Hospital volume and outcome in inguinal hernia repair: analysis of routine data of 133,449 patients.

INTRODUCTION: Inguinal hernias are repaired using either open or minimally invasive surgical techniques. For both types of surgery it has been demonstrated that a higher annual surgeon volume is associated with a lower risk of recurrence. This present study investigated the volume-outcome implications for recurrence operations, surgical complications, rate of chronic pain requiring treatment, and 30-day mortality based on the hospital volume. MATERIALS AND METHODS: The data basis used was the routine data collected throughout the Federal Republic of Germany for persons insured by the Local General Sickness Fund "AOK" who had undergone inpatient inguinal hernia repair between 2013 and 2015. Complications were recorded by means of indicators. Hospitals were divided into five groups on the basis of the annual caseload volume: 1-50, 51-75, 76-100, 101-125, and ≥ 126 inguinal hernia repairs per year. The effect of the hospital volume on the indicators was assessed using multiple logistic regression. RESULTS: 133,449 inguinal hernia repairs were included. The incidence for recurrence operations was 0.95%, for surgical complications 4.22%, for chronic pain requiring treatment 2.87%, and for the 30-day mortality 0.28%. Low volume hospitals (1-50 and 51-75 inguinal hernia repairs per year) showed a significantly increased recurrence risk compared to high volume hospitals with ≥ 126 inguinal hernia repairs per year (odds ratio: 1.53 and 1.24). No significant correlations were found for the other results. CONCLUSIONS: The study gives a detailed picture of hospital care for inguinal hernia repair in Germany. Furthermore, it was noted that the risk of hernia recurrence decreases in line with a rising caseload of the treating hospital.

Myelodysplastic syndromes without peripheral monocytosis but with evidence of marrow monocytosis share clinical and molecular characteristics with CMML.

MDS patients may present with monocytic marrow proliferation not fulfilling criteria for CMML. We analyzed MDS patients with or without a marrow monocytic proliferation by following up the amount of monocytic proliferation and characterizing their molecular profile. 315 MDS patients of Duesseldorf MDS registry were divided into two groups: A) 183 patients with monocytic esterase positive cells in marrow and monocytes between 101 and 900/µl in blood and B) 132 patients without monocytic esterase positive cells in marrow and monocytes in blood ≤100/µl. Twenty patients of each group were screened with regard to ASXL1, TET2, RUNX1, SETBP1, NRAS, and SRSF2 using Illumina myeloid panel. Group A patients were older, had significantly higher WBC, hemoglobin levels, neutrophils and platelets. CMML evolution rates were 4.9% and 1.5%, respectively (p=n.s.). TET2, NRAS and SRFS2 mutation frequencies were higher in group A and four patients had coexisting TET2 and SRFS2 mutation, which was shown to be characteristic but not specific for CMML. MDS patients with marrow monocytic proliferation have a more CMML-like pheno- and genotype and develop CMML more often. Those patients could potentially be very early stages of CMML or represent a CMML-like myeloid neoplasma with marrow adherence of the monocytic cell population.

Establishing an ICD-10 code based SARI-surveillance in Germany - description of the system and first results from five recent influenza seasons.

BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature.

The effect of peer review on mortality rates.

OBJECTIVE: Lowering of mortality rates in hospitals with mortality rates higher than accepted reference values for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia, stroke, mechanical ventilation (MV) and colorectal surgery by using an external peer review process that identifies areas requiring rectification and implements protocols directed at improving these areas. DESIGN: Retrospective, observational, quality management study using administrative data to compare in-hospital mortality rates (pre and post an external peer review process that included adoption of improvement protocols) with reference values. SETTING: German general hospitals of a large, private group. PARTICIPANTS: Hospitals with mortality rates higher than reference values. INTERVENTIONS: Peer review of medical records by experienced, outside physicians triggered by in-hospital mortality rates higher than expected. Inadequacies were identified, improvement protocols enforced and mortality rates subsequently re-examined. MAIN OUTCOME MEASURES: Mortality rates 1 year before and 1 year after peer review and protocol use. RESULTS: For AMI, CHF, pneumonia, stroke, MV and colorectal surgery, the mortality rates 1 year post-peer review were significantly decreased as compared to pre-peer review mortality rates. The standardized mortality ratio for all of the above diagnoses was 1.45, 1 year before peer review, and 0.97, 1 year after peer review. The absolute risk reduction of 7.3% translates into 710 deaths in this population which could have been prevented. CONCLUSIONS: Peer review triggered and conducted in the manner described here is associated with a significant lowering of in-hospital mortality rates in hospitals that previously had higher than expected mortality rates.

