Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter.

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.

Analysis of predictors for postoperative complications after pancreatectomy--what is new after establishing the definition of postpancreatectomy acute pancreatitis (PPAP)?

PURPOSE: We aimed to analyze the predictive value of hyperamylasemia after pancreatectomy for morbidity and for the decision to perform rescue completion pancreatectomy (CP) in a retrospective cohort study. METHODS: Data were extracted from a retrospective clinical database. Postoperative hyperamylasemia (POH) and postoperative hyperlipasemia (POHL) were defined by values greater than those accepted as the upper limit at our institution on postoperative day 1 (POD1). The endpoints of the study were the association of POH with postoperative morbidity and the possible predictors for postpancreatectomy acute pancreatitis (PPAP) and severe complications such as the necessity for rescue CP. RESULTS: We analyzed 437 patients who underwent pancreaticoduodenectomy over a period of 7 years. Among them, 219 (52.3%) patients had POH and 200 (47.7%) had normal postoperative amylase (non-POH) levels. A soft pancreatic texture (odds ratio [OR] 3.86) and POH on POD1 (OR 8.2) were independent predictors of postoperative pancreatic fistula (POPF), and POH on POD1 (OR 6.38) was an independent predictor of rescue CP. The clinically relevant POPF (49.5% vs. 11.4%, p < 0.001), intraabdominal abscess (38.3% vs. 15.3%, p < 0.001), postoperative hemorrhage (22.8% vs. 5.1%, p < 0.001), major complications (Clavien-Dindo classification > 2) (52.5% vs. 25.6%, p < 0.001), and CP (13% vs. 1.8%, p < 0.001) occurred significantly more often in the POH group than in the non-POH group. CONCLUSION: Although POH on POD1 occurs frequently, in addition to other risk factors, it has a predictive value for the development of postoperative morbidity associated with PPAP and CP.

Evaluation of the inflammatory markers CCL8, CXCL5, and LIF in patients with anastomotic leakage after colorectal cancer surgery.

PURPOSE: Anastomotic leakage constitutes a dreaded complication after colorectal surgery, leading to increased morbidity and mortality as well as prolonged hospitalization. Most leakages become clinically apparent about 8 days after surgery; however, early detection is quintessential to reduce complications and to improve patients' outcome. We therefore investigated the significance of specific protein expression profiles as putative biomarkers, indicating anastomotic leakage. METHODS: In this single-center prospective cohort study serum and peritoneal fluid samples-from routinely intraoperatively inserted drainages-of colorectal cancer patients were collected 3 days after colorectal resection. Twenty patients without anastomotic leakage and 18 patients with an anastomotic leakage and without other complications were included. Protein expression of seven inflammatory markers in serum and peritoneal fluid was assessed by multiplex ELISA and correlated with patients' clinical data. RESULTS: Monocyte chemoattractant protein 2 (CCL8/MCP-2), leukemia-inhibiting factor (LIF), and epithelial-derived neutrophil-activating protein (CXCL5/ENA-78) were significantly elevated in peritoneal fluid but not in serum samples from patients subsequently developing anastomotic leakage after colorectal surgery. No expressional differences could be found between grade B and grade C anastomotic leakages. CONCLUSION: Measurement 3 days after surgery revealed altered protein expression patterns of the inflammatory markers CCL8/MCP2, LIF, and CXCL5/ENA-78 in peritoneal fluid from patients developing anastomotic leakage after colorectal surgery. Further studies with a larger patient cohort with inclusion of different variables are needed to evaluate their potential as predictive biomarkers for anastomotic leakage.

Longstanding diplopia after ethmoidal artery ligation for epistaxis.

