A one-to-one telestroke network: the first Italian study of a web-based telemedicine system for thrombolysis delivery and patient monitoring

Over 10 years after European approval, thrombolysis is still limited by a restricted time window and non-optimal territorial coverage. Implementation of telestroke can give a growing number of patients access to treatment. We hereby present the first Italian telemedicine study applied to both the acute and the monitoring phase of stroke care. From January 2011 to December 2013, we tested a web-based, drip, and treat interaction model, connecting the cerebrovascular specialist of one hub center to the Emergency Department of a Spoke center. We then compared thrombolysis delivered using the telestroke model with thrombolysis provided at the Hub Stroke Unit at the time when the telemedicine program was activated. Telethrombolysis data were then compared with data from the two main international telestroke projects (TEMPiS and REACH), and other European telestroke studies performed at the time of writing. We collected a total of 131 thrombolysis procedures (25 telethrombolysis and 106 thrombolysis patients at the Stroke Unit). Statistical analysis with the t test yielded no statistically significant differences between the two populations in door-to-scan, door-to-needle (DTN), and onset-to-treatment times (OTT). Our OTT and DTN pathway times were longer than the TEMPiS and REACH studies but comparable with other European telemedicine trials, despite different models of interaction and number of centers. Our study in a northeastern province of Italy confirms the potential of applying telemedicine to a cerebrovascular pathology.     

Is three-dimensional computed tomography reconstruction justified before endovascular aortic aneurysm repair?

OBJECTIVES: The endovascular management of abdominal aortic aneurysm (AAA) relies on accurate preoperative imaging for proper patient selection and operative planning. Three-dimensional (3-D) computed tomography (CT) with reformatted images perpendicular to blood flow has gained popularity as a method of AAA assessment and image-based planning before endovascular aneurysm repair (EVAR). The current study was undertaken to determine the interobserver agreement of AAA measurements obtained with axial CT and reformatted 3-D CT and to compare the consistency of the 2 methods in selecting patients for EVAR. METHODS: Eight observers assessed the axial CT and reformatted 3-D CT scans for 5 patients with AAAs to determine whether the patients were candidates for EVAR. 3-D CT with multiplanar reformatted images was performed by Medical Media Systems (MMS). Each observer measured the length and diameter of the proximal neck, maximal AAA, aortic bifurcation, common iliac diameter, and aortic angulation. The proximal neck and common iliac arteries were also assessed for thrombus, calcification, and tortuosity. Agreement of the measurements on axial CT scans was compared with those on MMS CT scans by calculating the kappa statistic. Complete agreement was defined as kappa = 1.0. The limits of agreement between observers were also calculated. RESULTS: The cumulative interobserver agreement of MMS CT scans (kappa =.81) was greater than for axial CT scans (kappa =.59). The kappa value for each of the diameter measurements was greater with the MMS CT scans. In 79% of cases the observers' measurements were less than 2 mm from the mean with MMS CT, compared with 59% for axial CT. The kappa value for deciding whether a patient was an endograft candidate on the basis of aortic neck was greater with the MMS CT (0.92 vs 0.63). The limits of agreement between observers were also better with the MMS CT. CONCLUSIONS: The interobserver agreement in planning EVAR is significantly better with MMS CT compared with traditional axial CT. The routine use of MMS CT appears justified before EVAR to improve the accuracy and consistency of patient selection.     

Back pain and disability after lumbar laminectomy: is there a relationship to muscle retraction?

OBJECTIVE: Preliminary studies have suggested that prolonged retraction of the paraspinal muscle during spinal surgery may produce ischemic damage. We report the continuous measurement of intramuscular pressure (IMP) during decompressive lumbar laminectomy and its relationship to subsequent back pain and disability. METHODS: Twenty patients undergoing two-level decompressive lumbar laminectomy for lumbar canal stenosis were recruited. Back pain and disability were assessed by use of the Visual Analog Score (VAS), Oswestry Disability Index (ODI), and Short-Form 36 (SF-36) Health Survey. During surgery, IMP was recorded continuously from the multifidus muscle by use of a pressure transducer. The intramuscular perfusion pressure (IPP) was estimated as the difference between the patient's mean arterial pressure and IMP. RESULTS: Two muscle retractors were used: the Norfolk and Norwich (n = 10) and the McCulloch (n = 10). The mean duration of deep muscle retraction was 62.7 +/- 8 minutes (range, 19-133 min). On application of deep muscle retraction, there was a rapid and sustained increase in IMP (P < 0.001), and overall, the calculated mean IPP approached 0 mm Hg or less during this period (P < 0.001). On release of deep muscle retraction, there was a rapid decrease in IMP to preoperative levels. The IPP was greater with the Norfolk and Norwich than the McCulloch retractor (P < 0.001). Compared with preoperative values, there was a decrease in ODI (P < 0.001) and VAS for back pain (P < 0.001) at discharge and 4 to 6 weeks and 6 months after surgery. In addition, there was a decrease in SF-36 scores at 6 months compared with preoperative values (P < 0.001). Total duration of muscle retraction greater than 60 minutes was associated with worse VAS scores for back pain and ODI and SF-36 scores for disability at 6 months after surgery (P < 0.05). There was no relationship between the VAS, ODI, and SF-36 scores and other parameters measured, including the mean IPP, retractor type, operating surgeon, and wound length. CONCLUSION: The McCulloch retractor generates a higher IMP than the Norfolk and Norwich retractor. However, postoperative improvement in VAS, ODI, and SF-36 scores in these patients was associated with a shorter duration of muscle retraction and not the degree of IMP or IPP generated. In this respect, periodic relaxation of the paraspinal muscle retractors during surgery to allow muscle perfusion may help to reduce postoperative back pain and disability.     

