[The importance of microbiological results for the treatment of complicated appendicitis-a monocentric case-control study]. / Die Bedeutung mikrobiologischer Ergebnisse für die Therapie der komplizierten Appendizitis ­ eine monozentrische Fall-Kontroll-Studie.

BACKGROUND: Patients with complicated appendicitis frequently develop postoperative septic complications. There are no uniform standards for the choice of perioperative antibiotic prophylaxis and the duration of postoperative antibiotic treatment. The purpose of this study was to investigate associations between microbiological samples and postoperative complications. METHODS: Patients with appendectomy and positive intraoperative swabs during 2013-2018 were included in this case-control study. Pathogen classes and their resistance patterns were evaluated in initial and follow-up swabs and compared in each of the groups with and without complications. RESULTS: A total of 870 patients underwent surgery during the period studied. Pathogen detection succeeded in 102 of 210 cases (48.6%) with suspected bacterial peritoneal contamination. Conversion from laparoscopic to open intra-abdominal perforation and the presence of an abscess were independent risk factors for wound infections in the multivariate analysis. The combination of different classes of pathogens resulted in significantly increased overall resistance to ampicillin/sulbactam in both the initial swabs (57%) and the follow-up swabs (73%). Resistant E. coli strains combined with certain anaerobes were also regularly detected in postoperative intra-abdominal abscesses. Piperacillin/tazobactam was effective against 83% of positive swabs in our resistance tests. CONCLUSION: Surgical treatment for complicated appendicitis remains the central therapeutic column. A regular review of the existing resistance patterns in perforated appendicitis can help to adjust and improve antibiotic treatment. Piperacillin/tazobactam should be used cautiously as a reserve antibiotic. A valid alternative is second or third generation cephalosporins in combination with metronidazole.

Intestinal anastomotic healing models during experimental colitis.

BACKGROUND: Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease. METHODS: We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis. DISCUSSION: Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process. CONCLUSION: The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing.

Dicer regulates Nosema ceranae proliferation in honeybees.

Nosema ceranae is a microsporidian parasite that infects the honeybee midgut epithelium. The protein-coding gene Dicer is lost in most microsporidian genomes but is present in N. ceranae. By feeding infected honeybees with small interfering RNA targeting the N. ceranae gene coding Dicer (siRNA-Dicer), we found that N. ceranae spore loads were significantly reduced. In addition, over 10% of total parasite protein-coding genes showed significantly divergent expression profiles after siRNA-Dicer treatment. Parasite genes for cell proliferation, ABC transporters and hexokinase were downregulated at 3 days postinfection, a key point in the middle of parasite replication cycles. In addition, genes involved in metabolic pathways of honeybees and N. ceranae showed significant co-expression. Furthermore, the siRNA-Dicer treatment partly reversed the expression patterns of honeybee genes. The honeybee gene mucin-2-like showed significantly upregulation in the siRNA-Dicer group compared with the infection group continually at 4, 5 and 6 days postinfection, suggesting that the siRNA-Dicer feeding promoted the strength of the mucus barrier resulted from interrupted parasite proliferation. As the gene Dicer broadly regulates N. ceranae proliferation and honeybee metabolism, our data suggest the RNA interference pathway is an important infection strategy for N. ceranae.

Nanoscale Spin Manipulation with Pulsed Magnetic Gradient Fields from a Hard Disc Drive Writer.

The individual and coherent control of solid-state based electron spins is important covering fields from quantum information processing and quantum metrology to material research and medical imaging. Especially for the control of individual spins in nanoscale networks, the generation of strong, fast, and localized magnetic fields is crucial. Highly engineered devices that demonstrate most of the desired features are found in nanometer size magnetic writers of hard disk drives (HDD). Currently, however, their nanoscale operation in particular comes at the cost of excessive magnetic noise. Here, we present HDD writers as a tool for the efficient manipulation of single as well as multiple spins. We show that their tunable gradients of up to 100 µT/nm can be used to spectrally address individual spins on the nanoscale. Their gigahertz bandwidth allows one to switch control fields within nanoseconds, faster than characteristic time scales such as Rabi and Larmor periods, spin-spin couplings, or optical transitions, thus extending the set of feasible spin manipulations. We used the fields to drive spin transitions through nonadiabatic fast passages or to enable the optical readout of spin states in strong misaligned fields. Building on these techniques, we further apply the large magnetic field gradients for microwave selective addressing of single spins and show its use for the nanoscale optical colocalization of two emitters.

