Selective synthesis of boron-substituted enynes via a one-pot diboration/protodeboration sequence.

An efficient and facile one-pot protocol to access enynylboronates via a Pt-catalyzed diboration/protodeboration strategy has been developed. The reaction is suitable for various silylsubstituted symmetrical and unsymmetrical 1,3-diynes, leading to π-conjugated organoboron compounds with excellent regio- and stereoselectivity.

Polyp characteristics at screening colonoscopy and post-colonoscopy colorectal cancer mortality: a retrospective cohort study.

BACKGROUND AND AIMS: Polyp size and high-grade dysplasia in polyps at screening colonoscopy are considered risk factors for post-colonoscopy colorectal cancer (PCCRC) development and death, which might be averted by surveillance colonoscopy. However, robust evidence backing these risk factors is lacking. We aimed to investigate whether polyp size or dysplasia grade is associated with PCCRC mortality. METHODS: This was a retrospective study including individuals of the Austrian Quality Certificate for Screening Colonoscopy who underwent a colonoscopy between January 2007 and December 2020. We investigated the association of polyp size and dysplasia in polyps with PCCRC mortality according to Cox regression analysis. In addition, whether patients with certain polyp characteristics had similar risk for CRC death compared with the Austrian population was assessed by calculating standardized mortality ratios (SMRs). RESULTS: A total of 316,001 individuals were included. After a median follow-up time of 5.27 years (95% confidence interval [CI], 5.25-5.29), a significant association of polyps 10 to 20 mm (hazard ratio, 4.00; 95% CI, 2.46-6.50; P < .001) as well as high-grade dysplasia (hazard ratio, 6.61; 95% CI, 3.31-13.2; P < .001) with PCCRC death was observed. PCCRC mortality was significantly lower than the expected CRC mortality in the general population in patients with polyps <10 mm and without high-grade dysplasia (SMR, .27; 95% CI, .21-.33; P < .001), which was not observed for patients with polyps ≥10 mm or with high-grade dysplasia (SMR, 2.05; 95% CI, 1.64-2.57; P < .001). CONCLUSIONS: Polyp size ≥10 mm and high-grade dysplasia are associated with PCCRC mortality in screening patients. The data suggest that these patients might benefit most from surveillance colonoscopy.

Comparison of adenoma detection rate and proximal serrated polyp detection rate and their effect on post-colonoscopy colorectal cancer mortality in screening patients.

BACKGROUND: Patients with serrated polyps are at increased risk for post-colonoscopy colorectal cancer (PCCRC); however, evidence for a dedicated serrated polyp detection rate is lacking. The aim of this study was to investigate the association of the proximal serrated polyp detection rate (PSDR) and adenoma detection rate (ADR) with PCCRC death. METHODS: This was a retrospective analysis within the Austrian quality assurance program for screening colonoscopy. Spearman's rank coefficient was calculated for the assessment of association between ADR and PSDR. Whether ADR or PSDR were associated with colorectal cancer mortality was assessed by Cox proportional hazards model. RESULTS: 229/729 screening colonoscopies performed by 308 endoscopists were analyzed. The ADR (hazard ratio [HR] per 1 percentage point increase 0.98, 95 %CI 0.96-0.99) as well as the PSDR (HR per 1 percentage point increase 0.97, 95 %CI 0.94-0.99) were significantly associated with PCCRC death. The correlation coefficient of the ADR and PSDR calculated at every colonoscopy was 0.70 (95 %CI 0.70-0.71), and the corresponding PSDR value for an ADR performance standard of 25 % was 11.1 %. At the end of the study period, 86 endoscopists (27.9 %) reached an ADR of > 25 % and a PSDR of > 11.1 %. CONCLUSIONS: The ADR as well as the PSDR were associated with PCCRC death. Striving for a high PSDR in addition to a high ADR might reduce the risk for PCCRC mortality in patients undergoing screening colonoscopy.

[Pt(PPh3)4]-Catalyzed Selective Diboration of Symmetrical and Unsymmetrical 1,3-Diynes.