Exome Sequence Data From Multigenerational Families Implicate AMPA Receptor Trafficking in Neurocognitive Impairment and Schizophrenia Risk

Schizophrenia is a mental disorder characterized by impairments in behavior, thought, and neurocognitive performance. We searched for susceptibility loci at a quantitative trait locus (QTL) previously reported for abstraction and mental flexibility (ABF), a cognitive function often compromised in schizophrenia patients and their unaffected relatives. Exome sequences were determined for 134 samples in 8 European American families from the original linkage study, including 25 individuals with schizophrenia or schizoaffective disorder. At chromosome 5q32–35.3, we analyzed 407 protein-altering variants for association with ABF and schizophrenia status. For replication, significant, Bonferroni-corrected findings were tested against cognitive traits in Mexican American families (n = 959), as well as interrogated for schizophrenia risk using GWAS results from the Psychiatric Genomics Consortium (PGC). From the gene SYNPO, rs6579797 (MAF = 0.032) shows significant associations with ABF (P = .015) and schizophrenia (P = .040), as well as jointly (P = .0027). In the Mexican American pedigrees, rs6579797 exhibits significant associations with IQ (P = .011), indicating more global effects on neurocognition. From the PGC results, other SYNPO variants were identified with near significant effects on schizophrenia risk, with a local linkage disequilibrium block displaying signatures of positive selection. A second missense variant within the QTL, rs17551608 (MAF = 0.19) in the gene WWC1, also displays a significant effect on schizophrenia in our exome sequences (P = .038). Remarkably, the protein products of SYNPO and WWC1 are interaction partners involved in AMPA receptor trafficking, a brain process implicated in synaptic plasticity. Our study reveals variants in these genes with significant effects on neurocognition and schizophrenia risk, identifying a potential pathogenic mechanism for schizophrenia spectrum disorders.Key words: schizophrenia, cognition, SYNPO, WWC1, synaptic plasticity     

A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney

Background

The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.

Methods

To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8?weeks.

Results

CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak ??SMA staining. Furthermore, PCR analysis demonstrated that TGF-?? and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.

Conclusion

We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.     

Salvage banding for failed Roux-en-Y gastric bypass

BackgroundAfter Roux-en-Y gastric bypass (RYGB), a substantial number of patients do not achieve successful long-term weight loss. In cases of loss of restriction, the application of an adjustable gastric band (“salvage banding”) over the gastric pouch, or gastrojejunostomy, could prevent weight regain or increase weight loss. The objective of this literature review is to provide an overview of the studies that report the effect of salvage banding after failed RYGB.MethodsA systemic literature search was conducted in PubMed, Google Scholar, Medline, the Cochrane Library, and the online websites of specific bariatric surgery journals to identify all relevant studies describing salvage banding after failed RYGB.ResultsSeven studies, with a total of 94 patients, were included for a systemic literature review. Inclusion criteria for salvage banding varied from unsuccessful weight loss to technical pouch failure. After salvage banding, all studies reported further weight loss, varying from 55.9%–94.2% excess body mass index loss (EBMIL) after 12–42 months of follow-up. In the included study group, 18% (17/94) of the patients developed long-term complications requiring a re-revision in 17% (16/94) of the cases.ConclusionThe results of all 9 studies that were included in this review report a further increase in weight loss after salvage banding for failed RYGB. In case of insufficient weight loss or technical pouch failure after RYGB, all reports suggest that salvage banding is a safe and feasible revisional procedure. Prospective studies are necessary to determine to the success of direct application of an adjustable gastric band in primary RYGB.     

Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia–reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.Recent evidence suggests that hypoglycemia may play an important role in the vascular complications of diabetes (1). Hypoglycemia causes oxidative stress (2), inflammation (3), and endothelial dysfunction (4). Oxidative stress is considered the key player in the pathogenesis of diabetes complications (5). During hyperglycemia, oxidative stress is produced at the mitochondrial level (5), similarly as in hypoglycemia (2). Therefore, oxidative stress might be considered the common factor linking hyperglycemia, hypoglycemia, and the vascular complications of diabetes. Consistent with this hypothesis is the evidence that hyperglycemia (6) and hypoglycemia both produce endothelial dysfunction and inflammation through the generation of oxidative stress (4,7). Endothelial dysfunction and inflammation are well-recognized pathogenic factors for vascular disease, particularly in diabetes (8).There is, however, evidence that free radical production rises, not only during hypoglycemia but particularly during glucose reperfusion after hypoglycemia (9). In both mice and cultured neurons, hypoglycemia, followed by different concentrations of glucose reperfusion, has been linked to a degree of superoxide production and neuronal death that increased proportionally with glucose concentrations during the reperfusion period (9).Until now, little attention has been given to studying the effects of recovery from hypoglycemia. The aim of this study was to evaluate these effects and, in particular, to determine if the level of glycemia reached during recovery could have a different impact, in vivo, on oxidative stress generation, inflammation, and endothelial function.     

Assessing the practice of data quality evaluation in a national clinical data research network through a systematic scoping review in the era of real-world data

ObjectiveTo synthesize data quality (DQ) dimensions and assessment methods of real-world data, especially electronic health records, through a systematic scoping review and to assess the practice of DQ assessment in the national Patient-centered Clinical Research Network (PCORnet).Materials and MethodsWe started with 3 widely cited DQ literature—2 reviews from Chan et al (2010) and Weiskopf et al (2013a) and 1 DQ framework from Kahn et al (2016)—and expanded our review systematically to cover relevant articles published up to February 2020. We extracted DQ dimensions and assessment methods from these studies, mapped their relationships, and organized a synthesized summarization of existing DQ dimensions and assessment methods. We reviewed the data checks employed by the PCORnet and mapped them to the synthesized DQ dimensions and methods.ResultsWe analyzed a total of 3 reviews, 20 DQ frameworks, and 226 DQ studies and extracted 14 DQ dimensions and 10 assessment methods. We found that completeness, concordance, and correctness/accuracy were commonly assessed. Element presence, validity check, and conformance were commonly used DQ assessment methods and were the main focuses of the PCORnet data checks.DiscussionDefinitions of DQ dimensions and methods were not consistent in the literature, and the DQ assessment practice was not evenly distributed (eg, usability and ease-of-use were rarely discussed). Challenges in DQ assessments, given the complex and heterogeneous nature of real-world data, exist.ConclusionThe practice of DQ assessment is still limited in scope. Future work is warranted to generate understandable, executable, and reusable DQ measures.     

Pancreatoduodenectomy for Tumors of Vater’s Ampulla: Report on 94 Consecutive Patients

Evaluation of prognostic factors of adenocarcinoma of Vater’s ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival.Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.     

Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study

Purpose

To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy.

Methods

A group of 29 patients underwent an evaluation of myocardial perfusion with ^99mTc-tetrofosmin CZT scintigraphy and adrenergic innervation with ¹²³I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed ¹²³I-MIBG defect score (SS-MIBG), were determined. Regional tracer uptake for both ^99mTc-tetrofosmin and ¹²³I-MIBG was also calculated. Finally, the presence of significant myocardial mechanical dyssynchrony was evaluated in phase analysis on gated CZT images and the region of latest mechanical activation identified.

Results

Significant mechanical dyssynchrony was present in 17 patients (59 %) and associated with higher SRS (P?=?0.030), SMS (P?<?0.001), STS (P?=?0.003) and early SS-MIBG (P?=?0.037) as well as greater impairments in left ventricular ejection fraction (P?<?0.001) and end-diastolic volume (P?<?0.001). In multivariate analysis a higher end-diastolic volume remained the only predictor of mechanical dyssynchrony (P?=?0.047). Interestingly, while in the whole population regional myocardial perfusion and adrenergic activity were strongly correlated (R?=?0.68), in patients with mechanical dyssynchrony the region of latest mechanical activation was predicted only by greater impairment in regional ¹²³I-MIBG uptake (P?=?0.012) that overwhelmed the effect of depressed regional perfusion.

Conclusion

Left ventricular mechanical dyssynchrony is associated with greater depression in contractile function and greater impairments in regional myocardial perfusion and sympathetic activity. In patients with dyssynchrony, the region of latest mechanical activation is characterized by a significantly altered adrenergic tone.