PURPOSE: In the rare case of intractable, posterior, non-sphenopalatine artery epistaxis, ligation of ethmoidal arteries using an external approach like a Lynch-type incision is required. Orbital complications, especially extra-ocular motility disorders with diplopia, are known, but in the literature rarely described. Our aim was to analyse the complication type, rate, and outcome of ethmoidal artery ligation for epistaxis. MATERIALS AND METHODS: Data between 2012 and 2017 of patients treated with ethmoidal artery ligation were analysed retrospectively and through a telephone interview using a non-standardized questionnaire. RESULTS: Data of 18 patients (m/f = 3/15) aged 53-83 years were reviewed. Epistaxis recurred in only one patient after 1 month. Five patients (28%) suffered from diplopia shortly after surgery. Motility analysis revealed full recovery with free motility in four out of five reported cases after 4-8 months, one patient still reports intermittent mild diplopia more than 1 year postoperatively. CONCLUSION: In patients with intractable, non-sphenopalatine artery epistaxis, anterior ethmoidal artery ligation was highly effective. Diplopia, however, occurred in one-third of our patient group. Information about motility restriction with longer standing diplopia are mandatory when consenting patients for ligation of ethmoidal arteries. Special care needs to be taken during dissection in the region of the trochlea and superior oblique muscle. LEVEL OF EVIDENCE: Case Series, level 4.

Antibiotic-resistant pathogens in different patient settings and identification of surveillance gaps in Switzerland - a systematic review.

The prevalence of antimicrobial resistance (AMR) varies significantly among different patient populations. We aimed to summarise AMR prevalence data from screening studies in different patient settings in Switzerland and to identify surveillance gaps. We performed a systematic review, searching Pubmed, MEDLINE, Embase (01/2000-05/2017) and conference proceedings for Swiss studies reporting on carbapenemase-producing Enterobacteriaceae (CPE), extended-spectrum beta-lactamases (ESBL), mobilised colistin-resistance, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) within different patient settings. We identified 2345 references and included 46 studies. For acute care patients, most screening data come from admission screenings, whereas AMR prevalence among hospitalised patients is largely unknown. Universal admission screenings showed ESBL-prevalences of 5-8% and MRSA-prevalences of 2-5%. For targeted screening, ESBL-prevalence ranged from 14-21%; MRSA-prevalence from 1-4%. For refugees, high ESBL (9-24%) and MRSA (16-24%) carriage rates were reported; returning travellers were frequently (68-80%) colonised with ESBL. Screening data for other pathogens, long-term care facility (LTCF) residents and pediatric populations were scarce. This review confirms high ESBL- and MRSA-carriage rates for risk populations in Switzerland. Emerging pathogens (CPE and VRE) and certain populations (inpatients, LTCF residents and children) are understudied. We encourage epidemiologists and public health authorities to consider these findings in the planning of future surveillance studies.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Late treatment failures in cerebrospinal fluid in patients on long-term maintenance ART with ritonavir-boosted protease PI monotherapy.

BACKGROUND: Antiretroviral treatment (ART) with ritonavir-boosted protease inhibitor monotherapy (rb-PMT) remains a potentially attractive strategy for treatment simplification in HIV-infected individuals. However, long-term follow-up in particular with respect to HIV-RNA suppression in cerebrospinal fluids (CSF) is still lacking. METHODS: Patients who participated in one of the three monotherapy trials [indinavir/r, ATARITMO (atazanavir/r), MOST (lopinavir/r)] at our HIV clinic and remained successfully suppressed during the entire trial (plasma < 50 copies/mL, CSF < 100 copies/mL) were offered to continue their monotherapy under close monitoring. While on rb-PMT, patients were asked to provide CSF samples in yearly or 2-yearly intervals. All patients fully suppressed in plasma and CSF for at least 12 months were included in the analysis. Patients demonstrating any failure in plasma or CSF resumed triple combined ART. RESULTS: A total of 27 patients (5 women and 22 men) fulfilled the entry criteria. The median follow-up time was 4.8 (1.1-10.9) years with an overall experience of 139 patient-years on monotherapy. Eleven of 27 (41 %) patients (2 women and 9 men) developed virologic failure (1 in plasma only, 4 in CSF only, 4 both in plasma and CSF and 2 in plasma with CSF not available). Plasma failure occurred in 7 patients after a median follow-up of 25 (13-32) months, and CSF failure in 8 patients after a median follow-up of 30 (14-64) months. Seven patients are still on rb-PMT with atazanavir/r. Failure was associated with shorter duration of fully suppressed plasma viral load prior to starting (p < 0.022). CONCLUSION: For selected patients, rb-PMT might be a valid long-term treatment strategy. Nevertheless, even after 12 months of full HIV-RNA suppression, more than 1/3 of patients may still develop failure in either plasma or CSF. Given the observation of isolated CSF failure, treatment monitoring with regular lumbar puncture should be recommended in rb-PMT. Only monotherapy with atazanavir/r was successful beyond 39 months. Monotherapy failure was significantly associated with a shorter duration of complete HIV-RNA suppression in plasma prior to rb-PMT start. Further investigation is needed to better identify predictors for patients that will qualify for successful long-term rb-PMT.

Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study.

BACKGROUND: Circulating tumour cells (CTC) in the blood have been accepted as a prognostic marker in patients with metastatic colorectal cancer (CRC). Only limited data exist on the prognostic impact of CTC in patients with early stage CRC using standardised detection assays. The aim of this study was to elucidate the role of CTC in patients with non-metastatic CRC. METHODS: A total of 287 patients with potentially curable CRC were enrolled, including 239 patients with UICC stage I-III. CTC were measured in the blood using the CellSearch system preoperatively and on postoperative days 3 and 7. The complete patient group (UICC I-IV) and the non-metastatic cohort (UICC I-III) were analysed independently. Patients were followed for 28 (0-53) months. Prognostic factors for overall and progression-free survival were analysed using univariate and multivariate analyses. RESULTS: CTC were detected more frequently in patients with metastatic disease. No clinicopathological variables were associated with CTC detection in non-metastatic patients. CTC detection (⩾1 CTC per 7.5 ml blood) in the blood was significantly associated with worse overall survival (49.8 vs 38.4 months; P<0.001) in the non-metastatic group (UICC I-III), as well as in the complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were the strongest prognostic factor in non-metastatic patients (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.3-13.6) as well as in the entire study group (HR 5.6; 95% CI 2.6-12.0). CONCLUSIONS: Preoperative CTC detection is a strong and independent prognostic marker in non-metastatic CRC.

Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases.

BACKGROUND: Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets. METHODS: Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay. RESULTS: We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases. CONCLUSION: Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.

Single chest drain is not inferior to double chest drain after robotic esophagectomy: a propensity score-matched analysis.

Background: Chest drain management has a significant influence on postoperative recovery after robot-assisted minimally invasive esophagectomy (RAMIE). The use of chest drains increases postoperative pain by irritating intercostal nerves and hinders patients from early postoperative mobilization and recovery. To our knowledge, no study has investigated the use of two vs. one intercostal chest drains after RAMIE. Methods: This retrospective cohort study evaluated patients undergoing elective RAMIE with gastric conduit pull-up and intrathoracic anastomosis. Patients were divided into two groups according to placement of one (11/2020-08/2022) or two (08/2018-11/2020) chest drains. Propensity score matching was performed in a 1:1 ratio, and the incidences of overall and pulmonary complications, drainage-associated re-interventions, radiological diagnostics, analgesic use, and length of hospital stay were compared between single drain and double drain groups. Results: During the study period, 194 patients underwent RAMIE. Twenty-two patients were included after propensity score matching in the single and double chest drain group, respectively. Time until removal of the last chest drain [postoperative day (POD) 6.7 ± 4.4 vs. POD 9.4 ± 2.7, p = 0.004] and intensive care unit stay (4.2 ± 5.1 days vs. 5.3 ± 3.5 days, p = 0.01) were significantly shorter in the single drain group. Overall and pulmonary complications, drainage-associated events, re-interventions, number of diagnostic imaging, analgesic use, and length of hospital stay were comparable between both groups. Conclusion: This study is the first to demonstrate the safety of single intercostal chest drain use and, at least, non-inferiority to double chest drains in terms of perioperative complications after RAMIE.

