Trends in Diagnosis and Surgical Management of Patients with Perforated Peptic Ulcer

Introduction While the laparoscopic treatment of perforated peptic ulcers (PPU) has been shown to be feasible and safe, its implementation into routine clinical practice has been slow. Only a few studies have evaluated its overall utility. The aim of this study was to investigate changes in surgical management of PPU and associated outcomes. Material and Methods The study was a retrospective, single institution, population-based review of all patients undergoing surgery for PPU between 2003 and 2009. Patient demographics, diagnostic evaluation, management, and outcomes were evaluated. Results Included were 114 patients with a median age of 67 years (range, 20–100). Women comprised 59% and were older (p<0.001), had more comorbidities (p=0.002), and had a higher Boey risk score (p=0.036) compared to men. Perforation location was gastric/pyloric in 72% and duodenal in 28% of patients. Pneumoperitoneum was diagnosed by plain abdominal x-ray in 30 of 41 patients (75%) and by abdominal computerized tomography (CT) in 76 of 77 patients (98%; p<0.001). Laparoscopic treatment was initiated in 48 patients (42%) and completed in 36 patients (75% of attempted cases). Laparoscopic treatment rate increased from 7% to 46% during the study period (p=0.02). Median operation time was shorter in patients treated via laparotomy (70 min) compared to laparoscopy (82 min) and those converted from laparoscopy to laparotomy (105 min; p=0.017). Postoperative complications occurred in 56 patients (49%). Overall 30-day postoperative mortality was 16%. No statistically significant differences were found in morbidity and mortality between open versus laparoscopic repair. Conclusion This study demonstrates an increased use of CT as the primary diagnostic tool for PPU and of laparoscopic repair in its surgical treatment. These changes in management are not associated with altered outcomes

Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study

<p>Abstract</p> <p>Background</p> <p>Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.</p> <p>Methods</p> <p>Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume</p> <p>Results</p> <p>100 measurements in 50 patients (33 m/17 w; age 56 years (± 8); Child-Pugh-score 12 (± 2), serum creatinine 256 μmol (± 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m²(± 138) despite CVP within the normal range (11 mmHg (± 5). After infusion, GEDVI, CI and CVP increased (682 ml/m²(± 128) vs. 744 ml/m²(± 171), p < 0.001; 4.3 L/min/m²(± 1.1) vs. 4.7 L/min/m²(± 1.1), p < 0.001; 12 mmHg (± 6) vs. 14 mmHg (± 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm⁵/m²(± 1144) vs. 1490 dyn s/cm⁵/m²(± 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r²= 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.</p> <p>Conclusion</p> <p>In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.</p

Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males

Purpose: High-load resistance exercise contributes to maintenance of muscle mass, muscle protein quality, and contractile function by stimulation of muscle protein synthesis (MPS), hypertrophy, and strength gains. However, high loading may not be feasible in several clinical populations. Low-load blood flow restricted resistance exercise (BFRRE) may provide an alternative approach. However, the long-term protein synthetic response to BFRRE is unknown and the myocellular adaptations to prolonged BFRRE are not well described.Methods: To investigate this, 34 healthy young subjects were randomized to 6 weeks of low-load BFRRE, HLRE, or non-exercise control (CON). Deuterium oxide (D2O) was orally administered throughout the intervention period. Muscle biopsies from m. vastus lateralis were collected before and after the 6-week intervention period to assess long-term myofibrillar MPS and RNA synthesis as well as muscle fiber-type-specific cross-sectional area (CSA), satellite cell content, and myonuclei content. Muscle biopsies were also collected in the immediate hours following single-bout exercise to assess signaling for muscle protein degradation. Isometric and dynamic quadriceps muscle strength was evaluated before and after the intervention.Results: Myofibrillar MPS was higher in BFRRE (1.34%/day, p &lt; 0.01) and HLRE (1.12%/day, p &lt; 0.05) compared to CON (0.96%/day) with no significant differences between exercise groups. Muscle RNA synthesis was higher in BFRRE (0.65%/day, p &lt; 0.001) and HLRE (0.55%/day, p &lt; 0.01) compared to CON (0.38%/day) and both training groups increased RNA content, indicating ribosomal biogenesis in response to exercise. BFRRE and HLRE both activated muscle degradation signaling. Muscle strength increased 6–10% in BFRRE (p &lt; 0.05) and 13–23% in HLRE (p &lt; 0.01). Dynamic muscle strength increased to a greater extent in HLRE (p &lt; 0.05). No changes in type I and type II muscle fiber-type-specific CSA, satellite cell content, or myonuclei content were observed.Conclusions: These results demonstrate that BFRRE increases long-term muscle protein turnover, ribosomal biogenesis, and muscle strength to a similar degree as HLRE. These findings emphasize the potential application of low-load BFRRE to stimulate muscle protein turnover and increase muscle function in clinical populations where high loading is untenable

Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants’ PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges

Both male and female identity influence variation in male signalling effort

<p>Abstract</p> <p>Background</p> <p>Male sexual displays play an important role in sexual selection by affecting reproductive success. However, for such displays to be useful for female mate choice, courtship should vary more among than within individual males. In this regard, a potentially important source of within male variation is adjustment of male courtship effort in response to female traits. Accordingly, we set out to dissect sources of variation in male courtship effort in a fish, the desert goby (<it>Chlamydogobius eremius</it>). We did so by designing an experiment that allowed simultaneous estimation of within and between male variation in courtship, while also assessing the importance of the males and females as sources of courtship variation.</p> <p>Results</p> <p>Although males adjusted their courtship depending on the identity of the female (a potentially important source of within-male variation), among-male differences were considerably greater. In addition, male courtship effort towards a pair of females was highly repeatable over a short time frame.</p> <p>Conclusion</p> <p>Despite the plasticity in male courtship effort, courtship displays had the potential to reliably convey information about the male to mate-searching females. Our experiment therefore underscores the importance of addressing the different sources contributing to variation in the expression of sexually-selected traits.</p

A new tool to assess Clinical Diversity In Meta‐analyses (CDIM) of interventions

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions.STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups.RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters.CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.</p

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path