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.

Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

Refined medullary blast and white blood cell count based classification of chronic myelomonocytic leukemias.

Since 2001, chronic myelomonocytic leukemia (CMML) is classified by the WHO as myeloproliferative/myelodysplastic neoplasm. Herein we tried to better describe CMML patients with regard to hematological characteristics and prognosis using data of the Duesseldorf registry. We created 6 CMML subgroups, by dividing dysplastic and proliferative CMML at the cut-off of white blood cell count of 13,000/µL and splitting these two groups into 3 subgroups: CMML 0 with <5% blasts (n=101), CMML I with 5-9% blasts (n=204) and CMML II with 10-19% blasts (n=81). For comparison we included patients with RCMD, RAEB I and II. The newly created CMML 0 group had better prognosis than CMML I and II, median survival times were 31 months (ms), 19ms and 13ms, respectively (p<0.001). Median survival times between the corresponding dysplastic and proliferative subgroups 0 and 1 differed significantly: CMML 0 dysplastic 48ms and CMML 0 proliferative 17ms (p=0.03), CMML I dysplastic 29ms and CMML I proliferative 15ms (p=0.008), CMML II dysplastic 17ms and CMML II proliferative 10ms (p=0.09). Outcome of CMML patients worsens with increasing medullary blasts and when presenting as proliferative type. Therefore it is justified to separate CMML with <5% medullary blasts.

[10 years of Peer Reviewing: improving treatment by quality indicators from administrative data]. / 10 Jahre Peer Review - Verbesserung der medizinischen Behandlung durch Qualitätsindikatoren aus Routinedaten.

BACKGROUND AND OBJECTIVES: In-hospital mortality of myocardial infarction, heart failure and pneumonia within a private hospital chain were compared with the German average since 2000. METHODS: Increased in-hospital mortalities based on diagnosis coding with ICD-10 benchmarked with German average values induced peer reviews in concern hospitals. From 2000 until 2010, peer reviews as performed by at least 2 peers compared retrospectively case management and treatment with best care, classified the treatment and discussed it with responsible physicians. The classification consisted of category 1 for improvement potential, category 2 for miscoding and category 3 for sufficient treatment. Based on the improvement potential an operational plan of treatment improvement for the single hospital was produced which was to be realized by this hospital and supported by concern activities for knowledge improvement. RESULTS: In 2000, the indicators in-hospital mortality of myocardial infarction, heart failure and pneumonia of the hospital chain exceeded German average whereas in 2008 these values were lower (i. e. better) than German average. The peer reviews detected large improvement potentials in treatment processes and helped to improve them. CONCLUSION: Peer reviews as triggered by quality indicators supported improvement of treatment and likely outcomes.

Prevalence of dog erythrocyte antigen 1.1 in dogs in Switzerland evaluated with the gel column technique.

Canine blood typing has become an established and essential laboratory test due to the rising demand for safe and efficient blood transfusions. The most immunogenic and clinically important blood type is DEA 1.1. Little is known about DEA 1.1 frequencies or special characteristics among different canine breeds. 304 dogs were tested for DEA 1.1. DEA 1.1-typing was performed using a commercial gel column technique (ID-Gel Test Canine DEA 1.1, DiaMed, Cressier, Switzerland). Fifty-three percent of all tested dogs reacted positive for DEA 1.1, whereas 49 % of the mixed breeds tested DEA 1.1-positive. All Bernese mountain dogs (n = 22) and Rottweilers (n = 9) tested positive for DEA 1.1, while all Boxers (n = 8), Flat-Coated Retrievers (n = 9), and Border Collies (6) tested negative for DEA 1.1. The prevalence of DEA 1.1 in dogs in Switzerland was found to be comparable to that reported from other countries. The tested breeds were found to differ considerably in the frequency of DEA 1.1. This knowledge is useful for selection of blood donors. However, DEA 1.1 blood typing of donor and recipient prior to transfusion and cross matching in sensitized dogs is unavoidable.

Neonatal screening for biotinidase deficiency in Hungary: clinical, biochemical and molecular studies.

From 1989 to 2001, 1,336,145 newborns were screened for biotinidase deficiency in Hungary. Fifty-eight children with the disorder were identified as enzyme-deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.