A straightforward, efficient, and selective method for the preparation of novel boryl-functionalized enynes or dienes via [Pt(PPh3)4]-catalyzed diboration of a broad spectrum of symmetrical and unsymmetrical 1,3-diynes was developed. The catalytic cycle of diboration was proposed on the basis of low-temperature 31P NMR studies. An alternative isolation method via product condensation on a cold finger was developed, which, in contrast to previous literature reports, eliminates the need for the additional transformation of rapidly decomposing enynyl pinacol boronates to more stable silica-based column chromatography derivatives during the separation step. To prove the efficiency of this simple catalytic protocol, bisboryl-functionalized enynes were synthesized in a gram scale and tested as useful building blocks in advanced organic transformations, such as hydrosilylation and Suzuki and sila-Sonogashira couplings. The presence of silyl, boryl, as well as other functions like halogen or alkoxy in their structures builds a new class of multifunctionalized enynes that might be modified in various chemical reactions.

Impact of restrictions due to COVID-19 on a quality-assured screening colonoscopy program.

Background and study aims On February 25, 2020, the first patient was diagnosed with COVID-19 in Austria. On March 16, 2020, the Austrian government imposed restrictions and subsequently the Austrian Medical Association recommended minimizing screening examinations in compliance with government restrictions. The aims of this study were to evaluate the impact of this recommendation on the number of colonoscopies performed weekly and detection of non-advanced adenomas, advanced adenomas (AA) and colorectal cancer (CRC) and to calculate how many undetected adenomas could have developed into CRC. Methods We analyzed the number of colonoscopies and pathological findings within a quality assured national colorectal cancer screening program before the COVID-19 pandemic (March 1, t 2019 to September 1, 2019, Period 1) and compared those rates to months during which access to colonoscopy was limited (March 1, 2020 and September 1, 2020, Period 2) with a Wilcoxon-rank-test and a chi-square test. Results A total of 29,199 screening colonoscopies were performed during Period 1 and 24,010 during Period 2. The mean rate of colonoscopies per week during Period 1 was significantly higher than during Period 2 (808,35 [SD = 163,75] versus 594,50 [SD = 282,24], P  = 0.005). A total of 4,498 non-advanced adenomas were detected during Period 1 versus 3,562 during Period 2 ( P  < 0.001). In total 1,317 AAs and 140 CRCs were detected during Period 1 versus 919 AAs and 106 CRCs during Period 2. These rates did not differ significantly ( P  = 0.2 and P  = 0.9). Conclusions During the COVID-19 crisis, the number of colonoscopies performed per week was significantly lower compared to the year before, but there was no difference in the detection of CRCs and AAs.

'I hear and I forget. I see and I remember. I do and I understand.'- incorporating high-fidelity medical simulation into the undergraduate nephrology course.

BACKGROUND: Medical simulation is a teaching method, which enables the development of clinical skills by implementing a simulation scenario in a true-to-life environment, but without exposing patients to any risk. So far, there has been no information on the use of high-fidelity simulation in undergraduate clinical nephrology teaching. Aim of this study was to analyze students' opinions and reactions to the simulation module in nephrology. METHODS: The survey consisting of the Satisfaction with Simulation Experience Scale (SSES) and open-ended question concerning the overall impression of classes was conducted among 103 5th year medical students, who took part in the simulation training in nephrology. SSES consisted of three parts (debriefing, reasoning, education). Statements from the open-ended question were interpreted by means of the Atlas.ti software for qualitative data analysis. RESULTS: The overall score for simulation classes was 4.39 ± 0.69 points. Students rated debriefing, reasoning and education at 4.43 ± 0.78, 4.32 ± 0.7 and 4.39 ± 0.73 points, respectively. 87.4% and 84.5% of participants agreed that simulation developed their 'clinical reasoning' and 'decision-making' skills in nephrology, respectively. Thematic analysis revealed that students evaluated the module as 'interesting', 'useful' and 'informative', but they found number of classes significantly insufficient. Students pointed out that due to the small emphasis placed on practical aspects in the existing curriculum e.g. routes of drug administration and conversion of doses, they could not fully benefit from simulation. CONCLUSION: Medical simulation is a valuable constituent of the nephrology course. Putting greater emphasis on practical aspects from the beginning of training may enable students to benefit more from simulation modules.