Humoral and cellular responses to mRNA-based COVID-19 booster vaccinations in patients with solid neoplasms under active treatment.

BACKGROUND: Patients with cancer are at high risk for severe coronavirus disease 2019 (COVID-19) infection. Knowledge regarding the efficacy of the messenger RNA (mRNA) vaccines in actively treated cancer patients is limited as they had been excluded from the pivotal studies of these vaccines. We evaluated humoral and cellular immune responses in cancer patients after double vaccination and a booster dose and identified disease- and treatment-related factors associated with a reduced immune response. We also documented the number and outcome of breakthrough infections. PATIENTS AND METHODS: Patients with metastatic solid malignancies undergoing active treatment were included if they had received two doses of the severe acute respiratory syndrome coronavirus 2 mRNA vaccines BNT162b2 or mRNA-1273 and a booster dose. Other causes of immunosuppression and previous COVID-19 infections (positive anti-nucleocapsid titers) were exclusion criteria. Anti-spike antibodies, neutralizing antibodies (nAbs) and T-cell responses were assessed about 6 months after the two-dose vaccination and 4 weeks after the booster. RESULTS: Fifty-one patients had pre-booster and 46 post-booster measurements. Anti-spike titers after two vaccine doses were highly variable and significantly lower in older patients, during treatment with chemotherapy compared to targeted and endocrine treatments and in patients with low CD4+ or CD19+ cell counts. The booster dose led to a significant increase in anti-spike antibodies and nAbs, achieving almost uniformly high titers, irrespective of baseline and treatment factors. The cellular immune response was also significantly increased by the booster, however generally more stable and not influenced by baseline factors and treatment type. Seventeen patients (33%) experienced breakthrough infections, but none required hospital care or died from COVID-19. CONCLUSIONS: An mRNA vaccine booster dose is able to increase humoral and cellular immune responses and to overcome the immunosuppressive influence of baseline and treatment factors in cancer patients. Breakthrough infections were uniformly mild in this vaccinated high-risk population.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.

[Optic neuritis]. / Die Neuritis nervi optici.

The diagnosis of optic neuritis (ON) is made clinically based on typical signs and symptoms such as reduced vision and painful eye movements. Very often, ON is part of or associated with a systemic disease, in particular, multiple sclerosis (MS). Differential diagnosis is necessary in untypical cases with bilateral involvement, unusual age at manifestation or associated systemic and/or neurological symptoms. Neurological examination and cerebral MRI are standard in ON work-up. CSF analysis together with MRI scans allows MS risk assessment in ON patients. Further work-up is necessary in suspected systemic autoimmune disorders, sarcoidosis or infectious causes of ON such as borreliosis.

[Process management in surgery]. / Prozessmanagement in der Chirurgie.

Process management is defined as the concept of identifying processes in a company or healthcare organization, analyzing them and improving productivity and efficiency. In hospitals, process management focuses on patient safety, an increase in economic resources and employee satisfaction. The integration of process management into clinical pathways helps to accelerate workflows and to improve the quality of patient service. The different types of process management encompass the radical concept of process renewal (revolutionary renewal) as well as the concept of evolutionary optimization. Process management in surgery is applied to preoperative, perioperative and postoperative procedures. The development and implementation of evidence-based treatment pathways can help to standardize and structure treatment processes in a surgical department. In this context, the operating room (OR) plays a particularly central role as the most important part of the healthcare provision of perioperative services. Process management is indispensable for the utilization of an optimal OR capacity taking a maximum patient safety and the desired optimal satisfaction of employees into account. The benefits of process management in the OR area are illustrated in an exemplary case study, demonstrating how innovative process management results in an increase of the operation capacity with a simultaneous reduction in costs.

Perioperative Blood Management of Preoperative Anemia Determines Long-Term Outcome in Patients with Pancreatic Surgery.

