90% had anti-NMDA receptor (NMDA-R) autoantibodies. Overall, most patients suffered from paranoid-hallucinatory syndromes (53%). Patients with probable pAE suffered more often from disorientation (p < 0.001) and impaired memory (p = 0.001) than patients with possible pAE. Immunotherapies were performed in 69% of all cases, mostly with high-dose corticosteroids. Altogether, 93% of the patients with probable pAE and 80% of patients with possible pAE reportedly benefited from immunotherapies (p = 0.251). In summary, this explorative, cross-sectional evaluation confirms that autoantibody-associated AE syndromes can predominantly manifest as psychiatric syndromes, especially in anti-NMDA-R encephalitis. However, in three out of four patients, diagnosis of possible pAE was based on nonspecific findings (e.g., slight CSF pleocytosis), and well-characterized neuronal autoantibodies were absent. As such, the spectrum of psychiatric syndromes potentially responding to immunotherapies seems not to be limited to currently known autoantibody-associated AE. Further trials are needed.

506 Background: The efficacy and toxicity of olaparib in early BC pts with homologous DNA repair deficiency (here defined as HRD score high tumors +/- germline (g) or tumor (t) BRCA mutation) is not well described. GeparOLA investigates olaparib in HER2 negative early BC with HRD. Methods: GeparOLA (NCT02789332) randomized 102 pts to either paclitaxel 80 mg/m² weekly (Pw) plus olaparib 100 mg twice daily for 12 weeks (PwO n = 65) or Pw plus carboplatin (Cb) AUC2 weekly for 12 weeks (PwCb n = 37), both followed by EC. Randomization was stratified by hormone receptor-status (HR+ vs HR-) and age ( &lt; 40 vs ≥40 years). Pts with untreated primary cT2 - cT4a-d or cT1c with either cN+ or pNSLN+ or triple negative or Ki-67 &gt; 20% were included, with either g/t BRCA mutation and/or high HRD score. The primary endpoint is pathological complete response (pCR; ypT0/is ypN0). A one group χ2-test was planned to exclude the pCR rate of ≤55% in PwO→EC arm. Secondary endpoints are other pCR definitions, breast conservation rate, clinical and imaging response, tolerability and safety. Results: A total of 107 pts were randomized between 9/2016 and 7/2018; 106 started treatment. Median age was 47.0 years [range 25.0-71.0]; 36.2% of pts had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumors; G3: 86.8%; Ki-67 &gt; 20%: 89.6%; TNBC 72.6%; confirmed g /tBRCA 1/2 mutation: 60.4%. pCR rate with PwO was 55.1% (90%CI 44.5%-65.3%) vs PwCb 48.6% (90%CI 34.3%-63.2%). Analysis for the stratified subgroups showed higher pCR rates with PwO in the cohorts of pts &lt; 40 years and HR+ pts Clinical trial information: NCT02789332. Conclusions: GeparOla could not exclude a pCR rate of ≤55% in the PwO arm. Subgroup analysis is hypothesis generating and need further confirmation.[Table: see text]

OBJECTIVES: This study tested the feasibility of automatically detecting advanced sleep disordered breathing (SDB) from a pacemaker trans-thoracic impedance sensor. BACKGROUND: SDB is prevalent yet under-diagnosed in patients with cardiovascular disease. The potential for automated detection of SDB in patients receiving pacemakers with respiration sensors has not been fully explored. We hypothesized that the trans-thoracic impedance sensor could be utilized for automatic detection of advanced SDB. METHODS: Patients underwent overnight polysomnography (PSG). The pacemaker trans-thoracic impedance signal was simultaneously recorded and time synchronized with the polysomnograph. Cardiovascular health variables were abstracted from medical records. Apnea was defined as cessation of inspiratory airflow lasting 10 seconds or longer. Hypopnea was defined as a reduction of tidal volume of at least 30% from baseline tidal volume, lasting 10 seconds or more. A computer algorithm (PM-A) was developed to automatically detect SDB from the pacemaker impedance sensor data. The performance of automated SDB detection was compared against PSG. RESULTS: Sixty patients (aged 69 +/- 12 years, 45 males) were studied. Advanced SDB (moderate or severe) was diagnosed in 40 patients. Severe SDB (apnea-hypopnea index [AHI]> or = 30) was diagnosed in 32 patients (53%), but only 5 patients had prior diagnosis of the disease. Moderate SDB (30 > AHI > 15) was diagnosed in 8 patients of whom only two were previously diagnosed. Cardiovascular health variables did not predict the presence of advanced SDB. PM-A derived AHI correlated with that of the PSG (r = 0.80, P < 0.01). The algorithm identified patients with advanced SDB with 82% sensitivity and 88% specificity. CONCLUSIONS: It is feasible to automatically measure SDB severity using a pacemaker trans-thoracic impedance sensor. Advanced SDB was frequently undiagnosed in this cohort of pacemaker patients.

Objectives There is good scientific evidence that attention deficit hyperactivity disorder (ADHD) is both a predictor and a comorbidity of addictive disorders in adulthood. These associations not only focus on substance-related addictions but also on behavioral addictions like gambling disorder and Internet use disorder (IUD). For IUD, systematic reviews have identified ADHD as one of the most prevalent comorbidities besides depressive and anxiety disorders. Yet, there is a need to further understand the connections between both disorders to derive implications for specific treatment and prevention. This is especially the case in adult clinical populations where little is known about these relations so far. This study was meant to further investigate this issue in more detail based on the general hypothesis that there is a decisive intersection of psychopathology and etiology between IUD and ADHD. Methods Two case-control samples were examined at a university hospital. Adult ADHD and IUD patients ran through a comprehensive clinical and psychometrical workup. Results We found support for the hypothesis that ADHD and IUD share psychopathological features. Among patients of each group, we found substantial prevalence rates of a comorbid ADHD in IUD and vice versa. Furthermore, ADHD symptoms were positively associated with media use times and symptoms of Internet addiction in both samples. Discussion Clinical practitioners should be aware of the close relationships between the two disorders both diagnostically and therapeutically. When it comes to regain control over one's Internet use throughout treatment and rehabilitation, a potential shift of addiction must be kept in mind on side of practitioners and patients.

BACKGROUND: In 2014, we first described novel autoantibodies to the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1-IgG/anti-Sj) in patients with autoimmune cerebellar ataxia (ACA) in this journal. Here, we provide a review of the available literature on ITPR1-IgG/anti-Sj, covering clinical and paraclinical presentation, tumour association, serological findings, and immunopathogenesis. METHODS: Review of the peer-reviewed and PubMed-listed English language literature on ITPR1-IgG/anti-Sj. In addition, we provide an illustrative report on a new patient with ITPR1-IgG-associated encephalitis with cognitive decline and psychosis. RESULTS: So far, at least 31 patients with serum ITPR1-IgG/anti-Sj have been identified (clinical information available for 21). The most common manifestations were ACA, encephalopathy with seizures, myelopathy, and (radiculo)neuropathy, including autonomic neuropathy. In 45% of cases, an underlying tumour was present, making the condition a facultative paraneoplastic neurological disorder. The neurological syndrome preceded tumour diagnosis in all but one case. In most cases, immunotherapy had only moderate or no effect. The association of ITPR1-IgG/anti-Sj with manifestations other than ACA is corroborated by the case of a 48-year-old woman with high-titre ITPR1-IgG/anti-Sj antibodies and rapid cognitive decline, affecting memory, attention and executive function, and psychotic manifestations, including hallucinations, investigated here in detail. FDG-PET revealed right-temporal glucose hypermetabolism compatible with limbic encephalitis. Interestingly, ITPR1-IgG/anti-Sj mainly belonged to the IgG2 subclass in both serum and cerebrospinal fluid (CSF) in this and further patients, while it was predominantly IgG1 in other patients, including those with more severe outcome, and remained detectable over the entire course of disease. Immunotherapy with intravenous methylprednisolone, plasma exchange, and intravenous immunoglobulins, was repeatedly followed by partial or complete recovery. Long-term treatment with cyclophosphamide was paralleled by relative stabilization, although the patient noted clinical worsening at the end of each treatment cycle. CONCLUSIONS: The spectrum of neurological manifestations associated with ITPR1 autoimmunity is broader than initially thought. Immunotherapy may be effective in some cases. Studies evaluating the frequency of ITPR1-IgG/anti-Sj in patients with cognitive decline and/or psychosis of unknown aetiology are warranted. Tumour screening is essential in patients presenting with ITPR1-IgG/anti-Sj.

Eighty-eight asymptomatic carriers of hepatitis B surface antigen (HBsAg) were followed with biochemical, serologic, histologic, and immunohistologic studies over a period of four years. None of the 78 HBsAg carriers with normal or minimally changed liver tissue, antibody to hepatitis B e antigen (HBeAg) in serum, and no intranuclear hepatitis B core antigen (HBcAg) developed a chronic inflammatory liver disease. Four individuals lost circulatory HBsAg, and at least two individuals terminated their HBsAg carrier state. Seven asymptomatic HBsAg carriers with chronic hepatitis were characterized by HBeAg in serum and intranuclear HBcAg. However, three HBsAg carriers with chronic hepatitis and an absence of intrahepatocellular HBcAg were positive for antibody to HBeAg over the observation period. The mechanism that leads to chronic hepatitis in these patients remains to be determined.