Toenail Manganese: A Sensitive and Specific Biomarker of Exposure to Manganese in Career Welders

Manganese (Mn) is an essential trace metal. It is also a component of welding fume. Chronic inhalation of manganese from welding fume has been associated with decreased neurological function. Currently, there is not a universally recognized biomarker for Mn exposure; however, hair and toenails have shown promise. In a cohort of 45 male welders and 35 age-matched factory control subjects, we assessed the sensitivity and specificity of toenail Mn to distinguish occupationally exposed subjects from unexposed controls. Further we examined the exposure time window that best correlates with the proposed biomarker, and investigated if non-occupational exposure factors impacted toenail Mn concentrations. Toenail clippings were analyzed for Mn using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Exposure to respirable Mn-containing particles (<4 µm) was estimated using an exposure model that combines personal air monitoring, work history information, and dietary intake to estimate an individual's exposure to Mn from inhalation of welding fume. We assessed the group differences in toenail concentrations using a Student's t-test between welders and control subjects and performed a receiver operating characteristic (ROC) curve analysis to identify a threshold in toenail concentration that has the highest sensitivity and specificity in distinguishing welders from control subjects. Additionally, we performed mixed-model regressions to investigate the association between different exposure windows and toenail Mn concentrations. We observed that toenail Mn concentrations were significantly elevated among welders compared to control subjects (6.87 ± 2.56 versus 2.70 ± 1.70 µg g-1; P < 0.001). Our results show that using a toenail Mn concentration of 4.14 µg g-1 as cutoff allows for discriminating between controls and welders with 91% specificity and 94% sensitivity [area under curve (AUC) = 0.98]. Additionally, we found that a threshold of 4.66 µg g-1 toenail Mn concentration enables a 90% sensitive and 90% specific discrimination (AUC = 0.96) between subjects with average exposure above or below the American Conference of Governmental Industrial Hygienist (ACGIH) Threshold Limit Value (TLV) of 0.02 mg m-3 during the exposure window of 7-12 months prior to the nail being clipped. Investigating which exposure window was best reflected by toenail Mn reproduced the result from another study of toenail Mn being significantly (P < 0.001) associated with exposure 7-12 months prior to the nail being clipped. Lastly, we found that dietary intake, body mass index, age, smoking status, and ethnicity had no significant effect on toenail Mn concentrations. Our results suggest that toenail Mn is a sensitive, specific, and easy-to-acquire biomarker of Mn exposure, which is feasible to be used in an industrial welder population

Molecular and serological techniques for the diagnosis of culture negative infective endocarditis in Alexandria Main University Hospital

AbstractBackground and aimCulture-negative infective endocarditis (CNIE) is a diagnostic dilemma. The study was carried out to estimate the prevalence of CNIE among definite IE cases, to describe the epidemiologic and clinical characteristics of CNIE patients and to diagnose the microbial etiology of CNIE using molecular and serological techniques.Subjects and methodsSixty-five definite IE cases were enrolled in a prospective observational study between January and December 2010. CNIE cases were tested by 16SrRNA and seminested PCR for 35 blood samples, serological tests and the study of ten valve tissue specimens.ResultsCNIE constituted 39 (60%) cases. The mean age of CNIE patients was 31years. Male to female ratio was 2.9:1. Healthcare associated IE accounted for 15.4%, native valve IE for 66.7% and intravenous drug abuse for 20.5% of cases. The mitral valve was the most frequently involved (56.4%). Out of 39 CNIE cases, seminested blood PCR detected 12 cases (ten Staphylococci, two Streptococci). Five cases were reactive by serology (three Bartonella, one Coxiella, and one Brucella). Six cases were positive by analysis of valve tissue (three Staphylococci, three Streptococci). The combined results of all diagnostic tools decreased the percentage of non-identified causes of CNIE from 60% to 24.6%.ConclusionsOur data underlined the role of collecting blood culture before starting antibiotics and the role of seminested PCR in the diagnosis of conventional causes of CNIE. The importance of serology to identify non conventional causes was also highlighted

Mechanical Thrombectomy for Acute Ischemic Stroke in Metastatic Cancer Patients: A Nationwide Cross-Sectional Analysis

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is the standard treatment for large vessel occlusion (LVO) acute ischemic stroke. Patients with active malignancy have an increased risk of stroke but were excluded from MT trials. METHODS: We searched the National Readmission Database for LVO patients treated with MT between 2016-2018 and compared the characteristics and outcomes of cancer-free patients to those with metastatic cancer (MC). Primary outcomes were all-cause in-hospital mortality and favorable outcome, defined as a routine discharge to home (regardless of whether home services were provided or not). Multivariate regression was used to adjust for confounders. RESULTS: Of 40,537 LVO patients treated with MT, 933 (2.3%) had MC diagnosis. Compared to cancer-free patients, MC patients were similar in age and stroke severity but had greater overall disease severity. Hospital complications that occurred more frequently in MC included pneumonia, sepsis, acute coronary syndrome, deep vein thrombosis, and pulmonary embolism (P\u3c0.001). Patients with MC had similar rates of intracerebral hemorrhage (20% vs. 21%) but were less likely to receive tissue plasminogen activator (13% vs. 23%, P\u3c0.001). In unadjusted analysis, MC patients as compared to cancer-free patients had a higher in-hospital mortality rate and were less likely to be discharged to home (36% vs. 42%, P=0.014). On multivariate regression adjusting for confounders, mortality was the only outcome that was significantly higher in the MC group than in the cancerfree group (P\u3c0.001). CONCLUSION: LVO patients with MC have higher mortality and more infectious and thrombotic complications than cancer-free patients. MT nonetheless can result in survival with good outcome in slightly over one-third of patients