Microwave-Assisted Cross-Polarization of Nuclear Spin Ensembles from Optically Pumped Nitrogen-Vacancy Centers in Diamond.

The ability to optically initialize the electronic spin of the nitrogen-vacancy (NV) center in diamond has long been considered a valuable resource to enhance the polarization of neighboring nuclei, but efficient polarization transfer to spin species outside the diamond crystal has proven challenging. Here we demonstrate variable-magnetic-field, microwave-enabled cross-polarization from the NV electronic spin to protons in a model viscous fluid in contact with the diamond surface. Further, slight changes in the cross-relaxation rate as a function of the wait time between successive repetitions of the transfer protocol suggest slower molecular dynamics near the diamond surface compared to that in bulk. This observation is consistent with present models of the microscopic structure of a fluid and can be exploited to estimate the diffusion coefficient near a solid-liquid interface, of importance in colloid science.

Perineal herniation of an ileal neobladder following radical cystectomy and consecutive rectal resection for recurrent bladder carcinoma.

Secondary perineal herniation of intraperitoneal contents represents a rare complication following procedures such as abdominoperineal rectal resection or cystectomy. We present a case of a perineal hernia formation with prolapse of an ileum neobladder following radical cystectomy and rectal resection for recurrent bladder cancer. Following consecutive resections in the anterior and posterior compartment of the lesser pelvis, the patient developed problems emptying his neobladder. Clinical examination and computed tomography revealed perineal herniation of his neobladder through the pelvic floor. Through a perineal approach, the hernial sac could be repositioned, and via a combination of absorbable and non-absorbable synthetic mesh grafts, the pelvic floor was stabilised. Follow-up review at one year after hernia fixation showed no signs of recurrence and no symptoms. In cases of extensive surgery in the lesser pelvis with associated weakness of the pelvic compartments, meshes should be considered for closure of the pelvic floor. Development of biological meshes with reduced risk of infection might be an interesting treatment option in these cases.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

Wound repair: role of immune-epithelial interactions.

The epithelium serves as a highly selective barrier at mucosal surfaces. Upon injury, epithelial wound closure is orchestrated by a series of events that emanate from the epithelium itself as well as by the temporal recruitment of immune cells into the wound bed. Epithelial cells adjoining the wound flatten out, migrate, and proliferate to rapidly cover denuded surfaces and re-establish mucosal homeostasis. This process is highly regulated by proteins and lipids, proresolving mediators such as Annexin A1 protein and resolvins released into the epithelial milieu by the epithelium itself and infiltrating innate immune cells including neutrophils and macrophages. Failure to achieve these finely tuned processes is observed in chronic inflammatory diseases that are associated with non-healing wounds. An improved understanding of mechanisms that mediate repair is important in the development of therapeutics aimed to promote mucosal wound repair.

Abdominal aortic aneurysm screening: how many life years lost from underuse of the medicare screening benefit?

BACKGROUND: Since 2007, Medicare has provided one-time abdominal aortic aneurysm (AAA) screening for men with smoking history, and men and women with a family history of AAA as part of its Welcome to Medicare visit. OBJECTIVE: We examined utilization of the new AAA screening benefit and estimated how increased utilization could influence population health as measured by life years gained. Additionally, we explored the impact of expanding screening to women with smoking history. DESIGN: Analysis of Medicare claims and a simulation model to estimate the effects of screening, using published data for parameter estimates. SETTING: AAA screening in the primary care setting. PATIENTS: Newly-enrolled Medicare beneficiaries aged 65 years, with smoking history or family history of AAA. MAIN MEASURES: Life expectancy, 10-year survival rates. KEY RESULTS: Medicare data revealed low utilization of AAA screening, under 1% among those eligible. We estimate that screening could increase life expectancy per individual invited to screening for men with smoking history (0.11 years), with family history of AAA (0.17 years), and women with family history (0.08 years), and smoking history (0.09 years). Average gains of 131 life years per 1,000 persons screened for AAA compare favorably with the grade B United States Preventive Services Task Force (USPSTF) recommendation for breast cancer screening, which yields 95-128 life years per 1,000 women screened. These findings were robust over a range of scenarios. LIMITATIONS: The simulation results reflect assumptions regarding AAA prevalence, treatment, and outcomes in specific populations based on published research and US survey data. Published data on women were limited. CONCLUSIONS: The Welcome to Medicare and AAA screening benefits have been underutilized. Increasing utilization of AAA screening would yield substantial gains in life expectancy. Expanding screening to women with smoking history also has the potential for substantial health benefits.

Neutrophil-derived JAML inhibits repair of intestinal epithelial injury during acute inflammation.

Neutrophil transepithelial migration (TEM) during acute inflammation is associated with mucosal injury. Using models of acute mucosal injury in vitro and in vivo, we describe a new mechanism by which neutrophils infiltrating the intestinal mucosa disrupt epithelial homeostasis. We report that junctional adhesion molecule-like protein (JAML) is cleaved from neutrophil surface by zinc metalloproteases during TEM. Neutrophil-derived soluble JAML binds to the epithelial tight junction protein coxsackie-adenovirus receptor (CAR) resulting in compromised barrier and inhibition of wound repair, through decreased epithelial proliferation. The deleterious effects of JAML on barrier and wound repair are reversed with an anti-JAML monoclonal antibody that inhibits JAML-CAR binding. JAML released from transmigrating neutrophils across inflamed epithelia may thus promote recruitment of leukocytes and aid in clearance of invading microorganisms. However, sustained release of JAML under pathologic conditions associated with persistence of large numbers of infiltrated neutrophils would compromise intestinal barrier and inhibit mucosal healing. Thus, targeting JAML-CAR interactions may improve mucosal healing responses under conditions of dysregulated neutrophil recruitment.

Quantum error correction in a solid-state hybrid spin register.

Error correction is important in classical and quantum computation. Decoherence caused by the inevitable interaction of quantum bits with their environment leads to dephasing or even relaxation. Correction of the concomitant errors is therefore a fundamental requirement for scalable quantum computation. Although algorithms for error correction have been known for some time, experimental realizations are scarce. Here we show quantum error correction in a heterogeneous, solid-state spin system. We demonstrate that joint initialization, projective readout and fast local and non-local gate operations can all be achieved in diamond spin systems, even under ambient conditions. High-fidelity initialization of a whole spin register (99 per cent) and single-shot readout of multiple individual nuclear spins are achieved by using the ancillary electron spin of a nitrogen-vacancy defect. Implementation of a novel non-local gate generic to our electron-nuclear quantum register allows the preparation of entangled states of three nuclear spins, with fidelities exceeding 85 per cent. With these techniques, we demonstrate three-qubit phase-flip error correction. Using optimal control, all of the above operations achieve fidelities approaching those needed for fault-tolerant quantum operation, thus paving the way to large-scale quantum computation. Besides their use with diamond spin systems, our techniques can be used to improve scaling of quantum networks relying on phosphorus in silicon, quantum dots, silicon carbide or rare-earth ions in solids.

Hypoglycaemia and predisposing factors among clinical subgroups treated with intensive insulin therapy.

BACKGROUND: In previous studies, conflicting intensive insulin therapy (IIT) results have been observed, whereby IIT-related mortality seems to be lower in specific clinical subgroups. The aim of this study was to assess differences in glycaemic control, the risk of critical hypoglycaemia (≤ 2.2 mmol/l), the associated predisposing factors, and the in-hospital mortality in different clinical subgroups treated with IIT. METHODS: Prospective, observational study in a university-affiliated intensive care unit (ICU) conducted from 2004 to 2005. All patients (n = 1667) belonging to one of the six most common surgical intervention groups (cardiac, neuro, abdominal, vascular, orthopaedic, and spinal surgeries) and medical patients were included. IIT was performed with a target blood glucose level of 4.4-7.8 mmol/l. Different indices were analysed to evaluate glucose control and glycaemic variability. RESULTS: The rate of critical hypoglycaemia was significantly different within the different clinical subgroups and varied from 0.8% to 4.5%. Similar results were obtained for hyperglycaemia. Multivariable analyses for the predisposing factors of critical hypoglycaemia showed a heterogeneous distribution pattern among the different clinical subgroups. Similar results were obtained for the risk factors of in-hospital mortality. CONCLUSION: The risk of critical hypoglycaemia and the associated predisposing factors depended on the clinical subgroup involved. Critical hypoglycaemia is a potential threat for our patients, and the high risk of critical hypoglycaemia in some clinical subgroups appeared to reverse the benefits of IIT. As a result, it is crucial that the different subgroups involved in a study are defined to further interpret the potential benefits of IIT and the risk of critical hypoglycaemia.

High-precision nanoscale temperature sensing using single defects in diamond.

Measuring local temperature with a spatial resolution on the order of a few nanometers has a wide range of applications in the semiconductor industry and in material and life sciences. For example, probing temperature on the nanoscale with high precision can potentially be used to detect small, local temperature changes like those caused by chemical reactions or biochemical processes. However, precise nanoscale temperature measurements have not been realized so far owing to the lack of adequate probes. Here we experimentally demonstrate a novel nanoscale temperature sensing technique based on optically detected electron spin resonance in single atomic defects in diamonds. These diamond sensor sizes range from a micrometer down to a few tens of nanometers. We achieve a temperature noise floor of 5 mK/Hz(1/2) for single defects in bulk sensors. Using doped nanodiamonds as sensors the temperature noise floor is 130 mK/Hz(1/2) and accuracies down to 1 mK for nanocrystal sizes and therefore length scales of a few tens of nanometers. This combination of precision and position resolution, combined with the outstanding sensor photostability, should allow the measurement of the heat produced by chemical interactions involving a few or single molecules even in heterogeneous environments like cells.

Current status of laparoscopic surgery for patients with Crohn's disease.

PURPOSE: Minimally invasive surgery is increasingly utilized in treatment for refractory or complicated Crohn's disease, and new developments aim at further reducing the abdominal trauma and improving the outcome. This review evaluates current literature about minimally invasive surgery for patients with Crohn's disease, latest advances in single-incision surgery, and methods of specimen extraction. METHODS: Literature was reviewed with focus on the following topics: indications, surgical procedures, conversions, complications, and short- as well as long-term outcomes of laparoscopic compared to open surgery for refractory, complicated, and recurrent Crohn's disease. RESULTS: Short-term benefits such as shorter hospital stay and faster postoperative recovery are accompanied by long-term benefits such as better cosmetic results and lower treatment-associated morbidity. Single-incision surgery and minimally invasive methods of specimen extraction help to further reduce the surgical trauma and are gradually implemented in the treatment. CONCLUSION: In experienced centers, laparoscopic surgery for Crohn's disease is safe and as feasible as open operations, even for selected cases with operations for complicated or recurrent disease. However, accurate analysis of the data is complicated by the heterogeneity of clinical presentations as well as the variety of performed procedures. Additional long-term data are needed for evaluation of true benefits of the new techniques.

Quality-adjusted life years in cancer: pros, cons, and alternatives.

High and rising cancer treatment costs have forced a discussion about the use of cost-effectiveness analyses and other approaches to assess the value of cancer care. Oncologists have traditionally resisted using economic considerations in day-to-day medical considerations, though unavoidably their decisions have important resource implications, and increasingly economic realities are impacting their actions. In this paper, we summarise the use of the quality-adjusted life years to assess the value of cancer care and suggest potential ways to improve upon value measurement in cancer coverage and reimbursement decisions.

Influence of preparation form, luting space setting and cement type on the marginal and internal fit of CAD/CAM crown copings.

PURPOSE: To evaluate the influence of two different tooth preparation forms, two luting space settings and two cement types on the marginal and internal adaptation of all-ceramic crown copings produced using Cerec3 CAD/CAM system. MATERIALS AND METHODS: Forty working stone dies were made from two metal master casts (1. Tooth 36: with anatomic occlusal reduction, 2. Tooth 36: with flat occlusal reduction). Forty crown copings were milled using Vita In-Ceram 2000 YZ: 20 with an luting space settings of 0 = 100 microm and 20 with -50 = 50 microm. Copings were cemented using two cements (zinc phosphate cement, P21: Panavia21), then embedded and sectioned bucco-lingually and mesio-distally. Widths of marginal and internal gaps were measured using a light microscope at magnification of 40X. Data were submitted to one-way ANOVA, and statistical significance was set at p < 0.05. RESULTS: Copings with flat occlusal reduction and luting space settings of 100 pm had a better internal and marginal fit compared with copings with anatomic occlusal reduction and luting space settings of 50 microm, regardless of the cement used. P21 showed a significantly better fit compared with zinc phosphate cement. CONCLUSION: The presented Cerec3 CAD/CAM system can provide a marginal and internal adaptation which is comparable to that of conventional cast and conventional all-ceramic crowns.