BACKGROUND/PURPOSE: Anemia affects the postoperative course of patients undergoing a major surgical procedure. However, it remains unclear whether anemia has a different impact on the long-term outcome of patients with malignant or benign pancreatic disease. METHODS: A retrospective analysis of patients undergoing pancreatic surgery for pancreatic malignancies or chronic pancreatitis was conducted between January 2012 and June 2018 at the University Hospital Dresden, Germany. The occurrence of preoperative anemia and the administration of pre-, intra-, and postoperative blood transfusions were correlated with postoperative complications and survival data by uni- and multivariate analysis. RESULTS: A total of 682 patients were included with 482 (70.7%) undergoing surgical procedures for pancreatic malignancies. Univariate regression analysis confirmed preoperative anemia as a risk factor for postoperative complications > grade 2 according to the Clavien-Dindo classification. Multivariate regression analyses indicated postoperative blood transfusion as an independent risk factor for postoperative complications in patients with a benign (OR 20.5; p value < 0.001) and a malignant pancreatic lesion (OR 4.7; p value < 0.01). Univariate and multivariate analysis revealed preoperative anemia and pre-, intra-, and postoperative blood transfusions as independent prognostic factors for shorter overall survival in benign and malignant patients (p value < 0.001-0.01). CONCLUSION: Preoperative anemia is a prevalent, independent, and adjustable factor in pancreatic surgery, which poses a significant risk for postoperative complications irrespective of the entity of the underlying disease. It should therefore be understood as an adjustable factor rather than an indicator of underlying disease severity.

[Accuracy of two autorefractors--Pediatric Autorefractor plusoptiX and Retinomax--in cycloplegic children in comparison to retinoscopy]. / Zur Messung der objektiven Refraktion in Zykloplegie im Kindesalter mit Skiaskopie und automatischer Refraktometrie mit dem Pediatric Autorefractor und dem Retinomax.

HISTORY: In children, measuring refraction is of interest particularly with regard to the risk of amblyopia. Cycloplegic retinoscopy is the gold standard method for this age group. In a prospective study we compared readings from two hand-held photorefractors, the Pediatric Autorefractor and the Retinomax, to those from retinoscopy. PATIENTS AND METHODS: 74 patients were recruited consecutively at the outpatient department of Heidelberg University Eye Hospital's Section for Strabismology and Neuroophthalmology. All patients underwent standardised cycloplegia measurements first by the Pediatric Autorefractor plusoptiX A 08 in 1 metre working distance, then adding an infrared filter to reduce interferences, followed by the Retinomax K-plus 3 in 5 cm working distance and retinoscopy as reference on the right eye. RESULTS: Spherical equivalents measured by the Pediatric Autorefractor plusoptiX A 08 coincided in 51.2% with retinoscopy (± 0.5 D). Adding an infrared filter increased this to 60.0%. However, the success rate of measurement decreased to 47% on adding an infrared filter as compared to 55.4% in cycloplegia alone. Children showed no cooperation in 11% and 16% with the infrared filter, respectively. The remaining children were not measurable by means of the device. With regard to spherical equivalents, the measurements done with Retinomax K-plus 3 coincide in 57% with those done in retinoscopy. The success rate of measurements with the Retinomax was 91%. The remaining children showed no cooperation. CONCLUSION: Retinoscopy in cycloplegia is still the method of choice when determining refraction in children. Autorefractors quickly provide results for comparison which coincide with retinoscopy in 50-60% in spherical equivalent and in 80-90% in cylindrical values. The Pediatric Autorefractor is not suited for everyday clinical routine due to a low success rate of 50% and tight measuring range of + 5.0 to -7.0 D in spherical equivalents.

Novel dual HIV maintenance therapy with nevirapine plus lamivudine retain viral suppression through 144 weeks-A proof-of-concept study.