Synthesis and biological activity of 7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF) and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

We recently described the syntheses of 12a-c, 4-amino-7-oxo substituted analogues of 5-deaza-5,6,7,8-tetrahydrofolic acid (5-DATHF), and 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), in six steps from commercially available p-substituted methyl benzoates in 20-27% overall yields. Such analogues were tested in vitro against CCRF-CEM leukemia cells and showed that they are completely devoid of any activity, the IC(50) being higher than 20 microg/mL for all cases. To clarify if the presence of the carbonyl group in position C7, the distinctive feature of our synthetic methodology, is the reason for this lack of activity, we have now obtained the 7-oxo substituted analogues of 5-DATHF and DDATHF, 18a-c, in 10-30% overall yield. Testing of 18a-c in vitro against CCRF-CEM leukemia cells revealed that these compounds are totally inactive. A molecular modeling study of 18b inside the active site of the complex E. coliGARTFase-5-DATHF-GAR pointed to an electronic repulsion between the atoms of the 7-oxo group and the carbonyl group of Arg90 as a possible explanation for the inactivity of 18a-c.

Solid phase vs. solution phase differential behavior: formation of a salicylate structure from a malondialdehyde moiety.

Treatment of 2, solid supported synthetic equivalent of 3-formylchromone (4), and ethyl acetoacetate affords the salicylate structure 8 instead of the previously reported isophtalate 7. This is the first formation of a salicylate by a double carbonyl condensation of a malondialdehyde moiety ever reported.

Decompensated strabismus after laser in situ keratomileusis.

We present a case of decompensated nerve IV palsy with vertical diplopia afer bilateral laser in situ keratomileusis. As the patient was given monovision, we believe diplopia occurred with a decrease in vision in 1 eye and interruption of fusion. Although corrective spectacles to restore equal vision at distance were prescribes, the patient needed a prism to eliminate her double vision. We suggest a careful cover/uncover test and versions assessment in all candidates for refractive surgery who want monovision correction and a full ocular motility evaluation if there is any doubt about binocular issues.

Nonsurgical management of binocular diplopia induced by macular pathology.

OBJECTIVE: To treat binocular diplopia secondary to macular pathology. METHODS: Seven patients underwent evaluation and treatment. All had constant vertical diplopia caused by various maculopathies, including subretinal neovascularization, epiretinal membrane, and central serous retinopathy. Visual acuity ranged from 20/20 to 20/30 in the affected eye. All except 1 patient had a small-angle, comitant hyperdeviation with no muscle paresis. Sensory evaluation demonstrated peripheral fusion and reduced stereoacuity. Neither prism correction nor manipulation of the refractive errors corrected the diplopia. A partially occlusive foil (Bangerter) of density ranging from 0.4 to 1.0 was placed in front of the affected eye to restore stable, single vision. RESULTS: The Bangerter foil eliminated the diplopia in all patients. Two patients elected not to wear the foil; 1 patient was afraid of becoming dependent, and the other was bothered by the visual blur. Visual acuity in the affected eye was reduced on average by 3 lines. All patients maintained the same level of sensory fusion, with only 2 having reduced stereoacuity. Symptoms returned when the foil was removed or its density was reduced. CONCLUSION: Low-density Bangerter foils provide an effective, inexpensive, and aesthetically acceptable management for refractory binocular diplopia induced by macular pathology, allowing peripheral fusion to be maintained.

Reasoning enantioselectivity and kinetics of seleno-subtilisin from the subtilisin template.

The active-site serine (Ser221) of subtilisin Carlsberg(from Bacillus licheniformis) and subtilisin BPN' (fromBacillus amyloliquefaciens) was chemically converted into a selenocystein. Contrary to subtilisin's protease activity the semisynthetic seleno-subtilisin catalyzed the reduction of hydroperoxides. Enantioselectivity and kinetics of this reaction were studied by kinetic resolution of five racemic alkyl aryl hydroperoxides catalyzed by the seleno-subtilisin variants. Due to the identical tertiary structure of subtilisin and seleno-subtilisin, the enzymes have comparable substrate binding properties. Thus, a rational screening for suitable peroxidase substrates featuring structural characteristics of known subtilisin substrates was enabled. The enantioselective recognition of (S)-configured alkyl aryl hydroperoxides by seleno-subtilisin was comprehensible by subtilisin's preference for comparable (S)-alkyl aryl amines or alcohols. The analysis of chiral products by multidimensional gas chromatography revealed enantiomeric excesses up to 98%. Kinetics of seleno-subtilisin were rationalized on the basis of the established substrate-catalyst interactions of the subtilisin framework. The Carlsberg and BPN' peroxidase variants revealed typical differences in turnover numbers (kcat) and Michaelis-Menten affinity constants (Km) already known from subtilisin variants. Turnover numbers of seleno-subtilisin BPN' were lower and Km values were higher in comparison to Carlsberg variant. Substrate affinity of several substituted 1-arylethyl hydroperoxides to seleno-subtilisin was reasonable in comparison to corresponding aryl boronic acid inhibitors of subtilisin.

Long-term treatment of type 2 diabetic patients with the new oral antidiabetic agent glimepiride (Amaryl): a double-blind comparison with glibenclamide.

An international, prospective, double-blind trial compared the long-term therapeutic value of glimepiride with glibenclamide in patients with Type 2 diabetes mellitus. Patients stabilised on glibenclamide were randomised to 1 mg glimepiride (524 patients) or 2.5 mg glibenclamide (520 patients). The treatment groups were comparable at baseline with respect to age (60.2 years), body mass index (26.5 kg/m2), duration of diabetes (5.0 years) and fasting blood glucose levels (163 mg/dl [9.0 mmol/l]). Doses were increased stepwise, up to 8 mg for glimepiride (once-daily) and 20 mg for glibenclamide (> 10 mg as divided dose), until metabolic control (fasting blood glucose < or = 150 mg/dl [8.3 mmol/l]), or maximum dose was achieved. After one year of treatment, patients entered a long-term follow-up study. Primary endpoints for evaluation of metabolic control, mean glycated haemoglobin and mean fasting blood glucose, were 8.4% and 174 mg/dl (9.7 mmol/l) for glimepiride and 8.3% and 168 mg/dl (9.3 mmol/l) for glibenclamide. Differences between treatment groups were not considered clinically relevant (95% confidence intervals (-0.05, 0.19%) for glycated haemoglobin and (2, 11 mg/dl) [0.1, 0.6 mmol/l] for fasting blood glucose). Statistically significant lower fasting insulin and C-peptide values were observed in glimepiride patients compared with glibenclamide (differences: insulin, -0.92 microU/ml [p = 0.04]; C-peptide, -0.14 ng/ml [p = 0.03]). Both treatment groups showed an equivalent safety profile. Adverse events were consistent with the nature of the diabetic patient population studied. Fewer hypoglycaemic reactions occurred with glimepiride than with glibenclamide (105 versus 150 episodes). The long-term follow-up (457 patients) confirmed that glimepiride (1-8 mg) once daily provides equivalent metabolic control to a higher dosage (2.5-20.0 mg) of glibenclamide. Both treatments were well tolerated.

New therapeutic uses for an old family of drugs: travels of a dental researcher from the lab to the university's office of technology transfer and beyond.

The authors, including an academic-inventor, the director of the University's tech-transfer office, and the CEO of a "start-up" pharmaceutical company based on the professor's (and his colleague's) inventions, relate the history and current status of their interactions. To start, the basic research leading to the "eureka" experiment (such things really do happen) is summarized: namely, the discovery of (i) the surprising ability of the tetracycline antibiotics to inhibit mammalian tissue-destructive proteinases (collagenase, gelatinase) during a variety of disease processes, e.g., periodontitis, the arthritides, osteopenia/osteoporosis, sterile corneal ulcers, tumor invasion/metastasis/angiogenesis, and (ii) a series of chemically-modified, non-antibacterial analogs of tetracyclines to inhibit these enzymes without producing typical antibiotic side effects. The role of the University in obtaining the services of patent attorneys, and its assistance in developing the strategy to deal with an industrial partner, is addressed. Above all, the authors stress the need for close cooperation and collegial interactions between all three groups in this high-risk (but potentially high-benefit-to-the-public) enterprise.

[Nanofiltration in production of Beriplex P/N: increasing the capacity of virus elimination while maintaining product quality]. / Nanofiltration bei der Herstellung von Beriplex P/N: Erhöhung der Kapazität zur Viruseliminierung unter Beibehaltung der Produktqualität.

For the manufacture of the PCC Beriplex P/N, nanofiltration was introduced into the production process of Beriplex HS providing an additional means to heat treatment for the clearance/inactivation of viruses. By nanofiltration, large enveloped viruses (HSV-1, HIV-1) were completely eliminated by a factor of more than 7 log10. While medium-sized enveloped viruses (HBV, BVDV) were cleared by a factor of approximately 4 log10, small non-enveloped viruses (poliovirus) were not removed. The product profile remained, no thrombogenic activities were detected.