Impact of adenoma detection rate on detection of advanced adenomas and endoscopic adverse events in a study of over 200,000 screening colonoscopies.

BACKGROUND AND AIMS: Adenoma detection rate (ADR) is the best established quality parameter for screening colonoscopy. Guidelines recommend a target ADR >25% because previous studies have shown that patients of endoscopists with higher ADRs have a lower risk of postcolonoscopy interval cancers. However, studies have shown that improvement in ADR mainly results in increased detection of clinically irrelevant nonadvanced adenomas (NAAs). The impact of ADR on the detection of advanced adenomas (AAs) as well as adverse event rates has yet to be determined. METHODS: A total of 218,193 screening colonoscopies performed between 2007 and 2010 by 262 endoscopists within the Austrian quality assurance program were analyzed. We divided endoscopists into quintiles based on ADRs and calculated mean advanced ADRs (AADRs), NAA detection rates (NAADRs), and adverse event rates for each quintile. Spearman rank-order was used to calculate overall correlations between ADRs and AADRs as well as adverse event rates. Endoscopists with an ADR <25% were compared with those with an ADR >25%. RESULTS: Fifty-one percent of patients were women. Mean ADR was 23.03% (95% confidence interval [CI], 21.93-24.13), AADRs 7.72% (95% CI, 7.19-8.25), and NAADRs 15.31% (95% CI, 14.36-16.27). Overall, there was a significant correlation between ADR and AADR (rho = .51; P < .001). When ADR was divided into quintiles, mean AADR increased with increasing ADR. Even in the highest ADR group (ADR, 31.36%-52.27%) there was a further increase in AADR with a mean of 10.75% (95% CI, 9.31-12.19). Importantly, NAADRs increased continuously with improvement in ADRs but never dissociated from a simultaneous improvement in AADRs. However, there was also a significant correlation of ADRs and endoscopic adverse events (rho = .26, P < .001), even if the perforation rate of .028% (95% CI, .004-.052) in the highest ADR group still remained within the accepted limits based on guidelines. CONCLUSIONS: Increasing ADR is associated with improved detection of AAs and therefore is likely to prevent more cases of colorectal cancer. However, higher ADR was also associated with a higher rate of adverse events, although the adverse event rate was low.

Resection rates and safety profile of cold vs. hot snare polypectomy in polyps sized 5-10 mm and 11-20 mm.

BACKGROUND AND AIMS: Hot snare (HS) is widely used for the resection of adenomas >5 mm. The cold snare (CS) has a better safety profile and is more cost-effective. The aims of this study were to evaluate effectiveness and safety of CS polypectomy (CSP) compared to HS polypectomy (HSP) for adenomas sized 5-10 mm and 11-20 mm. METHODS: 4018 colonoscopies performed within "quality certificate for screening colonoscopy" with one polypectomy of an adenoma sized 5-20 mm each were included. Retrieval rates, complete resection rates and complication rates were assessed and compared between CSP and HSP for adenomas sized 5-10 mm and 11-20 mm. Histologic subgroups were additionally assessed. RESULTS: Complete resection rates (5-10 mm: CSP: 89.4% vs. HSP: 87.9%, p = 0.33; 11-20 mm: CSP: 81.8% vs. 80.9%; p = 1), retrieval rates (5-10 mm: CSP: 99.5% vs. HSP: 99.4%, p = 0.76; 11-20 mm: CSP: 100% vs. HSP: 99%, p = 1) and complication rates (5-10 mm: CSP: 0.2% vs. HSP: 0.2%; p = 1; 11-20 mm: CSP: 0% vs. HSP: 1%, p = 1) were equal between CSP and HSP for adenomas sized 5-10 mm as well as 11-20 mm. For serrated adenomas sized 5-10 mm, HSP was superior to CSP (88.7% vs. 77.2%, p < 0.05) regarding the complete resection rate, but not for advanced adenomas (HSP: 89.1% vs. 87.3%, p = 0.69) or adenomas with high-grade dysplasia (HSP: 76.7% vs. 75%, p = 1). CONCLUSION: This study further supports the use of CSP for polyps sized 5-10 mm and additionally suggests also using CSP for polyps sized 11-20 mm. These findings, as well as the best method for resection of serrated polyps should be validated in further studies.

Evaluation of adenomas per colonoscopy and adenomas per positive participant as new quality parameters in screening colonoscopy.

BACKGROUND AND AIMS: The primary aim of this study was to evaluate adenomas per positive participant (APP) and adenomas per colonoscopy (APC) as new quality parameters in screening colonoscopy. Furthermore, we wanted to assess whether these parameters differ depending on the setting or profession. METHODS: Colonoscopy records were obtained from the database of the Austrian certificate of quality for screening colonoscopy. The Spearman correlation was calculated to compare the adenoma detection rate (ADR), APC, APP, and advanced ADR. The parameters were compared between surgeons and internists and between private practices and hospitals by using the t test. RESULTS: A total of 44,142 colonoscopies performed by 202 endoscopists were included. APC showed a strong correlation with ADR (r = 0.94; P < .01), and both showed a similar correlation with the advanced ADR (ADR: r = 0.47; P < 0.01, APC: r = 0.46; P < .01). APP showed weaker correlations compared with all other parameters (ADR: r = 0.36; P < .01; advanced ADR: r = 0.19; P < .01). Private practices did not differ in ADR, APP or APC from hospitals. Among endoscopists with ADRs of ≥25%, 7 (10.3%) had an APP in the lowest quartile, whereas no endoscopists had an APC in the lowest quartile. CONCLUSIONS: APC did not reveal additional information to ADR, and thus there is no need to use it instead of or additionally to ADR. Although the APP identifies endoscopists who find few adenomas per procedure despite acceptable ADRs, this additional information might not be important in regard to sufficient colorectal cancer prevention, because these endoscopists still had high advanced ADRs.

An analysis of four different methods of producing focal cerebral ischemia with endothelin-1 in the rat.

Endothelin-1 (ET-1), a potent vasoconstrictor, reduces local blood flow to levels that produce ischemic injury when injected directly into brain tissue. The purpose of this study was to compare 4 different methods of inducing focal ischemia with ET-1: (1) topical application to the forelimb motor region of the cortex, (2) intracerebral injection into the forelimb motor region of the cortex, (3) a combination of intracortical and intrastriatal injections and 4. injection of ET-1 adjacent to the middle cerebral artery (MCA). We examined the effect of delivery method and dose of ET-1 on lesion size, inter-animal variability and behavioral outcome on 3 separate tests of motor function and limb preference. We calculated success rate as the percentage of animals that survived surgery and developed a significant impairment (>20% decrease in performance post-surgery) in the staircase-reaching test. All 4 methods produced similar deficits in the staircase, balance beam, and cylinder tests, but the application of ET-1 adjacent to the MCA, though widely used, provided the lowest success rate. The combined cortical and striatal ET-1 produced a high success rate and consequently we examined cerebral blood flow (CBF), the apparent diffusion coefficient (ADC) and T2-weighted magnetic resonance imaging (MRI) changes for this model. We found that infarct volume measured using T2-weighted MRI correlated with histological measurements and that ADC and CBF together predicted which areas will suffer permanent injury. The combined cortical and striatal injection model offers a number of advantages for studies of recovery of function.

Minocycline and intracerebral hemorrhage: influence of injury severity and delay to treatment.

Intracerebral hemorrhage (ICH) is a devastating condition currently lacking a defined line of treatment. The inflammatory response that ensues following its onset is thought to contribute to secondary injury following ICH, making inflammation a potential therapeutic target. Minocycline (MC), a commonly used antibiotic that also has anti-inflammatory and anti-apoptotic properties, provides histological protection in several animal stroke models when given soon after injury. However, its ability to provide protection with more clinically relevant delays is unknown. The objective of this study was to examine the effects of MC on histopathological changes and long-term functional outcomes in a collagenase-induced ICH model in rats when drug administration was delayed 3 h following the onset of ICH. In accordance with other studies, MC suppressed microglial/macrophage activation in the peri-infarct region at 5 days based on B4 isolectin histochemistry. However, no reduction in infarct volume was detected at 5 or 28 days post-ICH. Minocycline given for either 5 or 14 days also provided no functional benefit as assessed with a battery of sensory-motor tests (i.e., staircase, cylinder, ladder tests). These findings raise questions about the ability of MC to provide protection in ICH when delay to treatment is increased.

Bi-hemispheric contribution to functional motor recovery of the affected forelimb following focal ischemic brain injury in rats.

In many recovering hemiparetic stroke patients, movement of the affected limb elicits ipsilateral activation of sensorimotor areas within the undamaged hemisphere, which is not observed in control subjects. Following middle cerebral artery occlusion, rats received intensive enriched-rehabilitation (ER) of the impaired forelimb for 4 weeks. Weekly assessments on a skilled reaching test demonstrated significant improvement in ischemic animals over 4 weeks of ER (P < 0.05). We hypothesized that if the undamaged forelimb motor cortex contributed to improved forelimb function, then inhibition of neural activity within this region should reinstate (at least some of) the initial motor impairment. After 3 and 4 weeks of ER, animals received a microinjection of lidocaine hydrochloride into the undamaged motor cortex and were re-assessed on reaching ability. The behavioral effect of lidocaine challenge was dependent on the size of the infarct: animals with large infarcts were rendered unable to retrieve any food pellets and had great difficulty even contacting a pellet with the affected forepaw. Small-infarct animals were only moderately affected (25% reduction in success) by lidocaine, an effect similar to that observed in control animals. Qualitative assessments of recovered reaching after 4 weeks of rehabilitation revealed that impairments in forelimb lift, advance and aim were exacerbated (P < 0.05) following lidocaine-inactivation of the undamaged motor cortex of animals with large ischemic infarcts. In animals with small infarcts, lidocaine challenge only impaired limb advance. Thus, recruitment of the undamaged hemisphere may depend on the functional integrity of the remaining sensorimotor system. These data suggest that, in the rat, the undamaged (ipsilateral) motor system may contribute to compensatory recovery of the affected forelimb.

Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral haemorrhage in mice.

We investigated the role of matrix metalloproteinases (MMPs) in a mouse model of intracerebral haemorrhage (ICH). Transcripts encoding nine of the 23 known mammalian MMPs were measured. MMP-12 levels were the most elevated. To evaluate the role of MMP-12 in ICH, haemorrhages were induced in wild-type (WT) and MMP-12 null mice. The results show that MMP-12 null mice exhibited significant functional recovery of forelimb reaching and reduced dependence on the ipsilateral forelimb compared to WT mice. There was also a trend for improved sensory function in the tape removal test. With respect to single pellet skilled reaching, MMP-12 null mice recovered to a level that was not significantly different from sham at 14 and 28 days post-ICH. In contrast, WT animals demonstrated a persistent impairment relative to sham controls throughout the survival period (P < 0.05). The cylinder task revealed a lesion-induced reliance on the ipsilateral forelimb that was apparent at day 7 in both MMP-12 null and WT mice (P < 0.05), but only persisted in WT mice at 14 days post-ICH (P < 0.05). Differences in functional outcome could not be explained by tissue sparing. However, Iba1 immunostaining indicated that more cells bearing macrophage morphology were recruited to the lesion area in WT mice. This is the first study to profile the expression patterns of a number of the known MMPs following ICH in mice. The data indicate that MMP-12 expression following haemorrhagic stroke is deleterious and contributes to the development of secondary injury in this disease.