Pulmonary Embolism Associated with COVID-19 Occurs in Predominantly Elderly Patients with Comorbidities: A Single Center Retrospective Study.

Introduction: Complications of COVID-19 infection have been greatly investigated. The most recent studies found strong association of COVID-19 pneumonia with thromboembolism. The aim of research was to describe clinical and computed tomography pulmonary angiograms (CTPA) characteristics of COVID-19 related pulmonary artery thromboembolism (PE). Methods: All consecutive CTPA with positive PE in COVID-19 patients from University Hospital Split, from March 23, 2020 to January 31, 2021 were analyzed. Baseline data were collected from patient's electronic records. CTPA scan analysis identified PE anatomical location (i.e., main, lobar, segmental, or subsegmental). Results: A total number of 78 positive CTPA in COVID-19 patients was mainly in elderly with several co-morbidities, high D-dimer levels, at median of 14 days. CTPAs showed involvement of the entire pulmonary artery tree, mainly of the small-to medium diameter pulmonary artery branches, unilaterally (n = 31, 39,74%), and bilaterally (n = 33, 42.31%). The large-diameter branches were the most rarely affected as a single location (n = 14, 17.95%). Conclusion: PE occurred in predominantly elderly people, having several comorbidities, and high D-dimer levels. Embolic involvement of pulmonary branches of all sizes were found, the most frequent of small to medium diameter branches. Further investigation is needed to better understand mechanisms and course of the COVID-19 related PE.

Predictive value of abdominal drain amylase for postoperative pancreatic fistula following gastric resection: A systematic review and meta-analysis.

BACKGROUND: Radical dissection of lymph nodes, accompanying gastric cancer resection, can lead to collateral damage to the pancreas and development of postoperative pancreatic fistula (POPF). METHODS: We searched the Cochrane Library, MEDLINE, Embase, and Web of Science up to April 21, 2020, to identify studies documenting the value of abdominal drain amylase level (d-AMY) on postoperative day 1 (POD1) as a predictor of POPF after gastric surgery. The quality of selected studies was assessed using the QUADAS-2 tool. The diagnostic value of d-AMY on POD1 for prediction of POPF was first assessed by calculation of pooled estimates of sensitivity, specificity, likelihood ratios (LR), and the diagnostic odds ratio (DOR). Secondly, the accuracy was further demonstrated graphically with the hierarchical summary receiver operating curve (hSROC). PROSPERO registration number: CRD42020181145. RESULTS: DOR of nine studies (cases n = 1856) observing the occurrence of POPF after measurement of d-AMY on POD1 was 18.7 (95%CI: 10.0, 34.8), and the area under hSROC was 0.88 ± 0.02. The pooled sensitivity was 0.74 (95%CI: 0.66, 0.81) and specificity 0.84 (95%CI: 0.82, 0.86). The negative LR was at the lowest point of 0.16 (95%CI: 0.07, 0.37) at the cutoff value for d-AMY of 941 IU/L, while the positive LR ranged from 4.4 (cutoff 2119 IU/L) to 6.2 (cutoff 5000 IU/L). CONCLUSION: d-AMY on POD1 can be used as an accurate and non-invasive predictor of POPF in the earliest stage of postoperative course following gastric cancer resection; value ≤ 941 IU/L warrants early drain removal and low probability of POPF (any grade).

Adequacy of risk of bias assessment in surgical vs non-surgical trials in Cochrane reviews: a methodological study.