Association of serum leptin and ghrelin levels with smoking status on body weight: a systematic review and meta-analysis

Background and aimsSmoking cigarettes is a major global health problem that affects appetite and weight. The aim of this systematic review was to determine how smoking affected plasma leptin and ghrelin levels.MethodsA comprehensive search of PubMed, Scopus, Web of Science, and Ovid was conducted using a well-established methodology to gather all related publications.ResultsA total of 40 studies were included in the analysis of 11,336 patients. The overall effect showed a with a mean difference (MD) of −1.92[95%CI; −2.63: −1.20] and p = 0.00001. Subgroup analysis by study design revealed significant differences as well, but with high heterogeneity within the subgroups (I2 of 82.3%). Subgroup by sex showed that there was a significant difference in mean difference between the smoking and non-smoking groups for males (MD = −5.75[95% CI; −8.73: −2.77], p = 0.0002) but not for females (MD = −3.04[95% CI; −6.6:0.54], p = 0.10). Healthy, pregnant, diabetic and CVD subgroups found significant differences in the healthy (MD = −1.74[95% CI; −03.13: −0.35], p = 0.01) and diabetic (MD = −7.69[95% CI, −1.64: −0.73], p = 0.03). subgroups, but not in the pregnant or cardiovascular disease subgroups. On the other hand, the meta-analysis found no statistically significant difference in Ghrelin serum concentration between smokers and non-smokers (MD = 0.52[95% CI, −0.60:1.63], p = 0.36) and observed heterogeneity in the studies (I2 = 68%).ConclusionThis study demonstrates a correlation between smoking and serum leptin/ghrelin levels, which explains smoking’s effect on body weight.Systematic review registrationhttps://www.crd.york.ac.uk/ prospero/display_record.php, identifier (Record ID=326680)

Longitudinal changes in peri-papillary retinal nerve fiber layer thickness in patients with unilateral branch retinal vein occlusion

Background: Associations between retinal venous occlusion (RVO), elevated intraocular pressure, and glaucoma have been reported. Further investigations into structural alterations in the fellow eyes of individuals with unilateral RVO have revealed that the peripapillary retinal nerve fiber layer is thinner than in healthy eyes, suggesting that there may be systemic risk factors common to both RVO and glaucoma. We aimed to evaluate changes in peripapillary retinal nerve fiber layer thickness (pRNFLT) among individuals with unilateral branch retinal vein occlusion (BRVO). Methods: This prospective observational study recruited 30 individuals (60 eyes) with newly diagnosed unilateral BRVO and macular edema, and a control group of 30 healthy individuals (30 eyes) with no abnormalities on fundus examination or concurrent systemic comorbidities. After baseline measurements, the participants were reassessed at 6, 12, and 24 months by measuring global and sectoral pRNFLT using spectral-domain optical coherence tomography. Results: The mean age and sex distributions were comparable between the patient and control groups (both P &gt; 0.05). When compared to fellow eyes, global and sectoral pRNFLT in eyes with BRVO were significantly higher at baseline (all P &lt; 0.05). Over time, pRNFLT decreased dramatically, and by the conclusion of the two-year follow-up, there was a significant reduction from baseline in the affected eyes (all P &lt; 0.05). Likewise, affected eyes experienced a significant improvement in best-corrected distance visual acuity and central macular thickness over the two-year follow-up (both P Less than or equal to 0.001). Comparing the global and all-sector pRNFLT of fellow eyes in the patient group with those of normal eyes in the control group, there were no significant differences at any visit, except in the temporal sector, which revealed a significant reduction in pRNFLT at 24 months in the fellow eyes of patients with unilateral BRVO (P = 0.02).&nbsp;&nbsp; Conclusions: Patients with unilateral BRVO experienced a significant reduction in pRNFLT in the affected eyes and, to a lesser extent, in the fellow eyes, compared with that of the control arm, suggesting that they are prone to retinal nerve fiber layer damage. The reduction in pRNFLT in the normal fellow eyes of patients with BRVO may be attributed to age or concurrent systemic comorbidities. Further studies with long follow-up periods are required to shed light on the etiology of functional and structural changes in both the retinal nerve fiber layer and ganglion cell complex in the normal and affected eyes of patients with unilateral BRVO

Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl chromene-3-carbaldehyde derivatives

Novi hidrazono- 5a,b, tiosemikarbazono- 6a-c i oksimo kromeni 7a-c sintetizirani su iz odgovarajućeg β-klorkarbaldehida 3 i hidrazina, aromatskog hidrazina, tiosemikarbazida ili hidroksilamin hidroklorida, dok su eterski derivati 8a-h pripremljeni iz pripadajućih aldoksima 7a-c. Novi spojevi ispitani su na protuupalno i ulcerogeno djelovanje, a njihovo djelovanje uspoređeno je s djelovanjem indometacina.Some new hydrazono- 5a,b, thiosemicarbazono- 6a-c, and oximo chromenes 7a-c were prepared via the reaction of the corresponding β-chlorocarbaldehyde 3 with hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride, respectively. In addition, ether derivatives 8a-h were prepared from the corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory and ulcerogenic score activities compared to indomethacin

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely