Does glenohumeral offset affect clinical outcomes in a lateralized reverse total shoulder arthroplasty?

BACKGROUND: Reverse total shoulder arthroplasty (rTSA) exhibits high rates of success and low complication rates. rTSA has undergone numerous design adaptations over recent years, and lateralization of implant components provides theoretical and biomechanical benefits in stability and range of motion (ROM) as well as decreased rates of notching. However, the magnitude of implant lateralization and its effect on these outcomes is less well understood. The purpose of this study was to evaluate how increasing glenohumeral offset affects outcomes after rTSA, specifically in a lateralized humerus + medialized glenoid implant model. METHODS: Primary rTSA using a lateralized humeral + medialized glenoid implant model performed at a single academic institution between 2012 and 2018 were retrospectively reviewed. Patient-reported outcome (PRO) parameters and clinical outcomes including ROM were evaluated both pre- and postoperatively. Pre- and postoperative radiographs were analyzed for measurement of glenohumeral offset, defined as the acromial-tuberosity offset (ATO) distance on the anteroposterior radiograph. RESULTS: A total of 130 rTSAs were included in the analysis, with a mean follow-up of 35 mo. The mean postoperative absolute ATO was 16 mm, and the mean delta ATO (difference from pre- to postoperatively) was 4.6 mm further lateralized. Among all study patients, improvements in all ROM parameters and all PROs were observed from pre- to postoperative assessments. When assessing for the effects of lateralization on these outcomes, multivariate analysis failed to reveal a significant effect from the absolute postoperative ATO or the delta ATO on any outcome parameter. CONCLUSIONS: rTSA using a lateralized humeral + medialized glenoid implant model exhibits excellent clinical outcomes in ROM and PROs. However, the magnitude of lateralization as measured radiographically by the ATO did not significantly affect these outcomes; patients exhibited universally good outcomes irrespective of the degree of offset restoration.

Elevated BMI increases concurrent pathology and operative time in adolescent ACL reconstruction.

PURPOSE: The purpose of this study was to (1) report on the incidence of concurrent surgical pathology at the time of adolescent ACL reconstruction, (2) evaluate patient risk factors for concurrent pathology, and (3) measure the effect of BMI on operating room (OR) time. METHODS: A retrospective analysis of the NSQIP database for the years 2005-2017 was conducted. Nine-hundred and seventeen patients 18 years of age and younger who underwent ACL reconstruction (ACLR) were identified using CPT code 29888 and patients undergoing surgery for multi-ligamentous knee injuries were excluded. The mean patient age was 17.6 years (range 14-18, standard deviation 0.52) and consisted of 546 males (59.5%) and 371 females (40.5%). Logistic regression was used to assess the relationship between BMI and additional CPT codes for internal derangement at the time of surgery. Internal derangement was defined as any procedure for the treatment of a meniscal tear, chondral lesion, or loose body removal. Linear regression analysis was then performed to evaluate the effect of BMI on operative time. RESULTS: 43.7% of patients undergoing ACLR required an associated procedure for internal derangement. Additionally, the risk of requiring additional procedures for internal derangement increased by 3.1% per BMI point. BMI was also predictive of operative time, independent of the number of additional procedures. Specifically, the operative time increased by nearly one minute for every point increase in BMI (58.0 s). CONCLUSIONS: Adolescent patients with an elevated BMI were much more likely to require additional surgical procedures for internal derangement at the time of ACL reconstruction. Additionally, BMI was a significant predictor for longer operative times. LEVEL OF EVIDENCE: Level III.

Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

[Progressive renal insufficiency in a 55-year-old man with psoriasis]. / Progrediente Niereninsuffizienz bei einem 55-jährigen Patienten mit Psoriasis.

Treatment with tumor necrosis factor alpha (TNF-α) inhibitors is a well-established therapeutic strategy for various autoimmune diseases. However, little is known about renal complications and possible causality of renal injury due to this treatment. The following case of a patient with psoriasis demonstrates the difficulties in classifying renal complications of anti-TNF-α therapy versus kidney involvement caused by the underlying disease.

Engineering Vaccines to Reprogram Immunity against Head and Neck Cancer.

The recent Food and Drug Administration's approval of monoclonal antibodies targeting immune checkpoint receptors (ICRs) for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) offers exciting promise to improve patient outcome and reduce morbidities. A favorable response to ICR blockade relies on an extensive collection of preexisting tumor-specific T cells in the tumor microenvironment (TME). ICR blockade reinvigorates exhausted CD8+ T cells and enhances immune killing. However, resistance to ICR blockade is observed in about 85% of patients with HNSCC, therefore highlighting the importance of characterizing the mechanisms underlying HNSCC immune escape and exploring combinatorial strategies to sensitize hypoimmunogenic cold HNSCC to ICR inhibition. Cancer vaccines are designed to bypass the cold TME and directly deliver cancer antigens to antigen-presenting cells (APCs); these vaccines epitomize a priming strategy to synergize with ICR inhibitors. Cancer cells are ineffective antigen presenters, and poor APC infiltration as well as the M2-like polarization in the TME further dampens antigen uptake and processing, both of which render ineffective innate and adaptive immune detection. Cancer vaccines directly activate APC and expand the tumor-specific T-cell repertoire. In addition, cancer vaccines often contain an adjuvant, which further improves APC function, promotes epitope spreading, and augments host intrinsic antitumor immunity. Thus, the vaccine-induced immune priming generates a pool of effectors whose function can be enhanced by ICR inhibitors. In this review, we summarize the major HNSCC immune evasion strategies, the ongoing effort toward improving HNSCC vaccines, and the current challenges limiting the efficacy of cancer vaccines.

Noninvasive assessment and quantification of tumour vascularisation using MRI and CT in a tumour model with modifiable angiogenesis - An animal experimental prospective cohort study.

BACKGROUND: To investigate vascular-related pathophysiological characteristics of two human lung cancers with modifiable vascularisation using MRI and CT. METHODS: Tumour xenografts with modifiable vascularisation were established in 71 rats (approval by the Animal Care Committee was obtained) by subcutaneous transplantation of two human non-small-cell lung cancer (NSCLC) cells (A549, H1299) either alone or co-transplanted with vascular growth promoters. The vascularity of the tumours was assessed noninvasively by MRI diffusion-weighted-imaging (DWI), T2-weighted, and time-of-flight (TOF) sequences) as well as contrast-enhanced CT (CE-CT), using clinical scanners. As a reference standard, histological examinations (CD-31, fluorescent beads) were done after explantation. RESULTS: Microvessel density (MVD) was higher in co-transplanted tumours (171 ± 19 number/mm2) than in non-co-transplanted tumours (111 ± 11 number/mm2; p = 0.002). Co-transplanted tumours showed higher growth rates and larger tumour vessels at TOF-MRI as well as larger necrotic areas at CE-CT. In co-transplanted tumours, DWI revealed higher cellularity (lower minimal ADCdiff 166 ± 15 versus 346 ± 27 mm2/s × 10-6; p < 0.001), highly necrotic areas (higher maximal ADCdiff 1695 ± 65 versus 1320 ± 59 mm2/s × 10-6; p < 0.001), and better-perfused tumour stroma (higher ADCperf 723 ± 36 versus 636 ± 51 mm2/s × 10-6; p = 0.005). Significant correlations were found using qualitative and quantitative parameters: maximal ADCperf and MVD (r = 0.326); maximal ADCdiff and relative necrotic volume on CE-CT (r = 0.551); minimal ADCdiff and MVD (r = -0.395). CONCLUSIONS: Pathophysiological differences related to vascular supply in two human lung cancer cell lines with modifiable vascularity are quantifiable with clinical imaging techniques. Imaging parameters of vascularisation correlated with the results of histology. DWI was able to characterise both the extent of necrosis and the level of perfusion.

Inflammation, vitamin D and dendritic cell precursors in chronic kidney disease.

Decreased blood dendritic cell precursors (DCP) count is linked with atherosclerotic disease, while reduction of circulating DCP is also seen in patients with chronic kidney disease (CKD). As poor vitamin D status could be linked to a compromised innate immune response, we hypothesized that vitamin D status might be involved in the decrease in circulating DCP in CKD. Moreover, the potential role of inflammation was considered. Circulating myeloid (mDCP), plasmacytoid (pDCP) and total DCP (tDCP) were analysed using flow cytometry in 287 patients with CKD stage 3. Serum 25(OH)D and 1,25(OH)2D levels were measured using enzyme-linked immunosorbent assays (ELISA), interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α using cytometric bead array, C-reactive protein (CRP) using a high-sensitivity (hs) ELISA. Contrary to our hypothesis, there was no association between vitamin D levels and DCP, although their number was decreased significantly in CKD (P < 0·001). Instead, mDCP (r = -0·211) and tDCP (r = -0·188,) were associated slightly negatively with hsCRP but positively with the estimated glomerular filtration rate (eGFR, r = 0·314 for tDCP). According to multivariate linear regression, only higher hsCRP concentration and the presence of diabetes mellitus had a significant negative influence on DCP count (P < 0·03, respectively) but not vitamin D, age and eGFR. A significant impact of vitamin D on the reduction of circulating DCP in CKD 3 patients can be neglected. Instead, inflammation as a common phenomenon in CKD and diabetes mellitus had the main influence on the decrease in DCP. Thus, a potential role for DCP as a sensitive marker of inflammation and cardiovascular risk should be elucidated in future studies.

HbA1c and Age in Non-Diabetic Subjects: An Ignored Association?

Objective: Target HbA1c values given in the most National Therapeutic Guidelines for patients with diabetes and cut-off HbA1c values for diabetes diagnosis are usually not taking the age of the respective patients into account; despite the fact that an increase in HbA1c in subjects without diabetes with age is known for some time. In order to further quantify the association between age and HbA1c in non-diabetic subjects an analysis of one German register was performed. Methods: In this cross-sectional study we analyzed data from 7 699 visits of 2 921 patients without diabetes (age 46.6 y [range 18-93 y]; 69.1% women; BMI 27.6±6.4 kg/m²) who had at least one HbA1c and blood glucose measurement. Data were drawn from an electronic patient record system (EMIL™) in which data were collected between 01/1992 and 01/2014. The patients were divided in 6 age groups (< 30 years [n=1 057];>30-40 years [n=1 160];>40-50 years [n=1 693];>50-60 years [n=1 523];>60-70 years [n=1 310];>70 years [n=956]) and the HbA1c values of these groups were compared. Patients with: gestational diabetes, use of systemic glucocorticoids, malignant neoplasm, age<18 y at time of first visit and IGT were excluded. HbA1c measurements were DCCT adjusted. Results: Patients with age>70 years have a 0.47% [5.14 mmol/mol] higher HbA1c compared to those<30 years. The mean HbA1c of the age groups was:<30 4.98% [30.96 mmol/mol],>30-40 5.07% [31.99 mmol/mol],>40-50 5.17% [33.10 mmol/mol],>50-60 5.33% [34.79 mmol/mol],>60-70 5.42% [35.79 mmol/mol] and>70 years 5.45% [36.10 mmol/mol]. In a multiple linear model the regression coefficient for each year of age increase was ß=0.0074 (p<0.001); thus age results in an increase of 0.074% in HbA1c per decade. Conclusion: HbA1c increases significantly with ageing in people without diabetes. The use of different cut-off values for every age range for diagnosis of diabetes should be discussed.

MRI-imaging and clinical findings of eleven children with tick-borne encephalitis and review of the literature.

OBJECTIVES: The incidence of tick-borne encephalitis (TBE) is increasing in many countries. Magnetic resonance imaging (MRI) in the course of TBE is not regularly performed in children. The aim of our study was evaluating MRI-findings of children and adolescents with TBE. PATIENTS AND METHODS: Retrospective evaluation of the charts and MRIs of patients who had been treated for TBE in the four participating hospitals in the last twenty years. RESULTS: 11 patients (5 male; age at TBE 3 weeks-15 9/12 years; mean 104.9 months) were included. MRI (within the first week after admission) revealed symmetric or asymmetric T2-hyperintensities in both thalami in 7/11 patients with additional bilateral lesions in putamen and/or caudate nucleus in 3 patients, and additional cortical lesions in 2 patients. Our youngest patient presented with T2-hyperintensities affecting the whole left cerebral hemisphere including white and grey matter and both cerebellar hemispheres. One patient had a minimal reversible T2-hyperintensity in the splenium of the corpus callosum (RHSCC). 3/11 patients had a normal MRI. 4/11 patients showed complete neurological recovery (2/4 with a normal MRI, RHSCC patient). 6/11 children survived with significant sequelae: hemiparesis (n = 4); cognitive deficits (n = 4); pharmacoresistant epilepsy (n = 2). One patient died of a malignant brain edema. DISCUSSION: A spectrum of MRI findings can be found in children with TBE, often showing involvement of the subcortical deep grey matter structures. In children presenting with a meningoencephalitis and bilateral thalamic involvement TBE should be included in the differential diagnosis.

Recurrent High-Flow Arterio-Venous Malformation of the Thyroid Gland.

BACKGROUND: Vascular malformations and hemangiomas of the thyroid gland are rare disorders. The first case of a patient with recurrent high-flow arterio-venous malformation of the right thyroid gland involving the right endolarynx is presented. PATIENT FINDINGS: In June 2013, a 42-year-old female patient presented to the surgical department with recurrent hoarseness and a soft, vibrating mass on the right side of her neck. In 1993, she underwent right subtotal hemithyroidectomy with embolization on the day before surgery for a high-flow arterio-venous malformation of the thyroid gland. Diagnostic work-up in 2013 demonstrated a complex recurrent high-flow arterio-venous malformation on the right side of her neck involving the endolarynx. Full function of the right vocal fold could not be ascertained. The lesion was embolized again and excised the following day. Intraoperative gross bleeding and scar tissue prevented visualization and monitoring of the recurrent laryngeal nerve. Gross bleeding was also noted on hemithyroidectomy after embolization in 1993. No therapy was needed for the endolaryngeal part of the lesion. Histology showed large arterio-venous malformations with thyroid tissue. She remains well without signs of recurrence 18 month later but with a definitive voice handicap. SUMMARY: This is the first report of a recurrent high-flow arterio-venous malformation originally developing from the right thyroid gland involving the right endolarynx. Counseling, diagnostic, and therapeutic work-up of the patient was possible only with an interdisciplinary team. The endolaryngeal part of the hemangioma dried out after embolization and completion hemithyroidectomy. Her hoarseness has greatly improved but a definitive voice handicap remains. CONCLUSION: High-flow arterio-venous malformations of the thyroid gland are a rare disease, and recurrent lesions have not been reported. Interdisciplinary management of these patients is mandatory due to the complex nature of the underlying pathology. Recurrence might develop after long free intervals.

Complete evaluation of adrenal tumours in a tertiary care institution in Thuringia, Germany.

INTRODUCTION AND OBJECTIVE: Adrenal tumours, mainly incidentalomas, are an increasingly common clinical and diagnostic challenge. The aim of the present study was the retrospective evaluation of all patients with adrenal tumours treated in our university department from 1.1.1999-31.12.2013 PATIENTS AND METHODS: 187 patients (108 females: 79 males, mean age 57.7 years) were found to have adrenal tumours in our institution during the study period. All patients underwent basic and, when indicated, advanced analytical testing for hormonal activity. Tumours were classified according to patients' gender, age at diagnosis, tumour localization and size, as well as benignity and malignancy when postinterventional histopathological examination was conducted. RESULTS: 134 (71.7%) patients had non-hormone secreting tumours, 17 (9.1%) pheochromocytoma, 13 (7.0%) Conn-syndrome, 13 (7.0%) adrenal Cushing's disease, 1 congenital adrenal hyperplasia and 2 sexual hormone-secreting tumours. 7 (3.7%) tumours could not be definitively classified due to unclear or marginal test-results. Cushing's disease was more prevalent in females (11 females: 2 males). 163 (87.2% of the total cohort) tumours were unilateral [95 (50.8%) left; 68 (36.4%) right] and 24 (12.8%) were bilateral. Tumour size was <3 cm in 109 (58.3%), 3-6 cm in 63 (33.7%) and >6 cm in 15 (8.0%) patients. 60 (32.1%) patients underwent adrenalectomy, thereof 88.9% of the patients with hormonally active tumours, while 8 (4.3%) were evaluated with ultrasound-guided biopsy. Malignancy was confirmed in 10 individuals (5.3%; 3 non-functioning tumours, 3 pheochromocytomas, 2 Cushing's patients and 2 sexual-hormone secreting tumours), while 2 surgical specimens with histopathological diagnosis of pheochromocytoma showed signs of malignant changes. Benignity was histopathologically confirmed in 55 patients. CONCLUSIONS: The prevalence of detected adrenal tumours is rising due to widely available and applied abdominal imaging procedures. The vast majority of them are benign, of small size (<3 cm) and hormonally inactive. Adrenalectomy is the therapeutic method of choice in big and/or confirmed hormone-secreting tumours.

Evaluation of CD44 variant expression in oral, head and neck squamous cell carcinomas using a triple approach and its clinical significance.

Cancer stem cells possess the qualities of self-renewal, tumorigenesis and the ability to recapitulate a heterogeneous tumor. Our group was the first to isolate head and neck squamous cell carcinoma (HNSCC) stem cells using the cell surface marker CD44. CD44 is a trans-membrane glycoprotein with a multitude of key-functions that regulate cancer cell proliferation and metastasis. The variety of CD44 functions is due to tissue-specific patterns of glycosylation of the extracellular portion, and to the multiple protein isoforms (CD44 variants, CD44v) generated by alternative splicing. This study investigates the expression pattern of CD44 variants in HNSCC. Ten cell lines from the most common HNSCC locations and representative of various clinical outcomes were assayed by quantitative realtime PCR, flow cytometry and immunofluorescence comparatively with normal oral keratinocytes. The CD44 v4 and v6 were exclusively abundant in HNSCC while the isoform v1,2 was expressed in normal oral keratinocytes. Of interest, the highest level of CD44v6 expression was detected in advanced metastatic HNSCC, suggesting a link between CD44v6 expression and HNSCC metastasis, while the highest CD44v4 was detected in a stage IV HNSCC refractory to chemotherapy which developed recurrence. Oral-derived HNSCC expressed the highest CD44v4 and v6, and levels corresponded with staging, showing also an increasing tendency with recurrence and metastasis. CD44v were detected predominantly in smaller cells (a characteristic that has been associated with stem cell properties) or cells with mesenchymal morphology (a characteristic that has been associated with the migratory and invasive potential of epithelial tumor cells), suggesting that CD44v differential expression in HNSCC may be representative of the morphological changes inherent during tumor progression towards a more aggressive potential, and thus contributing to the individual tumor biology. The mechanism of CD44 variant involvement in HNSCC progression and metastasis is under investigation.

[Joint swelling, reversible arm paresis, and elevated serum IgG4 in a 55-year-old man]. / Gelenkschwellungen, reversible Armparese und erhöhtes Serum-IgG4 bei einem 55-jährigen Patienten.

Only described in the last 10 years, IgG4-related disease is a fibroinflammatory disorder characterized by tumorous lesions with dense lymphoplasmacytic infiltration by IgG4-positive plasma cells and often elevated concentration of serum IgG4. In this paper, we present a male patient with this disease involving the lymph nodes and possibly the joints and kidneys. Infiltration of lymph node tissue with IgG4-positive plasma cells was demonstrated. The general condition of the patient improved considerably by immunosuppressive therapy.

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control.

UNLABELLED: Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD. INTRODUCTION: Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength. METHODS: In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated. RESULTS: Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score -0.76 ± 0.94 vs. -0.23 ± 1.02; p = 0.031) and total hip (z-score -0.54 ± 0.93 vs. 0.11 ± 1.11; p = 0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1 ± 53.6 vs. 133.2 ± 40.4; p = 0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95% CI 1.00-1.03/pmol/ml increase of pentosidine; p = 0.008 and odds ratio 1.93, 95% CI 1.16-3.20 per percentage increase of HbA1c; p = 0.011). CONCLUSIONS: The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.

[Psychopharmacological treatment of patients in a university department of internal medicine]. / Therapie mit Psychopharmaka bei internistischen Patienten einer Universitätsklinik.

BACKGROUND AND OBJECTIVE: Psychotropic drugs are among the most widely prescribed drugs. We aimed to systematically analyze the use of psychotropic drugs among inhospital patients in a large university department of internal medicine. METHODS: All discharge letters from the Department of Internal Medicine III, University Hospital Jena, Germany, in the year 2010 were retrospectively screened for the use of psychotropic drugs. Metabolic parameters, blood pressure and blood counts were compared to those of a control group; psychiatric diagnoses and consultation of a psychiatrist were noted. RESULTS: Data from 2160 patients were examined (54.5% female, 45,5% male). In 371 patients (17.2%, 63.3% female, 36.4% male) the prescription of psychotropic drugs was recorded. The remaining 1789 patients without psychotropic drugs were used as control group. Patients with psychotropic drugs were significantly older (median 69 vs. 61 years) and more frequently female (p < 0.001). The most frequently used drug group were antidepressants. Both obesity (43.3 vs. 32.3%) and cachexia (9.1 vs. 2.8%) were significantly more common in the psychotropic drug group (p < 0.001). There were also more patients with diabetes (p < 0.001), but their HbA1c levels were not different from the control group. In 44.5% of the patients no psychiatric diagnosis was noted, in only 14.5% a psychiatrist had been consulted. Rather frequently (10% of patients) therapy with benzodiazepine receptor agonists or benzodiazepines was mentioned in the discharge letters. CONCLUSION: The indication for psychotropic drug use could not be reproduced exactly in each case. Psychiatric diagnoses lacked in a substantial part of cases. As to the rest, affective disorders and organic mental disorders were rather frequent indications. Closer interdisciplinary cooperation between internists and psychiatrists is recommended to improve psychotropic drug therapy in older, often multimorbid patients in internal medical wards.

Hairy cell leukemia: short review, today's recommendations and outlook.

Hairy cell leukemia (HCL) is part of the low-grade non-Hodgkin lymphoma family and represents approximately 2% of all leukemias. Treatment with splenectomy and interferon-α historically belonged to the first steps of therapeutic options, achieving partial responses/remissions (PR) in most cases with a median survival between 4 and 6 years in the 1980s. The introduction of the purine analogs (PA) pentostatin and cladribine made HCL a well-treatable disease: overall complete response rates (CRR) range from 76 to 98%, with a median disease-free survival (DFS) of 16 years a normal lifespan can be reached and HCL-related deaths are rare. However, insufficient response to PA with poorer prognosis and relapse rates of 30-40% after 5-10 years of follow-up may require alternative strategies. Minimal residual disease can be detected by additional examinations of bone marrow specimens after treatment with PA. The use of immunotherapeutic monoclonal antibodies (mAB) like rituximab as a single agent or in combination with a PA or more recently clinical trials with recombinant immunotoxins (RIT) show promising results to restrict these problems. Recently, the identification of the possible disease-defining BRAF V600E mutation may allow the development of new therapeutic targets.

Endoscopically visualized lesions, histologic findings, and bacterial invasion in the gastrointestinal mucosa of dogs with acute hemorrhagic diarrhea syndrome.

BACKGROUND: Etiology of hemorrhagic gastroenteritis (HGE) syndrome in dogs is unknown and histopathologic and microbial investigations have only been performed post mortem. OBJECTIVE: To identify characteristic intra vitam endoscopic and histologic mucosal lesions, as well as bacterial species, within the mucosa of dogs with HGE. ANIMALS: Ten dogs diagnosed with HGE were included. Eleven dogs with gastroduodenoscopy and different intestinal diseases were used as controls for microbial changes. Dogs pretreated with antibiotics or diagnosed with any disease known to cause bloody diarrhea were excluded from the study. METHODS: In this prospective study, gastrointestinal biopsies were collected from 10 dogs with HGE. Endoscopic and histologic changes were assessed according to WSAVA guidelines. Biopsies from the stomach, duodenum, ileum, and colon were investigated by histology and by immunohistochemistry for the presence of Clostridium spp. and parvovirus. The first duodenal biopsy taken with a sterile forceps was submitted for bacterial culture. RESULTS: Acute mucosal lesions were only found in the intestines, not in the stomach. Clostridium spp., identified as Clostridium perfringens in 6/9 cases, were detected on the small intestinal mucosa in all dogs with HGE, either by culture or immunohistopathology. In the control group, C. perfringens could only be cultured in one of 11 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study demonstrate an apparent association between C. perfringens and the occurrence of acute hemorrhagic diarrhea. The term "HGE," which implies the involvement of the stomach, should be renamed as "acute hemorrhagic diarrhea syndrome."