BACKGROUND: Bias in randomized controlled trials (RCTs) can lead to underestimation or overestimation of the true effects of interventions. Surgical RCTs may suffer from the risk of bias (RoB) that is avoidable in trials of other interventions, and vice versa. We aimed to compare the adequacy of RoB assessments in surgical versus non-surgical RCTs included in Cochrane reviews and to assess the most common differences in those RoB assessments. Due to specificities of surgical trials, i.e. difficulties associated with blinding of surgical interventions, we hypothesized that assessments of surgical trials may be more adequate, compared to RCTs of non-surgical interventions. METHODS: This was a methodological study, analyzing methods of published Cochrane systematic reviews. Data were extracted from RoB tables in Cochrane reviews (judgments and accompanying explanatory comment) for the following four RoB domains used in the 2011 Cochrane RoB tool: randomization, allocation concealment, blinding of participants and personnel, and blinding of outcome assessors. We defined adequate assessments as those that were in line with instructions from the Cochrane Handbook for Systematic Reviews of Interventions. The prevalence of adequate assessments was compared in surgical versus non-surgical trials. The most common differences in both groups of reviews were presented. RESULTS: In 729 analyzed Cochrane reviews, there were 10,537 included trials. The prevalence of adequate RoB judgments made by Cochrane authors ranged from 87.9, 95%CI (87.3 to 88.6%) for randomization to 70.7, 95%CI (69.8 to 71.5%) for blinding of participants and personnel. For all analyzed RoB domains, the prevalence of adequate RoB domains was higher in surgical trials than in non-surgical trials. For two RoB domains assessing blinding, this difference between surgical and non-surgical trials was statistically significant (P < 0.001), while the difference was not significant for the RoB domain regarding randomization (P = 0.124) and allocation concealment (P = 0.039, ß < 0.8). CONCLUSIONS: RoB judgments were more in line with instructions from the Cochrane Handbook when Cochrane reviews assessed surgical trials, compared to those that analyzed non-surgical interventions. However, further steps are warranted to scrutinize RoB assessment in trials of both surgical and non-surgical interventions.

Assessing risk of bias judgments for blinding of outcome assessors in Cochrane reviews.

Aim: Adequate judging of risk of bias (RoB) for blinding of outcome assessors (detection bias) is important for supporting highest level of evidence. Materials & methods: Judgments and supporting comments for detection bias were retrieved from RoB tables reported in Cochrane reviews. We categorized comments, and then compared judgment and supporting comment with instructions from the Cochrane Handbook. Results: We analyzed 8656 judgments for detection bias from 7626 trials included in 575 reviews. Overall, 1909 judgments (22%) were not in line with the Cochrane Handbook. In 9% of trials, the authors split the detection bias domain according to outcomes. Here, prevalence of inadequate judgments was 19%. Conclusion: Interventions to improve RoB assessments in systematic reviews should be explored.

Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes.

Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle. Left ventricular myocardium from 37 patients (a group of patients with diabetes and a group of patients without diabetes [ejection fraction >50%]) undergoing coronary artery bypass graft surgery was obtained by subepicardial needle biopsy. The group with diabetes had a significantly decreased rate of mitochondrial respiration fueled by palmitoyl-carnitine that correlated with blood glucose dysregulation, while there was no difference in oxidation of pyruvate. Diabetic myocardium also had significantly decreased activity of hydroxyacyl-CoA dehydrogenase (HADHA) and accumulated more lipid droplets and ceramide. Also, markers of ER stress response (GRP78 and CHOP) and apoptosis (cleaved caspase-3) were elevated in diabetic myocardium. These results show that, even in the absence of contractile failure, diabetic heart exhibits a decreased mitochondrial capacity for ß-oxidation, increased accumulation of intracellular lipids, ER stress, and greater degree of apoptosis. Lower efficiency of mitochondrial fatty acid oxidation may represent a potential target in combating negative effects of diabetes on the heart.

Risk of bias judgments for random sequence generation in Cochrane systematic reviews were frequently not in line with Cochrane Handbook.

BACKGROUND: Assessing the risk of bias (RoB) in included studies is one of the key methodological aspects of systematic reviews. Cochrane systematic reviews appraise RoB of randomised controlled trials (RCTs) with the Cochrane RoB tool. Detailed instructions for using the Cochrane RoB tool are provided in the Cochrane Handbook for Systematic Reviews of Interventions (The Cochrane Handbook). The purpose of this study was to analyse whether Cochrane authors use adequate judgments about the RoB for random sequence generation of RCTs included in Cochrane reviews. METHODS: We extracted authors' judgments (high, low or unclear RoB) and supports for judgments (comments accompanying judgments which explain the rationale for a judgment) for random sequence generation of included RCTs from RoB tables of Cochrane reviews using automated data scraping. We categorised all supporting comments, analysed the number and type of various supporting comments and assessed adequacy of RoB judgment for randomisation in line with recommendations from the Cochrane Handbook. RESULTS: We analysed 10,103 RCTs that were included in 704 Cochrane reviews. For 5,706 RCTs, randomisation was not described, but for the remaining RCTs, it was indicated that randomisation was performed using computer/software/internet (N = 2,850), random number table (N = 883), mechanical method (N = 359) or it was incomplete/inappropriate (N = 305). Overall, 1,220/10,103 trials (12%) did not have a RoB judgment in line with Cochrane Handbook guidance about randomisation. The highest proportion of misjudgements was found for trials with high RoB (28%), followed by those with low (20%) or unclear (3%). Therefore, one in eight judgments for the analysed domain in Cochrane reviews was not in line with Cochrane Handbook, and one in four if the judgment was "high risk". CONCLUSION: Authors of Cochrane reviews often make judgments about the RoB related to random sequence generation that are not in line with instructions given in the Cochrane Handbook, which compromises the reliability of the systematic reviews. Our results can help authors of both Cochrane and non-Cochrane reviews which use Cochrane RoB tool to avoid making common mistakes when assessing RoB in included trials.