OBJECTIVES: The aim of this proof-of-concept study is to test feasibility and efficacy of NVP plus Lamivudine (3TC) as novel simplified HIV maintenance dual therapy (DT) strategy. METHODS: Patients under combined antiretroviral treatment (cART) with fully suppressed HIV plasma viral load (pVL) >24 months-whereof >6 months on an NVP- containing regimen-were switched to oral NVP plus 3TC for 24 weeks. Patients could then decide whether to continue DT or return to the previous cART. HIV pVL was monitored monthly until week 144. The primary outcome was confirmed viral failure (RNA >100 copies/ml). Low-level detection of HIV-RNA in plasma was compared in each patient with pre-study viral load measurements. RESULTS: Twenty patients were included, switched to DT and all completed week 24. One patient decided thereafter to discontinue study participation for personal reasons. After a total of 144 observation weeks, none of the patients failed. The frequency of low- level HIV-RNA detection was not different from the period before randomization. CONCLUSIONS: Our findings are surprising but given the nature of a proof-of-concept study, the results do not support the use of this dual regimen. However, as this dual HIV maintenance strategy was feasible and effective, over a period of 144 weeks, we suggest NVP plus 3TC warrants further evaluation as potential maintenance option in patients tolerating nevirapine. A properly sized multicentre non-inferiority trial is ongoing to further evaluate the value of this DT maintenance strategy.

Increased expression of ALCAM/CD166 in pancreatic cancer is an independent prognostic marker for poor survival and early tumour relapse.

BACKGROUND: ALCAM (activated leucocyte cell adhesion molecule, synonym CD166) is a cell adhesion molecule, which belongs to the Ig superfamily. Disruption of the ALCAM-mediated adhesiveness by proteolytic sheddases such as ADAM17 has been suggested to have a relevant impact on tumour invasion. Although the expression of ALCAM is a valuable prognostic and predictive marker in several types of epithelial tumours, its role as a prognostic marker in pancreatic cancer has not yet been reported. METHODS: In this study, paraffin-embedded samples of 97 patients with pancreatic cancer undergoing potentially curative resection were immunostained against ALCAM, ADAM17 and CK19. Expression of ALCAM and ADAM17 was semiquantitatively evaluated and correlated to clinical and histopathological parameters. RESULTS: We could show that in normal pancreatic tissue, ALCAM is predominantly expressed at the cellular membrane, whereas in pancreatic tumour cells, it is mainly localised in the cytoplasm. In addition, univariate and multivariate analyses show that increased expression of ALCAM is an adverse prognostic factor for recurrence-free and overall survival. Overexpression of ADAM17 in pancreatic cancer, however, failed to be a significant prognostic marker and was not coexpressed with ALCAM. CONCLUSIONS: Our findings support the hypothesis that the disruption of ALCAM-mediated adhesiveness is a relevant step in pancreatic cancer progression. Moreover, ALCAM overexpression is a relevant independent prognostic marker for poor survival and early tumour relapse in pancreatic cancer.

Invasion front-specific overexpression of tissue inhibitor of metalloproteinase-1 in liver metastases from colorectal cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), have been implicated in invasion and metastasis. The distribution of MMPs and TIMPs in the invasion front of liver metastases from colorectal cancer were investigated in order to understand their potential role in invasiveness. MATERIALS AND METHODS: Freshly frozen material of colorectal metastases of the liver was microdissected into four separate compartments, namely pure liver, liver invasion, tumour invasion and pure tumour. RNA was isolated and analyzed on Affymetrix microarrays. Expression of TIMP-1 was confirmed by quantitative polymerase chain reaction in 10 colorectal liver metastases. Cellular localisation of TIMP-1 was examined by immunohistochemistry. RESULTS: Affymetrix microarray data revealed that several MMP and TIMP genes including MMP-2, -3, -7, -9, -11, -12, -14, -15, -16, -19 and -24, and TIMP-1, -2 and -3 were generally up-regulated in both invasion front compartments. Among these genes, TIMP-1 showed the highest expression. The qPCR results indicated an average 15-fold upregulation of TIMP-1 in the liver invasive front and an average 13-fold up-regulation in the tumor invasive front, each compared to normal liver tissue. Immunohistochemistry revealed expression of TIMP-1 in tumour epithelia as well as in host tissue cells, including fibroblastic cells. CONCLUSION: Our data indicate that tumour invasion in colorectal liver metastasis is associated with increased TIMP-1 RNA and protein levels in both tumour and host cells.