Locally advanced mid/low rectal cancer with synchronous resectable liver metastases: systematic review of the available strategies and outcome.

The management of patients with locally advanced mid/low rectal cancer with resectable liver metastases is complex because of the need to combine the optimal treatment of both tumors. This study aims to review the available treatment strategies and compare their outcome, focusing on radiotherapy (RT) and liver-first approach (LFA). A systematic review was performed in PubMed, Embase, and web sources including articles published between 2000 and 02/2023 and reporting mid-/long-term outcomes. Overall, twenty studies were included (n = 1837 patients). Three- and 5-year overall survival (OS) rates were 51-88% and 36-59%. Although several strategies were reported, most patients received RT (1448/1837, 79%; > 85% neoadjuvant). RT reduced the pelvic recurrence risk (5.8 vs. 13.5%, P = 0.005) but did not impact OS. Six studies analyzed LFA (n = 307 patients). LFA had a completion rate similar to the rectum-first approach (RFA, 81% vs. 79%) but the interval strategy-an LFA variant with liver surgery in the interval between radiotherapy and rectal surgery-had a better completion rate than standard LFA (liver surgery/radiotherapy/rectal surgery, 92% vs. 75%, P = 0.011) and RFA (79%, P = 0.048). Across all series, LFA achieved the best survival rates, and in one paper it led to a survival advantage in patients with multiple metastases. In conclusion, different strategies can be adopted, but RT should be included to decrease the pelvic recurrence risk. LFA should be considered, especially in patients with high hepatic tumor burden, and RT before liver surgery (interval strategy) could maximize its completion rate.

Molecular architecture of the ciliary tip revealed by cryo-electron tomography.

Cilia are essential organelles that protrude from the cell body. Cilia are made of a microtubule-based structure called the axoneme. In most types of cilia, the ciliary tip is distinct from the rest of the cilium. Here, we used cryo-electron tomography and subtomogram averaging to obtain the structure of the ciliary tip of the ciliate Tetrahymena thermophila. We show the microtubules in the tip are highly cross-linked with each other and stabilised by luminal proteins, plugs and cap proteins at the plus ends. In the tip region, the central pair lacks the typical projections and twists significantly. By analysing cells lacking a ciliary tip-enriched protein CEP104/FAP256 by cryo-electron tomography and proteomics, we discovered candidates for the central pair cap complex and explain potential functions of CEP104/FAP256. These data provide new insights into the function of the ciliary tip and inform about the mechanisms of ciliary assembly and length regulation.

Genetic fingerprinting of salmon louse (Lepeophtheirus salmonis) populations in the North-East Atlantic using a random forest classification approach.

Caligid sea lice represent a significant threat to salmonid aquaculture worldwide. Population genetic analyses have consistently shown minimal population genetic structure in North Atlantic Lepeophtheirus salmonis, frustrating efforts to track louse populations and improve targeted control measures. The aim of this study was to test the power of reduced representation library sequencing (IIb-RAD sequencing) coupled with random forest machine learning algorithms to define markers for fine-scale discrimination of louse populations. We identified 1286 robustly supported SNPs among four L. salmonis populations from Ireland, Scotland and Northern Norway. Only weak global structure was observed based on the full SNP dataset. The application of a random forest machine-learning algorithm identified 98 discriminatory SNPs that dramatically improved population assignment, increased global genetic structure and resulted in significant genetic population differentiation. A large proportion of SNPs found to be under directional selection were also identified to be highly discriminatory. Our data suggest that it is possible to discriminate between nearby L. salmonis populations given suitable marker selection approaches, and that such differences might have an adaptive basis. We discuss these data in light of sea lice adaption to anthropogenic and environmental pressures as well as novel approaches to track and predict sea louse dispersal.

Multi-screen electronic alerts to augment venous thromboembolism prophylaxis.

Venous thromboembolism (VTE) prophylaxis in high-risk patients is frequently underutilised. We previously devised a one-screen computer alert program that identified hospitalised patients at high risk for VTE who were not receiving prophylaxis and advised their physicians to prescribe prophylaxis. While this strategy reduced the 90-day incidence of symptomatic VTE by 41%, the majority of electronic alerts were ignored. We have now developed a serial three-screen alert computer program designed to educate physicians who initially declined to order prophylaxis after a single screen alert. Of a total cohort of 880, the responsible physicians for 425 patients received a single electronic alert, whereas 455 who declined prophylaxis after the first screen received the second and third screens of the novel three-screen alert. Our enhanced serial three-screen alert program generated VTE prophylaxis orders for 58.4% of the 455 patients whose physicians initially declined to order prophylaxis following the one-screen alert. There was no significant difference in symptomatic 90-day VTE rates between the two cohorts (2.8% for the one-screen vs. 2.2% for the three-screen, p=0.55). We conclude that our three-screen computer alert program can markedly increase prophylaxis among physicians who decline an initial single screen alert.

Evaluation of an automated extraction system in combination with Affigene CMV Trender for CMV DNA quantitative determination: comparison with nested PCR and pp65 antigen test.

CMV viral load quantitation is a powerful tool to assist clinicians in making accurate diagnoses, managing post-transplant CMV disease and monitoring antiviral therapy. The aim of this study was to evaluate the performance of Affigene CMV Trender for CMV viral load determination used in combination with a non-dedicated nucleic acid extraction system (BioRobot MDx) for high-throughput routine. Linearity, reproducibility and sensitivity were examined. Clinical samples were used to compare results obtained with the Affigene CMV Trender, with an "in house" nested PCR used for routine diagnosis and with pp65 antigenemia. The results indicated that the test is linear in the range of 1.81-5.18 Logcopies/ml and that sensitivity is 77 copies/ml. The concordance of the Affigene CMV Trender with nested PCR was high, (k=0.91, IC 95%=0.82-1.00), whereas a substantial concordance with pp65 antigenemia was observed (k=0.64, IC 95%=0.54-0.73). In conclusion, combined use of a non-dedicated automated nucleic acid extraction method with the Affigene CMV Trender results in an accurate high throughput system, suitable for routine laboratory monitoring of CMV infection.

Improving allergy alerting in a computerized physician order entry system.

Computerized physician order entry has been shown to reduce the frequency of serious medication errors. Decision support tools such as alerting functions for patient medication allergy are a key part of these applications. However, optimal performance requires iterative refinement. As systems become increasingly complex, mechanisms to monitor their performance become increasingly critical. We analyzed trend data obtained over a five-year period that showed decreasing compliance to allergy alert functions within computerized order entry. Many medication-allergy pairs were being consistently overridden. Renewal policies affecting reordering narcotics also contributed heavily to this trend. Each factor revealed a system-wide trend that could result in suggestions for policy or software change. Monitoring trends such as these is very important to maintain software correctness and ensure user trust in alerting systems, so users remain responsive to computerized alerts.

P-CAPE: a high-level tool for entering and processing clinical practice guidelines. Partners Computerized Algorithm and Editor.

The Partners Computerized Algorithm Processor and Editor (P-CAPE) is a high-level tool intended to remove the programming bottleneck for implementing practice guidelines in our computer-based record system, and to integrate guideline-based advice into the clinician's workflow. P-CAPE has three major components: 1) An Editor that allows an analyst to enter the parameters of a guideline in the form of an algorithm; 2) A Navigator that processes the steps of the guideline and logs all transactions in a patient-specific file; and 3) A clinician Notifier that sends messages to a patient's covering clinician, seeking data or presenting recommendations and order sets that can be processed by the system. P-CAPE's guideline object model was adapted from the InterMed Collaboratory GuideLine Interface Format (GLIF).

Effect of cuspid positioning in the cleft at the time of secondary alveolar bone grafting on eventual graft success.

This investigation was to determine the relationship between the success of secondary alveolar bone grafting and the position of the permanent cuspid relative to the cleft at the time of grafting. In this retrospective study utilizing periapical radiographs take on cleft patients to evaluate bone grafting results, the subjects were patients treated at the Lancaster Cleft Palate Clinic, a private institution specializing in the care of cleft patients. Sixty-seven patients (20 BCLP; 47 UCLP) were selected for this study based on availability of quality radiographs and a minimum of 6-month post-surgical follow-up. All patients underwent alveolar bone grafting (mean age, 10 years 7 months). Presurgical radiographs were taken within 3 months of the operation. Post-surgical radiographs were taken to evaluate the outcome of grafting (mean follow-up, 2 years 10 months). Radiographs were traced and digitized on a total of 86 cleft sites. Presurgically, a ratio was used to determine the amount of cuspid crown emerged through the alveolus into the cleft site relative to the anatomic cuspid-crown length. Post-surgically, ratios of bone support for the teeth mesial and distal to the cleft were established by dividing the amount of root covered by bone by the anatomic root length. Ratios expressing the height of alveolar crest relative to the cementoenamel junction (CEJ) of adjacent teeth and amount of alveolar notching relative to the mesial tooth root length were also evaluated. Linear regressions of each of the five ratios of graft outcome on the cuspid-eruption ratio were done. No significant correlations could be found between final graft success and the amount of cuspid crown exposed in the cleft at the time of grafting. Cuspid position could not be shown to be a significant factor in determining graft success.

Characterization of sulfation patterns of beef and pig mucosal heparins by nuclear magnetic resonance spectroscopy.

Though differing only slightly in their degrees of sulfation, heparin preparations from pig mucosa and those from beef mucosa have consistently different 13C- and 1H-NMR spectra, which provide useful fingerprints for distinguishing the two types of heparin. Integrated areas of NMR signals associated with minor, undersulfated sequences (assigned by comparison with mono-dimensional spectra of selectively desulfated heparins and by analysis of two-dimensional spectra of heparins prepared from pig and beef mucosa) permit quantitation of differences in sulfation patterns. Undersulfation of pig mucosal heparins at position 6 of the hexosamine units, determined by 13C-NMR and expressed as percent glucosamines nonsulfated at C6 referred to total glucosamines, is substantially lower for pig mucosal heparins than for beef mucosal heparins (16.9-21.7% vs 36.7-40.7%; average values: 18.6% vs 40.3%). By contrast, undersulfation at position 2 of the iduronic acid units, determined by 1H-NMR and expressed as percent nonsulfated iduronic acid referred to total (sulfated + nonsulfated) iduronic acid is significantly higher for pig mucosal preparations (9.6-13.5% vs 2.1-2.7%; average values: 12.7% vs 2.3%). Pig mucosal heparins also have a significantly higher content of 3-O-sulfated glucosamine units, which are markers for the active site of heparin for antithrombin-III.

Detecting alerts, notifying the physician, and offering action items: a comprehensive alerting system.

We developed and evaluated a system to automatically identify serious clinical conditions in inpatients. The system notifies the patient's covering physician via his pager that an alert is present and offers potential therapies for the patient's condition (action items) at the time he views the alert information. Over a 6 month period, physicians responded to 1214 (70.2%) of 1730 alerts for which they were paged; they responded to 1002 (82.5% of the 1214) in less than 15 minutes. They said they would take action in 71.5% of the alerts, and they placed an order directly from the alert display screen in 39.4%. Further study is needed to determine if this alerting system improves processes or outcomes of care.

Relationship of knee extensor strength and hopping test performance in the assessment of lower extremity function.

Traditionally, open kinetic chain rehabilitation and evaluation have been used as the primary tool to assess a patient's strength and readiness to progress to a higher functional level. More recently, closed kinetic chain activities have been developed and well documented as an alternate means to prepare and evaluate a patient's ability to return to a higher functional level. However, a dearth in recent literature comparing the correlation between an open kinetic chain isokinetic strength test and performance on a functional performance test exists. Therefore, the purpose of this study was to examine the relationship between a knee extensor strength and functional performance test, specifically the one-legged hop for distance. Twenty subjects (mean = 20.7 years), with no prior history of lower extremity injury, participated in the study consisting of isokinetic evaluation of the quadriceps muscle using a Kinetic Communicator and a one-legged hop for distance. Isokinetic testing was performed at 240 degrees/sec. All tests were performed on the dominant and nondominant limbs. Pearson product moment correlation coefficients for peak torque and distance hopped were .78 for the dominant leg and .65 for the nondominant leg (p < .05). These results support the belief that isokinetic strength does not correlate strongly with functional tasks.

[Possibility of presymptomatic diagnosis of familial polyposis coli]. / Possibilità di diagnosi presintomatica nella poliposi familiare del colon.

Familial polyposis coli (FPC) is an autosomal dominant inherited disease characterized by an incidence of 1:7000-23000 born alive and by an onset of colorectal cancer in all untreated patients. This diagnosis is obtained mostly in presence of symptoms and in a low percentage after a screening, so it would be very important to have a clinical, biochemical or genetic marker to identify the affected subjects before the onset of the colonic polyps. In the last years many Authors have tested the hypertrophy of retinal pigmented epithelium (CHRPE) in the FPC affected families with interesting results. The aim of our study is to evaluate the predictive role of this clinical marker. 87 subjects have been submitted to ophthalmoscopy: 17 FPC affected patients, 40 first degree relatives and 30 no-polyposis colorectal cancer affected patients. The positivity (CHRPE +) was respectively 88.2%, 45% and 0. The first relatives degree aged more than ten years old have been submitted to the rectosigmoidoscopy and 8/9 CHRPE + persons resulted affected, while all CHRPE--examined were healthy. We have analysed the characteristics of CHRPE, its incidence and sensitivity and in FPC affected patients and in their first degree relatives, with positive results. At the end the CHRPE research and in our and in other experiences presents many advantages: low cost, easy feasibility, repeatability, high sensitivity and specificity. We consider that until the advent of valid routinary genetic tests it can be a good clinical marker in FPC affected families.