Risk of bias assessments for blinding of participants and personnel in Cochrane reviews were frequently inadequate.

OBJECTIVES: The objective of this study was to analyze adequacy of judgments about risk of bias (RoB) for blinding of participants and personnel (performance bias) in Cochrane systematic reviews of randomized controlled trials (RCTs). STUDY DESIGN AND SETTING: We extracted judgments and supporting comments for performance bias from Cochrane reviews' RoB tables using automated data scraping. We parsed all intervention descriptions, judgments about risk of performance bias, and comments supporting judgments into simple categories. We assessed adequacy of RoB judgments against recommendations from the Cochrane Handbook. RESULTS: We analyzed judgments for performance bias of 10,429 RCTs included in 718 Cochrane reviews. Overall, 1,828 out of 6,918 judgments (26%) for performance bias were not in line with the Cochrane Handbook and were therefore considered inadequate. In reviews where Cochrane authors have split the performance bias domain into two subdomains, based on blinded individuals, we found lower prevalence of inadequate risk of bias judgments, with 9% of judgments for blinding of participants, and 5.8% judgments for the blinding of personnel subdomain being judged inadequately. CONCLUSION: In Cochrane reviews, risk of bias assessments for blinding of participants and personnel were frequently not in line with Cochrane Handbook recommendations. Interventions to improve these assessments should be taken into consideration.

Outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain in children and adolescents.

BACKGROUND: We analysed outcome domains and pain outcome measures in randomized controlled trials of interventions for postoperative pain management in children and adolescents and compared them to the core outcome set recommended by the Pediatric Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (PedIMMPACT). METHODS: Systematic literature search was conducted in MEDLINE, CDSR, DARE, CINAHL and PsycINFO up to 31 January 2017. One author extracted data and second verified the extraction. Outcome domains and pain outcome measures were analysed and compared with the PedIMMPACT core outcome set. RESULTS: We included 337 trials. Median number of reported outcomes was five (range 1-11) for the included trials and two (range 0-6) for PedIMMPACT. The most commonly analysed PedIMMPACT outcome domains were pain intensity (93%) and "symptoms and adverse events" (83%). The remaining four PedIMMPACT outcomes were present in under 30% of included randomized controlled trials. Proportion of PedIMMPACT outcome domains did not change after the PedIMMPACT was published in 2008. Of the 312 trials that reported pain intensity, 303 (97%) also specified pain assessment tools, in which the most common was the visual analogue scale (24%) followed by the Children's Hospital of Eastern Ontario Pain Scale (18%). CONCLUSION: Analysed trials about interventions for pediatric postoperative pain insufficiently used the recommended core outcome set for acute pain in children. Relevance of the PedIMMPACT core outcome set, as well as the reasons behind its limited uptake, need to be further evaluated. SIGNIFICANCE: Recommended core outcomes have been insufficiently used in randomized controlled trials about postoperative pain in children, which hinders comparability of studies and makes synthesis of evidence difficult.

Authors' lack of awareness and use of core outcome set on postoperative pain in children is hindering comparative effectiveness research.

AIM: To analyze awareness about and acceptability of core outcome set (COS) for pediatric pain recommended by the PedIMMPACT. METHODS: We invited authors of systematic reviews and randomized controlled trials about interventions for postoperative pain in children to participate in a survey. RESULTS: Only a third of surveyed authors of systematic reviews and randomized controlled trials about postoperative pain in children had heard about the PedIMMPACT COS for acute pediatric pain. Problems indicated as preventing them from using the COS were lack of awareness, difficulties with implementation, and lack of resources. CONCLUSION: Further discussions about the adequacy of COS for acute pediatric pain, as well as interventions to increase the uptake of COS may be warranted.

Expression of Mitochondrial Respiratory Chain Complexes in the Vaginal Wall in Postmenopausal Women with Pelvic Organ Prolapse.

BACKGROUND/AIMS: Pelvic organ prolapse (POP) is a common disease affecting adult women. It is a result of the vaginal wall disorder as well as damage of the supportive structures contributing to the integrity of the pelvic floor. Mitochondrial disorders may have an important role in the vaginal wall degeneration leading to POP. The goal of this research is to examine if POP is associated with an altered expression of mitochondrial respiratory chain complexes. METHODS: Samples of vaginal tissue were collected from 16 postmenopausal women: 10 had POP and 6 had other forms of benign gynecological disease. Using western blot, samples were analyzed to assess the expression of mitochondrial proteins including citrate synthase (CS), individual complexes of the mitochondrial respiratory chain and alpha smooth muscle actin (SMA). RESULTS: A significantly reduced expression of SMA and complex II in vaginal tissue of women with POP was found, compared to the control group (p < 0.05), with a tendency for a reduced expression of CS (p = 0.06) and other complexes in the POP group. CONCLUSIONS: Our results indicate that there is a decreased quantity of the smooth muscle and a decreased expression of mitochondrial markers in the vaginal wall of women with prolapse suggesting their possible role in the pathogenesis of POP.

Interventions for postoperative pain in children: An overview of systematic reviews.

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti-inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non-Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.

Interventions for Neuropathic Pain: An Overview of Systematic Reviews.

Numerous interventions for neuropathic pain (NeuP) are available, but its treatment remains unsatisfactory. We systematically summarized evidence from systematic reviews (SRs) of randomized controlled trials on interventions for NeuP. Five electronic databases were searched up to March 2015. Study quality was analyzed using A Measurement Tool to Assess Systematic Reviews. The most common interventions in 97 included SRs were pharmacologic (59%) and surgical (15%). The majority of analyzed SRs were of medium quality. More than 50% of conclusions from abstracts on efficacy and approximately 80% on safety were inconclusive. Effective interventions were described for painful diabetic neuropathy (pregabalin, gabapentin, certain tricyclic antidepressants [TCAs], opioids, antidepressants, and anticonvulsants), postherpetic neuralgia (gabapentin, pregabalin, certain TCAs, antidepressants and anticonvulsants, opioids, sodium valproate, topical capsaicin, and lidocaine), lumbar radicular pain (epidural corticosteroids, repetitive transcranial magnetic stimulation [rTMS], and discectomy), cervical radicular pain (rTMS), carpal tunnel syndrome (carpal tunnel release), cubital tunnel syndrome (simple decompression and ulnar nerve transposition), trigeminal neuralgia (carbamazepine, lamotrigine, and pimozide for refractory cases, rTMS), HIV-related neuropathy (topical capsaicin), and central NeuP (certain TCAs, pregabalin, cannabinoids, and rTMS). Evidence about interventions for NeuP is frequently inconclusive or completely lacking. New randomized controlled trials about interventions for NeuP are necessary; they should address safety and use clear diagnostic criteria.

Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia.

KEY POINTS: The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery-jugular venous oxygen content difference, was reduced by ∼29% at the termination of apnoea, although there was no change in the non-oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia-induced oxygen-conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. ABSTRACT: Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2 ) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea-divers performed a maximal apnoea (range 3 min 36 s to 7 min 26 s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2  was reduced by ∼29% (P < 0.01, Cohen's d = 1.18) near the termination of apnoea compared to baseline, although non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ∼38.4 mmHg), severe hypercapnia (arterial CO2 tension: ∼58.7 mmHg), but not mild-hypercapnia (arterial CO2 tension: ∼46.3 mmHg), depressed the CMRO2 (∼17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnoea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea.