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Kay Por Yip,1 Robert A Stockley,2 Elizabeth Sapey1 1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, UK; 2Department of Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Edgbaston, Birmingham, UKCorrespondence: Kay Por Yip Email K.P.Yip@bham.ac.ukAbstract: Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality worldwide. Despite this, there has been little progress so far in terms of disease-modifying therapies over the last few decades and this is in part due to poor understanding of the definition and mechanisms surrounding early disease before it becomes established and increasingly complex. In this review, the nuances and difficulty in defining early disease in COPD are discussed. There are clear benefits in identifying patients early; however, usually diagnosis is made in the presence of significant lung damage. We consider what can be learned of early disease from COPD studies and highlight the lack of inclusion of young smokers (who may be at risk of COPD) or those with mild disease. We discuss promising clinical measures that are being used in an effort to detect early disease. These include symptom assessment, lung physiology measures and computed tomography (CT) imaging modalities. There is emerging evidence for the role of neutrophils and their proteinases in early COPD. This may form an important biomarker to investigate the pathophysiological processes of early COPD. Given the importance of the early disease, it is recommended that future COPD studies focus on capturing the earliest manifestations of disease, to understand the initiating mechanisms and to identify novel treatment targets.Keywords: COPD, early, neutrophil, lung function, biomarker

During the acute phase of myocardial infarction, the culprit artery must be revascularized quickly with angioplasty. Surgery then completes the procedure in a second stage. If emergency surgery is performed, the resulting death rate is high; 15–20% of patients are operated on within the first 48 h after the myocardial infarction. The timing of surgical revascularization and the patient’s preoperative state influence the mortality rate. We aimed to evaluate the impact of surgery delay on morbimortality. Between 2007 and 2017, a retrospective monocentric study was conducted including 477 haemodynamically stable patients after myocardial infarction who underwent an urgent coronary bypass. Three groups were described, depending on the timing of the surgery: during the first 4 days (Group 1, n = 111, 23%), 5 to 10 days (Group 2, n = 242, 51%) and after 11 days (Group 3, n = 124, 26%). The overall thirty-day mortality was 7.1% (n = 34). The death rate was significantly higher in Group 1 (n = 16; 14% vs. n = 10; 4.0% vs. n = 8; 6%, p < 0.01). The mortality risk factors identified were age (OR: 1.08; CI 95%: 1.04–1.12; p < 0.001), peripheral arteriopathy (OR: 3.31; CI 95%: 1.16–9.43; p = 0.024), preoperative renal failure (OR: 6.39; CI 95%: 2.49–15.6; p < 0.001) and preoperative ischemic recurrence (OR: 3.47; CI 95%: 1.59–7.48; p < 0.01). Ninety-two patients presented with preoperative ischemic recurrence (19%), with no difference between the groups. The optimal timing for the surgical revascularization of MI seems to be after Day 4 in stable patients. However, timing is not the only factor influencing the death rate: the patient’s health condition and disease severity must be considered in the individual management strategy.

Lung cancer is a leading cause of cancer deaths and early diagnosis can significantly improve outcomes. Pathogenic bacteria have been shown to play a role in tumorigenesis and its analysis provides a new approach for cancer diagnosis. To evaluate the potential of bacteria as plasma biomarkers for early lung cancer detection, we analyzed eight lung-cancer-related bacterial genera in 58 lung cancer patients and 58 controls using ddPCR. Our results showed that five genera had higher DNA abundance in lung tumor tissues compared with normal tissues. Three of these genera (Selenomonas, Streptococcus, and Veillonella) displayed consistent changes in plasma, with higher DNA abundance in lung cancer patients compared with controls. When used as a panel, these three bacterial genera had a sensitivity of 75% and specificity of 78% for lung cancer detection, regardless of stage or histology. The performance of this biomarker panel was confirmed in an independent cohort of 93 lung cancer cases and 93 controls. Thus, circulating bacterial DNA has the potential to be used as plasma biomarkers for early lung cancer detection.

Background: Despite differences in time of sepsis recognition, recent studies support that early initiation of norepinephrine in patients with septic shock (SS) improves outcome without an increase in adverse effects. This study aims to investigate the relationship between 30-day mortality in patients with SS and prehospital norepinephrine infusion in order to reach a mean blood pressure (MAP) > 65 mmHg at the end of the prehospital stage.Methods: From April 06th, 2016 to December 31th, 2020, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To consider cofounders, the propensity score method was used to assess the relationship between prehospital norepinephrine administration in order to reach a MAP > 65 mmHg at the end of the prehospital stage and 30-day mortality.Results: Four hundred and seventy-eight patients were retrospectively analysed, among which 309 patients (65%) were male. The mean age was 69 ± 15 years. Pulmonary, digestive, and urinary infections were suspected among 44%, 24% and 17% patients, respectively. One third of patients (n = 143) received prehospital norepinephrine administration with a median dose of 1.0 [0.5-2.0] mg h-1, among which 84 (69%) were alive and 38 (31%) were deceased on day 30 after hospital-admission. 30-day overall mortality was 30%. Cox regression analysis after the propensity score showed a significant association between prehospital norepinephrine administration and 30-day mortality, with an adjusted hazard ratio of 0.42 [0.25-0.70], p < 10-3. Multivariate logistic regression of IPTW retrieved a significant decrease of 30-day mortality among the prehospital norepinephrine group: ORa = 0.75 [0.70-0.79], p < 10-3.Conclusion: In this study, we report that prehospital norepinephrine infusion in order to reach a MAP > 65 mmHg at the end of the prehospital stage is associated with a decrease in 30-day mortality in patients with SS cared for by a MICU in the prehospital setting. Further prospective studies are needed to confirm that very early norepinephrine infusion decreases septic shock mortality. [ABSTRACT FROM AUTHOR]

Background: Uncontested air movement and advances for medical care of combat casualties have resulted in a decreased case fatality rate. However, in future large-scale combat operations, the military has established a plan for multidomain operations to defeat near-peer adversaries. Prolonged casualty care and mass casualty scenarios will become more prevalent. Prehospital friendly scoring systems such as the shock index (SI) and revised trauma score (RTS) may provide useful triage data. Development of accurate, data-driven, triage systems will be key to optimize management of resources, care, and transport of combat casualties. Methods: We included data from the Department of Defense Trauma Registry between 01 January 2007 to 17 March 2020. Data comprised of adult US military or coalition service members for analysis as the baseline cohort, and those who died within 24 hours were included in the early death cohort. We performed statistical analysis on demographics and injury data, SI and RTS to measure the receiver operating characteristics (ROC) of each value to predict early death. Results: The early death cohort had a significantly higher injury severity score (25 vs. 5) and a higher percentage of serious injuries in every body region than the baseline cohort. The early death cohort sustained serious injuries to the head and neck at a rate five times that of the baseline cohort (43.4% vs 8.1%) with odds ratio (OR) of death 8.0 (95% confidence interval 5.7-11.1) followed by skin (13.6% versus 1.9%) with an OR of 6.3 (95% CI 3.8-10.3). The mean SI was 1.21 versus 0.80. The revised trauma score (RTS) was 4.18 versus 7.34. The RTS had a higher area under the receiver operating characteristic (0.896 versus 0.716 for SI). Conclusions: Serious injuries to the head and skin were most strongly associated with death within the first 24 hours. The RTS appears to be a more accurate tool than SI alone for assessing injury mortality. Military medical personnel should consider these factors when triaging casualties during future conflicts in resource limited settings with delayed evacuation. [ABSTRACT FROM AUTHOR]

Background: In adolescents, the rate of meniscal injury at the time of anterior cruciate ligament (ACL) reconstruction, the rate of ACL graft revision, and clinical outcomes has not yet been investigated. Hypothesis: In patients younger than 16 years, the rate of meniscal injuries at the time of ACL reconstruction increases with time from injury. The mid-term revision rate and reoperation rate after ACL reconstruction with hamstrings and lateral tenodesis are lower than those reported in literature for isolate ACL reconstruction. Study Design: Case series. Level of Evidence: Level 4. Methods: Patients younger than 16 years who underwent ACL reconstruction with hamstring and lateral tenodesis, with a follow-up ≥2 years were included. The number of meniscal lesions was stratified according to the delay between injury-to-surgery (<3, 3-12, >12 months). All reoperations, Lysholm score, Knee Injury and Osteoarthritis Outcome Score subscales for pain (at rest and during activity), and return to sport were collected. Results: A total of 151 patients (mean age 14.8 ± 1.2 years) were included. Patients undergoing surgery at <3 months after injury had a lower meniscal injury rate (36%) than those treated at 3 to 12 months (55%) and >12 months (63%) after injury (P = 0.04). Medial meniscal lesions were more likely to be repaired when surgery was performed <3 months after injury (91%). Subjective follow-up data were available for 132 patients, and 19 were lost to follow-up. At 6.0 ± 2.6 years, 6% of patients underwent ACL revision; 1 of 20 (5%) patients with posterior tibial slope ≥12° and 4 of 45 (9%) patients with Tegner level ≥8. Nine new meniscal procedures were performed; 19% of repaired menisci underwent meniscectomy. Good or excellent Lysholm score was reported by 88% of patients; 56% of patients with concurrent lateral meniscectomy had pain during activity, 91% returned to sport, and 79% were still participating at final follow-up. Conclusion: Patients younger than 16 years undergoing ACL reconstruction within 3 months from injury had the lowest rate of meniscal injuries. ACL reconstruction with lateral tenodesis had low revision rate (6%) and good or excellent clinical outcomes in 88% of young adolescents. Clinical Relevance: Sport physicians should be aware that adolescent patients undergoing ACL reconstruction within 3 months after injury have the lowest rate of meniscal injuries; the mid-term revision rate of ACL reconstruction with lateral plasty is lower than 10% and the patients' perceived outcomes are good with almost all patients returning to sport activity. [ABSTRACT FROM AUTHOR]

In spite of multiple therapeutic regimens for vitiligo, disease relapse remains a challenge. Most guidelines consider systemic treatments only in rapidly progressive disease with wider surface areas. This delay in halting the immune attack, may give the chance for further disease progression as well as establishment of resident memory T‐cell population predisposing to future relapses. To assess the ability of early systemic therapy of localized (<2% BSA), recent onset (<6 months) vitiligo to control disease activity and minimize the possibility of recurrence. Twenty‐five patients with recent onset (<6 months), localized (<2% BSA) vitiligo were included. Patients received pulse dexamethasone therapy for 6 months plus topical treatments and NB‐UVB sessions. Patients were followed monthly as regards percent of repigmentation and VIDA score. To detect recurrence, biannual assessment was done for 4 years. Eighty‐four percent of patients had acrofacial lesions and 44% had facial lesions. Arrest of activity was achieved after 3.65 ± 2.19 months. Complete repigmentation was achieved in a mean duration of 6.88 ± 0.2 months. At the end of the 4‐year follow up, recurrence occurred in 32% of patients. In spite of recurrence, localized disease (<2% BSA) was secured. A significantly higher incidence of recurrence was associated with cases with bilateral distribution of lesions. Early systemic immunomodulation for recent localized vitiligo is a successful approach to achieve early control of disease activity and minimize the incidence of recurrence. Such cases should not be overlooked but managed as early as possible; it is a race against time. [ABSTRACT FROM AUTHOR]

Context: Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post–renal transplant hyperglycemia (EPTH) (< 45 days) similarly puts kidney transplant recipients at risk of infections, rehospitalizations, and graft failure and is not emphasized much in the literature. Proactive screening and management of EPTH is required given these consequences. Objective: The aim of this article is to promote recognition of early post-renal transplant hyperglycemia, and to summarize available information on its pathophysiology, adverse effects, and management. Methods: A PubMed search was conducted for “early post–renal transplant hyperglycemia,” “immediate posttransplant hyperglycemia,” “post–renal transplant diabetes,” “renal transplant,” “diabetes,” and combinations of these terms. EPTH is associated with significant complications including acute graft failure, rehospitalizations, cardiovascular events, PTDM, and infections. Conclusion: Patients with diabetes experience better glycemic control in end-stage renal disease (ESRD), with resurgence of hyperglycemia after kidney transplant. Patients with and without known diabetes are at risk of EPTH. Risk factors include elevated pretransplant fasting glucose, diabetes, glucocorticoids, chronic infections, and posttransplant infections. We find that EPTH increases risk of re-hospitalizations from infections (cytomegalovirus, possibly COVID-19), acute graft rejections, cardiovascular events, and PTDM. It is essential, therefore, to provide diabetes education to patients before discharge. Insulin remains the standard of care while inpatient. Close follow-up after discharge is recommended for insulin adjustment. Some agents like dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have shown promise. The tenuous kidney function in the early posttransplant period and lack of data limit the use of sodium-glucose cotransporter 2 inhibitors. There is a need for studies assessing noninsulin agents for EPTH to decrease risk of hypoglycemia associated with insulin and long-term complications of EPTH. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" patients with COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age. [ABSTRACT FROM AUTHOR]

This study aims to measure the level of psychological distress amongst stranded university students due to movement control order (MCO) lockdown in the early stage of a pandemic outbreak. A cross-sectional web-based survey was conducted to obtain prevalence information on perceived depression, anxiety, and stress amongst stranded varsity students in the first 10 days of Malaysia's nationwide lockdown. Information on depression, anxiety and stress was compiled using Depression, Anxiety and Stress Scale-21. Fifty-eight stranded varsity students participated in this survey. The period of research was between the first 2 weeks of the initial MCO enforcement in Malaysia. Descriptive statistics were used to analyse the collected data. 14%, 22% and 10% of the 58 stranded students reported moderate to too severe levels of depression, anxiety and stress, respectively. During this period, the most frequently utilised communication mode with family and loved ones was through phone calls, followed by WhatsApp calls and Facetime. Writing letters and telegram are the least used mode of communication amongst the respondents. Worrying about 'family safety' topped the list as a source of worry that was rated by 88% of the respondents, followed by 'interaction with others' and 'own safety'. Approximately 16% rated 'food and beverage' as a source of stress for them in the first 2 weeks of the lockdown. The government and varsities' coordinated initiatives and measures such as food aid and disseminating essential information by dedicated spokespeople may have softened the negative impact of a pandemic, isolation and uncertain situations on the stranded mental health students.

Abstract Spontaneous JJ stent fragmentation can occur as early as 3 weeks post‐insertion. This could be due to a hostile urine environment and might be avoided by strict dietary modification, adequate hydration, and close follow‐up.

Intraosseous lipoma (IOL) is a benign bone tumor that usually arises from the lower limb and rarely arises from the skull. Radiological diagnosis of a typical case is not problematic due to its characteristic calcification and marginal sclerosis. Here, we report a case of calvarial IOL in the early stage lacking conventional radiopathological features. The patient is a 7-year-old girl who presented with a slow-growing protuberance on the vertex of the head. Computed tomography displayed a low-density mass without calcification that was continuous with the surrounding diploe. The mass was resected piece by piece for diagnostic and cosmetic reasons. Histologically, the specimen consisted of bony trabeculae and intertrabecular adipose tissue, which resembled normal fatty marrow. However, adipose tissue was considered neoplastic since it lacked hematopoietic elements. The final diagnosis of IOL was made by radiopathological correlation. This case suggests that IOL should be included in the differential diagnosis of diploic expansion, even if calcification is absent. The histology of an early-stage IOL resembles normal fatty marrow, but recognizing the absence of hematopoietic elements aids the diagnosis. Also, our literature review indicates that such cases are likely to be encountered in the calvaria than cranial base.

Background Perforated peptic ulcer is one of the common surgical emergencies. Laparoscopic repair has been used to treat perforated peptic ulcers since 1990 and is gaining acceptance. The main concerns are postoperative intra-abdominal collections and performing laparoscopy in the presence of peritonitis. Studies that evaluate the role of laparoscopy in early and delayed presentation are deficient. Aim To compare laparoscopic repair in early versus delayed presentation of perforated peptic ulcer in terms of operative time, conversion rate, postoperative pain, postoperative complications, hospital stay, and conversion rate. Patients and methods This nonrandomized interventional study recruited 140 patients with perforated peptic ulcer who underwent laparoscopic repair and were admitted at the General Surgery Department (Emergency Unit) during the period between May 2019 and June 2021. This study was conducted at the main tertiary referral institution that covers the population in Upper Egypt. Only experienced laparoscopic surgeons participated in this study. Results A total of 140 patients were included in this study; 75 patients underwent laparoscopic repair during the early presentation period (within 24 h), and their mean age was 42 ± 12.4 years, whereas 65 patients underwent laparoscopic repair during the late presentation period (>24 h), and their mean age was 45 ± 9.8 years. Operative time was significantly longer in the late laparoscopic group (120 ± 14.6 min) in comparison with the early group (80 ± 10.6 min). Moreover, the conversion rate was significantly higher in the late group. The postoperative complications were higher in the late group than the early group. Conclusions Laparoscopic repair of perforated peptic ulcer is safe and reliable even in delayed presentations with peritonitis. It has an acceptable morbidity and all the advantages of a minimally invasive surgical approach. [ABSTRACT FROM AUTHOR]

Background: Controversy still exists concerning the optimal reading time of patch testing, and the lack of analysis after day seven might result in missing late positive reactions in rare cases. We aimed to describe our experience with patch test reading and the frequency of early and late positivity, with particular attention to detecting delayed reactions. Material and Methods: This is a retrospective study on 791 patients who were consecutively patch tested with the extended European baseline series and gold salts, between January 2004 and December 2012. Test sites were evaluated on day D2, D3, and D4, and since 2010, on D7 as well, according to the European Society of Contact Dermatitis patch-test guideline. Positivity on D2 or D3 was identified as early reaction, and on D4, D7 and later as late reaction. Results: Of the total 791 patch-tested patients, 773 (97.7%) had at least one positive patch test reaction of which 651 (84.2%) were classified as early (on days 2 or 3), and 122 (15.8%) were classified as late (on day 4 or later). The early and late reaction groups were similar in terms of age, sex and atopy; however, metal hypersensitivity was significantly more frequent in the late reaction group. The substance with the most number of late positive tests was nickel sulfate (16.3%). In terms of relative frequency of positivity on D7 or even later, the most notable substances included neomycin sulfate, gold salts, epoxy resin and polyethylene glycol. Conclusion: The results of our study promote the value of an additional late patch test reading on D4 and D7 or even later in the presence or suspicion of allergy caused by nickel sulfate, cobalt chloride, gold salts, epoxy resin, polyethylene glycol, and neomycin. [ABSTRACT FROM AUTHOR]

We conduct a comprehensive review of embeddedness in entrepreneurship research. Although the term "embeddedness" is frequently used in this field of study, less is known about the ways in which it is operationalized and applied. Using criterion sampling, we analyse 198 articles in order to investigate how embeddedness is conceptualized and what role it plays in the extant entrepreneurship literature. We categorize our findings based on different phases of the entrepreneurial process (early, mature and exit) and outline the dominant focus and the main conceptualization of embeddedness for each phase. We highlight important learnings for each of the three phases and identify potential areas for conceptual development. Across the phases, we find that embeddedness and context are often used interchangeably. We thus call for construct clarity in the field. In the existing literature, entrepreneurs are generally portrayed as reactive to embeddedness, resulting in a loss of entrepreneurial agency. To remedy this, we introduce the term agencement, which takes into account the relationship between the entrepreneurship and embeddedness. Further, entrepreneurs are found to be embedded in multiple contexts at the same time, and embeddedness can be understood at different levels and to different degrees. To address this complexity, it is relevant to focus on the embedding process itself, acknowledging that it takes place in social interactions including cultural, cognitive, and emotional aspects between contexts and across levels. While the extant literature supports the notion that embeddedness is important for understanding entrepreneurship and entrepreneurs, it does not necessarily support our understanding of how embeddedness takes form or why it takes certain forms. We therefore include a call for future research to turn to process and practice theories. [ABSTRACT FROM AUTHOR]

Target Oxbridge is Rare Recruitment’s programme to help students with black African and Caribbean heritage to increase their chances of getting into Cambridge or Oxford Universities. Target Oxbridge and Trinity College, University of Cambridge, launched a unique programme called the Target Oxbridge Year 10 programme to demystify the Universities of Cambridge and Oxford in order to help more 14 and 15 year olds of black heritage prepare to apply to and gain places at these leading universities. This new programme for students in Year 10 featured webinars with Trinity College academics and students, and Target Oxbridge alumni provided advice to Year 10 black British students who are considering attending university. The webinars aimed to demystify Oxford and Cambridge Universities, offer insights into what college life is really like, provide information on the application process, and offer guidance on preparing applications. Students also learned about how degree subject choice can affect their career options. This article provides an evaluation report on the Programme’s effectiveness. [ABSTRACT FROM AUTHOR]

Pre-contact Native American sites in northeastern Colorado typically yield only a few sherds per site (if present), thus little information is known regarding ceramic manufacture by highly mobile groups in this area. Over the past fifty years, systematic archaeological research in Larimer County has generated a large sample of pottery for detailed study. Petrographic analysis of forty samples from ten sites on the low hills of the Front Range indicates a preference for non-local granitic raw materials. Group mobility clearly played a role in where pottery was made (western foothills) as opposed to where it is used (Colorado Piedmont). There are slight differences in paste and temper from the Early Ceramic (AD 150–1150) to the Late Ceramic periods (AD 1540–1860) that could reflect varying approaches to ceramic production as related to preferred source materials. The results suggest the pottery was made on a limited scale and likely for cooking. [ABSTRACT FROM AUTHOR]

Abstract Background Lupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis. Methods The medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality. Results Patients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p

BackgroundTenofovir alafenamide fumarate has been used in late pregnancy; however, no data exist regarding its safety and effectiveness in early and middle pregnancy for mothers with hepatitis B virus infection.AimsTo design a prospective study to investigate the efficacy and safety of TAF in pregnant women with chronic HBV infection during early-middle pregnancy.MethodsPregnant women with active chronic hepatitis B who received tenofovir alafenamide fumarate during early and middle pregnancy were enrolled and followed up until 6 months postpartum. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal hepatitis B virus DNA reduction at delivery and mother-to-child transmission rate.ResultsAmong 98 mothers enrolled, 31 initiated tenofovir alafenamide fumarate in early pregnancy, and 57 in middle pregnancy. The mean (± standard deviation) age was 29.00 (±3.81) years. At delivery, 100% (98/98) of the mothers achieved hepatitis B virus DNA levels

Objective:Non syndromic monogenic obesity is a rare cause of early onset severe obesity in the childhood period. This form may not be distinguishable from other forms of severe obesity without genetic analysis, particularly if patients do not exibit any physical abnormalities or developmental delay. The aim of this study was to screen 41 different obesity-related genes in children with non-syndromic early onset severe obesity.Methods:Children with severe (body mass index-standard deviation score >3) and early onset (

Early extubation after pediatric cardiac surgery has come full circle from being practiced in the early days of pediatric cardiac surgery, falling out of favor with opioid-heavy cardiostable anesthesia, and resurfacing again in more recent times as part of enhanced recovery after surgery practice. Early extubation is variably defined, but is mostly accepted as extubation that occurs within 6-8 h from the end of surgery. In recent years, the debate has shifted from early extubation in the intensive care unit to immediate extubation in the operating theatre. In this review, we examined the benefits and pitfalls of early and immediate extubation, factors that influence the success of early extubation, and potential guidelines for practice and implementation.

Background and Aims: Inflammatory bowel disease (IBD) can lead to long-term complications that significantly impact patients' quality of life and healthcare resource utilization. Prior studies have demonstrated improved short-term outcomes to early exposure of biologics in patients with Crohn's disease (CD) but not in patients with ulcerative colitis (UC). However, there are conflicting data on impact of early intervention on longer-term adverse events. Therefore, we conducted a systematic review and meta-analysis assessing the impact of early biologic treatment on rates of IBD-related surgery., Methods: A systematic search was conducted in April 2022. Studies were included if biologic initiation was compared between patients starting early (<3 years of diagnosis or top-down treatment) vs later (>3 years of diagnosis or step-up treatment). Studies with <1 year of follow-up were excluded. The outcomes were colectomy and CD-related surgery for patients with UC and CD, respectively. Random-effects analyses were conducted to compare rates of IBD surgery between early and late biologic treatment., Results: Eighteen studies were included in the meta-analysis. Three studies included patients with UC and 15 studies included patients with CD. In patients with CD, early biologic therapy was associated with lower odds of surgery (odds ratio, 0.63; 95% confidence interval, 0.48-0.84) compared with late treatment. Conversely, in patients with UC, the odds of colectomy were increased (odds ratio, 2.86; 95% confidence interval, 1.30-6.30)., Conclusions: Early biologic treatment is associated with lower rates of surgery in patients with CD. In contrast, early biologic therapy appears to be associated with higher rates of colectomy in patients with UC, which may be confounded by disease severity., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients., Methods: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes., Results: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection., Conclusions: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of minimally invasive hematoma evacuation with small bone window at different operation time on inflammatory factors, prognosis and serum levels of angiopoietin-1 (Ang-1), endothelin (ET) and vasopressin (AVP) in patients with hypertensive intracerebral hemorrhage (HICH). Methods: From January 2018 to December 2019, 130 patients with HICH in our hospital were selected, and divided into early group (n=64, operation within 6~24 hours after onset) and super early group (n=66, operation within 6 hours after onset) according to different operation time. Perioperative indexes, inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor -α(TNF-α), high sensitivity C-reactive protein (hs-CRP)] levels, prognosis, serum Ang-1, ET, AVP levels, modified Barthel Index (BI), National Institutes of Health Stroke Scale (NIHSS) score, occurrence of complications were compared between the two groups. Results: The hospitalization time of super early group was shorter than that of early group, and intraoperative blood loss was less than that of early group (P<0.05). There was no difference in hematoma clearance rate and operation time between the two groups (P>0.05). 7d after operation, the IL-6, TNF -α, hs-CRP, Ang-1, ET, AVP and NIHSS score of early group and super early group were decreased compared with those before operation, and those of super early group were lower than those of early group (P<0.05). 7 d after operation, the BI score of early group and super early group was increased compared with that before operation, and that of super early group was higher than that of early group (P<0.05). There was no difference in the incidence of complications between the two groups (P>0.05). The survival rate of the super early group was higher than that of the early group (P<0.05). Conclusion: Minimally invasive hematoma evacuation with small bone window within 6 hours after onset of HICH can effectively reduce surgical trauma and improve the ischemic state of brain tissue, promote the recovery of self-help ability and neurological function, reduce the serum inflammatory factors levels, improve the prognosis of patients, improve the quality of life of patients and the security is good. [ABSTRACT FROM AUTHOR]

Background: The effect of early vasopressin initiation on clinical outcomes in patients with septic shock is uncertain. A systematic review and meta-analysis was performed to evaluate the impact of early start of vasopressin support within 6 h after the diagnosis on clinical outcomes in septic shock patients.Methods: We searched the PubMed, Cochrane, and Embase databases for randomized controlled trials (RCTs) and cohort studies from inception to the 1st of February 2021. We included studies involving adult patients (> 16 years)with septic shock. All authors reported our primary outcome of short-term mortality and in the experimental group patients in the studies receiving vasopressin infusion within 6 h after diagnosis of septic shock and in the control group patients in the studies receiving no vasopressin infusion or vasopressin infusion 6 h after diagnosis of septic shock, clearly comparing with clinically relevant secondary outcomes(use of renal replacement therapy(RRT),new onset arrhythmias, ICU length of stay and length of hospitalization). Results were expressed as odds ratio (OR) and mean difference (MD) with accompanying 95% confidence interval (CI).Results: Five studies including 788 patients were included. The primary outcome of this meta-analysis showed that short-term mortality between the two groups was no difference (odds ratio [OR] = 1.09; 95% CI, 0.8 to 1.48; P = 0.6; χ2 = 0.83; I2 = 0%). Secondary outcomes demonstrated that the use of RRT was less in the experimental group than that of the control group (OR = 0.63; 95% CI, 0.44 to 0.88; P = 0.007; χ2 = 3.15; I2 = 36%).The new onset arrhythmias between the two groups was no statistically significant difference (OR = 0.59; 95% CI, 0.31 to 1.1; P = 0.10; χ2 = 4.7; I2 = 36%). There was no statistically significant difference in the ICU length of stay(mean difference = 0.16; 95% CI, - 0.91 to 1.22; P = 0.77; χ2 = 6.08; I2 = 34%) and length of hospitalization (mean difference = -2.41; 95% CI, -6.61 to 1.78; P = 0.26; χ2 = 8.57; I2 = 53%) between the two groups.Conclusions: Early initiation of vasopressin in patients within 6 h of septic shock onset was not associated with decreased short-term mortality, new onset arrhythmias, shorter ICU length of stay and length of hospitalization, but can reduce the use of RRT. Further large-scale RCTs are still needed to evaluate the benefit of starting vasopressin in the early phase of septic shock. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Arabian Sciences Heritage is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In early January 2020, Thailand became the first country where a coronavirus disease 2019 (COVID‐19) patient was identified outside China. In this study, 23 whole genomes of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) from patients who were hospitalized from January to March 2020 were analyzed, along with their travel histories. Six lineages were identified including A, A.6, B, B.1, B.1.8, and B.58, among which lineage A.6 was dominant. Seven patients were from China who traveled to Thailand in January and early February. Five of them were infected with the B lineage virus, and the other two cases were infected with different lineages including A and A.6. These findings present clear evidence of the early introduction of diverse SARS‐CoV‐2 clades in Thailand. [ABSTRACT FROM AUTHOR]

The study's aim was to examine the effect of chronotype on cognitive performance during a single night shift. Data were collected from 72 (36f) young, healthy adults in a laboratory study. Participants had a 9 h sleep period (03:00-12:00) followed by an 8 h night shift (23:00-07:00). During the night shift, participants completed five test sessions, which included measures of subjective sleepiness, subjective alertness, and sustained attention (i.e., psychomotor vigilance task; PVT). Dim light melatonin onset (DLMO) was derived from saliva samples taken during the evening preceding the night shift. A tertile split of DLMO was used to determine three chronotype categories: earlier (DLMO = 20:22 ± 0:42), intermediate (DLMO = 21:31 ± 0:13), and later (DLMO = 22:54 ± 0:54). There were (a) significant main effects of test session (all p < 0.001); (b) no main effects of chronotype; and (c) no interaction effects between chronotype and test session on sleepiness, alertness, PVT response time, and PVT lapses. The results indicate that under controlled sleeping conditions, chronotype based on dim light melatonin onset did not affect nighttime performance. Differences in performance during night shift between chronotypes reported by field studies may be related to differences in the amount and/or timing of sleep before or between night shifts, rather than circadian timing. [ABSTRACT FROM AUTHOR]

Prion diseases are rapidly progressive fatal conditions caused by abnormally shaped proteins. Sporadic Creutzfeldt - Jakob disease (sCJD) is the most common human prion disorder accounting for 85–90 % of cases. Clinical manifestations include rapidly evolving dementia in conjunction with neurological symptoms such as ataxia, myoclonus, pyramidal and extrapyramidal signs. However, the early symptoms of the disease are often non-specific and mental disorder is delayed, making the diagnostic process difficult and challenging. We present 3 cases with atypical early symptoms and late onset of cognitive decline. The first case presented with isolated visual symptoms (Heidenhain variant), the second patient had isolated anomic aphasia and the third one non-convulsive status epilepticus. A review of the past literature concerning the atypical and rare early clinical features of the sCJD was conducted. The following manifestations were found: psychiatric and visual symptoms, which are relatively common, epileptic seizures, otologic symptoms and presentation of sCJD as an acute vascular event. Moreover, language, communication and writing impairments, movement disorders, symptoms from the peripheral nervous system and bulbar signs were reported as well. Increased clinical suspicion, along with the aid of existing diagnostic methods and the development of novel techniques could contribute to a better understanding of the disease's pathophysiology, early and accurate diagnosis and improvement of patient management. [ABSTRACT FROM AUTHOR]

Background: The increased prevalence of atopic dermatitis (AD) in dogs necessitates research in its disease etiology. Objectives: To explore the association between puppyhood dietary exposures and prevalence of owner‐reported allergy/atopy skin signs (AASS) after the age of 1 year. Animals: Four thousand and twenty‐two dogs were eligible, 1158 cases, and 2864 controls. Methods: This cross‐sectional hypothesis‐driven observational study was extracted from the DogRisk food frequency questionnaire. Forty‐six food items and the ratio of 4 major diet types were tested for their association with AASS incidence later in life. Potential puppyhood dietary risk factors for AASS incidence were specified using binary multivariable logistic regression. The model was adjusted for age and sex. Results: Eating raw tripe (odds ratio, 95% confidence intervals OR, 95% CI = 0.36, 0.16‐0.79; P =.01), raw organ meats (OR, 95% CI = 0.23, 0.08‐0.67; P =.007), human meal leftovers, and fish oil supplements as well as eating more that 20% of the diet as raw and/or <80% of the diet as dry, in general, were associated with significantly lower AASS incidence in adulthood. In contrast, dogs fed fruits (OR, 95% CI = 2.01, 1.31‐3.07; P =.001), mixed‐oil supplements, dried animal parts, and dogs that drank from puddles showed significantly higher AASS incidence in adulthood. Conclusions and Clinical Importance: Puppyhood exposure to raw animal‐based foods might have a protective influence on AASS incidence in adulthood, while puppyhood exposure to mixed oils, heat processed foods and sugary fruits might be a potential risk factor of AASS incidence later. The study suggests a causal relationship but does not prove it. [ABSTRACT FROM AUTHOR]

Introduction: To determine which day automated refraction stabilised the first week after uneventful cataract surgery. Methods: This was a prospective, single-blinded, randomised cohort study of 148 eyes in 148 consecutive patients undergoing uneventful cataract surgery. Automated refraction was measured from days 2 to 7 after surgery and compared to automated refraction measured 6 weeks post-surgery. We compared measurements using a hierarchical mixed-effect model. Results: Our adjusted results did not show a statistically significant change in spherical equivalent between the first week after surgery and 6 weeks after surgery (p-values: day 2: 0.914, day 3: 0.922, day 4: 0.168, day 5: 0.211, day 6: 0.457, day 7: 0.621). We measured the spherical error as stable except for day 5, where a statistically significant change of 0.32 dioptre (p = 0.049) was detected. Similarly, the cylindrical error was also stable on all days of measurements except on day 6, where a significant change of 0.28 dioptre (p = 0.034) was detected. Conclusion: The adjusted spherical equivalent was stable on days 2–7 after uneventful cataract surgery in our study population. However, as we observed a statistically significant difference in spherical and cylindrical errors on days 5 and 6, respectively, we could not conclude that automated refraction stabilised the first week after uncomplicated cataract surgery. [ABSTRACT FROM AUTHOR]

PURPOSE OF THE STUDY The aim of this study is to show new possibilities for the treatment of anterior cruciate ligament injuries. For many years, the long-established rules have been followed. However, throughout history, treatment strategies have been gradually modified. The advent of new modern technologies now makes it possible to perform reconstructive procedures already in the acute phase, and thus shorten the treatment time significantly. MATERIAL AND METHODS 85 patients were followed after an acute knee injury with an isolated anterior cruciate ligament (ACL) lesion. There were 51 men and 34 women with the average age of 32 years. All patients underwent an acute knee arthroscopy with subsequent ACL reconstruction according to the type of lesion. The results were evaluated according to the clinical examination, Lysholm and Tegner activity scores. We compared 2 surgical techniques (Internal Brace, All-Inside ACL reconstruction) and assessed the possible occurrence of complications. RESULTS The injury was most often observed in patients aged 20–40 years, when mainly sports activities put a major strain on the knee joint. After performing ACL reconstruction, all patients reported a subjective improvement in the overall condition. The number of complications was very low – only in connection with a slower warm-up of the knee joint after surgery. DISCUSSION All patients achieved full stabilization of the knee joint, which is objectified by an increase in the Lysholm score. The improvement in patient’s subjective feelings is also confirmed by the increase in Tegner activity scores. Only a few patients experienced a slight restriction of movement in the 8th week after surgery, but thanks to intensive rehabilitation the function of the knee joint was completely restored within 3 months of the operation. CONCLUSIONS Our study proves that if the set rules are followed, it is possible to perform the ACL reconstruction already in the acute phase. However, in order to choose this approach, the patient's motivation, gently performed procedure and early intensive rehabilitation are necessary. When meeting these criteria, the patient is able to return to normal life, including sports activities, quite early and there is no increased risk of complications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate long-term disease-specific survival (DSS) and organ preservation (OP) rates in patients affected by Tis-T2 glottic squamous cell carcinoma (SCC) treated by carbon dioxide transoral laser microsurgery (CO2 TOLMS). Study Design: Single-center retrospective cohort study. Setting: Tertiary academic hospital. Methods: The study included patients treated by CO2 TOLMS for Tis-T2 glottic SCC at the Department of Otorhinolaryngology–Head and Neck Surgery of the University of Brescia, Italy, from 1988 to 2018. The male:female ratio was 11.2:1, and the mean age was 64 years (range, 31-95). T categories were distributed as follows: 124 (10%) Tis, 646 (54%) T1a, 172 (15%) T1b, and 246 (21%) T2. Results: Ten- and 20-year DSS rates were 97.6% and 96.3%, respectively, and 10- and 20-year OP rates were 94.7% and 93%. During the follow-up, 91% of patients were treated by CO2 TOLMS alone, while the remaining needed adjunctive treatments. Assessing the impact of multiple sessions of CO2 TOLMS, DSS showed no significant difference in terms of patients treated by 1, 2, or >2 procedures. Conversely, patients treated by >2 sessions of CO2 TOLMS showed a significantly worse OP rate. Conclusions: Our series validates CO2 TOLMS as a long-term treatment strategy for early glottic SCC. Salvage CO2 TOLMS provided optimal results in terms of DSS and OP in patients with recurrence after previous transoral surgery. [ABSTRACT FROM AUTHOR]

ObjectiveWe prospectively examined evidence for the sustained effects of early intervention based on a follow-up study of 39 children with ASD who began participation in a randomized clinical trial testing the effectiveness of the Early Start Denver Model (ESDM) at age 18 to 30 months. The intervention, conducted at a high level of intensity in-home for 2 years, showed evidence of efficacy immediately posttreatment.MethodThis group of children was assessed at age 6 years, 2 years after the intervention ended, across multiple domains of functioning by clinicians naive to previous intervention group status.ResultsThe ESDM group, on average, maintained gains made in early intervention during the 2-year follow-up period in overall intellectual ability, adaptive behavior, symptom severity, and challenging behavior. No group differences in core autism symptoms were found immediately posttreatment; however, 2 years later, the ESDM group demonstrated improved core autism symptoms and adaptive behavior as compared with the community-intervention-as-usual (COM) group. The 2 groups were not significantly different in terms of intellectual functioning at age 6 years. Both groups received equivalent intervention hours during the original study, but the ESDM group received fewer hours during the follow-up period.ConclusionThese results provide evidence that gains from early intensive intervention are maintained 2 years later. Notably, core autism symptoms improved in the ESDM group over the follow-up period relative to the COM group. This improvement occurred at the same time that the ESDM group received significantly fewer services. This is the first study to examine the role of early ESDM behavioral intervention initiated at less than 30 months of age in altering the longer-term developmental course of autism.

Introduction: Hip spica with or without prior traction has become a standard treatment for closed isolated femoral shaft fracture in children below six years. The time of hip spica application is not uniform in the existing literature. The aim of this study is to find out the prevalence of complication of early application of one and a half hip spica for femoral shaft fractures in children below six years in a tertiary care hospital. Methods: A descriptive cross-sectional study was done among 42 children who were managed with early hip spica application (within 72 hours) for femoral shaft fracture from January 2015 to December 2020 after receiving ethical clearance from Institutional Review Committee. Convenient sampling technique was done. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. Results: Complication was seen in nine (21.4%) (95% Confidence Interval= 9.02-33.84) patients. Skin breakdown from local pressure had the highest prevalence in our study which was documented in three (7.14%) patients who resolved with conservative treatment. Conclusions: The prevalence of complication of early application of one and a half hip spica for femoral shaft fractures in children below six years was similar to other studies done in similar setting.

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown.Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI.Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56–73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P < 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472–35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125–22.388) compared to patients with early CI but no recurrence.Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.

Background: Effectiveness of early intensive aphasia rehabilitation after stroke is unknown. The Very Early Rehabilitation for SpEech trial (VERSE) aimed to determine whether intensive aphasia therapy, beginning within 14 days after stroke, improved communication recovery compared to usual care. Methods: Prospective, randomized, single-blinded trial conducted at 17 acute-care hospitals across Australia/New Zealand from 2014 to 2018. Participants with aphasia following acute stroke were randomized to receive usual care (direct usual care aphasia therapy), or one of two higher intensity regimens (20 sessions of either non-prescribed (usual care-plus or prescribed (VERSE) direct aphasia therapy). The primary outcome was improvement of communication on the Western Aphasia Battery-Revised Aphasia Quotient (AQ) at 12 weeks after stroke. Our pre-planned intention to treat analysis combined high intensity groups for the primary outcome. Findings: Among 13,654 acute stroke patients screened, 25% (3477) had aphasia, of whom 25% (866) were eligible and 246 randomized to usual care (n = 81; 33%), usual care-plus (n = 82; 33%) or VERSE (n = 83; 34%). At 12 weeks after stroke, the primary outcome was assessed in 217 participants (88%); 14 had died, 9 had withdrawn, and 6 were too unwell for assessment. Communication recovery was 50.3% (95% CI 45.7–54.8) in the high intensity group (n = 147) and 52.1% (95% CI 46.1–58.1) in the usual care group (n = 70; difference −1.8, 95% CI −8.7–5.0). There was no difference between groups in non-fatal or fatal adverse events (p = 0.72). Interpretation: Early, intensive aphasia therapy did not improve communication recovery within 12 weeks post stroke compared to usual care. [ABSTRACT FROM AUTHOR]

Copyright of Revista Biológico Agropecuaria Tuxpan is the property of Revista Biologico Agropecuaria Tuxpan and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The ideal timing and technique of tracheostomy vary among patients and may impact outcomes. We aim to examine the association between tracheostomy timing, placement technique, and patient demographics on survival. Study Design: Retrospective cohort study. Methods: A retrospective review was performed for all patients who underwent tracheostomy in 2016 and 2017 at one urban academic tertiary‐care hospital. Kaplan–Meier curves were created based on combinations of tracheostomy timing and technique (early percutaneous, early non‐percutaneous, late percutaneous, and late non‐percutaneous). Cox proportional hazard models were used to determine multivariable effects of timing, technique, and other demographic factors. Primary outcome measures were tracheostomy‐related mortality and overall survival. Secondary outcomes were in‐hospital, 30‐day, and 90‐day mortality. Results: Our study included 523 patients. There were six tracheostomy‐related deaths, with hemorrhage and tracheoesophageal fistula being the most common causes. Tracheostomy timing and technique combinations were not associated with differences in all‐cause mortality or survival following discharge. Cox proportional hazard models showed that Charlson Comorbidity Index (CCI) and unknown partner status were associated with a decrease in survival (P <.01 and P =.05, respectively). Additionally, patient age, gender, race, CCI, and body mass index were not independently associated with changes in survival. Conclusion: Late and non‐percutaneous tracheostomies were associated with more tracheostomy‐related deaths, but timing and technique were not associated with differences in patient survival. Multiple regression analysis showed that increased patient comorbidities, measured via CCI, and unknown partner status were independently associated with decreased survival. Proceduralists should discuss timing, technique, and patient social factors together with the medical care team when constructing plans for postdischarge management. Level of Evidence: 4 Laryngoscope, 131:1468–1473, 2021 [ABSTRACT FROM AUTHOR]

Chronotype reflects circadian timing and can be determined from biological markers (e.g., dim light melatonin onset; DLMO), or questionnaires (e.g., Morningness-Eveningness Questionnaire; MEQ, or Munich Chronotype Questionnaire; MCTQ). The study's aim was to quantify concordance between chronotype categorisations based on these measures. A total of 72 (36f) young, healthy adults completed the MEQ and MCTQ and provided saliva samples hourly in dim light during the evening in a laboratory. The corrected midpoint of sleep on free days (MSFsc) was derived from MCTQ, and tertile splits were used to define early, intermediate and late DLMO-CT, MEQ-CT and MSFsc-CT chronotype categories. DLMO correlated with MEQ score (r = -0.25, p = 0.035) and MSFsc (r = 0.32, p = 0.015). For early, intermediate and late DLMO-CT categories, mean(SD) DLMO were 20:25(0:46), 21:33(0:10) and 23:03(0:53). For early, intermediate and late MEQ-CT categories, mean(SD) MEQ scores were 60.5(5.3), 51.4(2.9) and 40.8 (5.0). For early, intermediate and late MSFsc-CT categories, mean(SD) MSFsc were 03:23(0:34), 04:37(0:12) and 05:55(0:48). Low concordance of categorisations between DLMO-CT and MEQ-CT (37%), and between DLMO-CT and MSFsc-CT (37%), suggests chronotype categorisations depend on the measure used. To enable valid comparisons with previous results and reduce the likelihood of misleading conclusions, researchers should select measures and statistical techniques appropriate to the construct of interest and research question. [ABSTRACT FROM AUTHOR]

• The negative converting ratio was 16.4% and 41.0% on days 7 and 14, respectively. • 34.1% and 60.3% of subjects had least one negative RT-PCR result on days 7 and 14. • Joint testing represents an effective means of minimizing the misdiagnosis. The real-time polymerase chain reaction (RT-PCR) test is recommended for the diagnosis of COVID-19 and provides a powerful tool to identify new infections and facilitate contact tracing. In fact, as the prevalence of COVID-19 decreases, this RT-PCR testing remains as the main preventive measure to avoid rebound. However, inconsistent results can lead to misdiagnoses in the clinic. These inconsistencies are due to the variability in (1) the collection times of biological samples post infection, and (2) sampling procedures. We applied the Kaplan–Meier method and multivariate logistic regression on RT-PCR results from 258 confirmed patients with COVID-19 to evaluate the factors associated with negative conversion. We also estimated the proportion (%) of negative conversion among patients who had tested twice or more, and compared the proportions arising from oropharyngeal swabs, sputum, and combined double testing, respectively. The proportion of negative conversion was 6.7% on day 4, 16.4% on day 7, 41.0% at 2 weeks, and 61.0% at 3 weeks post-admission. We also found that 34.1% and 60.3% of subjects had at least one negative RT-PCR result on days 7 and 14 after the onset of symptoms, respectively. The proportion of negative conversions following sputum testing was higher than that from oropharyngeal swabs in the early stages but this declined after the onset of symptoms. In the absence of effective treatments or vaccines, efficient testing strategies are critical if we are to control the COVID-19 epidemic. According to this study, early, consecutive and combined double testing, will be the key to identify infected patients, particularly for asymptomatic and mild symptomatic cases. These strategies will minimize misdiagnosis and the ineffective isolation of infected patients. [ABSTRACT FROM AUTHOR]

Objective: Previous systematic reviews looking at timing of anterior cruciate ligament reconstruction (ACLR) examined the functional outcomes and range ofmotion; however, few have quantified the effect of timing of surgery on secondary pathology. The goal of this study was to analyze the effects of early ACLRs versus delayed ACLR on the incidence ofmeniscal and chondral lesions. Data Sources: We searched MEDLINE, EMBASE, and CINAHL on March 20, 2018, for randomized control trials (RCTs) that compared early and delayed ACLR in a skeletally mature population. Two reviewers independently identified trials, extracted trial-level data, performed risk-of-bias assessments using the Cochrane Risk of Bias tool, and evaluated the study methodology using the Detsky scale. A meta-analysis was performed using a random-effectsmodelwith the primary outcome being the total number of meniscal and chondral lesions per group. Results: Of 1887 citations identified from electronic and hand searches, we included 4 unique RCTs (303 patients).We considered early reconstruction as,3 weeks and delayed reconstruction as.4 weeks after injury. There was no evidence of a difference between early and late ACLR regarding the incidence of meniscal [relative risk (RR), 0.98; 95% confidence interval (CI), 0.74-1.29] or chondral lesions (RR, 0.88; 95% CI, 0.59-1.29), postoperative infection, graft rupture, functional outcomes, or range of motion. Conclusions: We found no evidence of benefit of early ACLR. Further studies may consider delaying surgery even further (eg, .3 months) to determine whether there are any real benefits to earlier reconstruction. [ABSTRACT FROM AUTHOR]

Recent evidence linked early menarche to a higher risk of insulin-resistance (IR) and nonalcoholic fatty liver disease (NAFLD) in adulthood. We aimed to evaluate the impact of early menarche on glucose derangements and NAFLD in a sample of Italian adolescents with obesity. Anthropometric and biochemical evaluations were conducted in all the enrolled 318 obese patients (mean age 12.31 ± 2.95 years). NAFLD was defined by the presence of ultrasound detected liver steatosis and/or alanine transaminase (ALT) levels >40 IU/L. Patients with early menarche showed both higher homeostasis model assessment of insulin-resistance (HOMA-IR) (p=0.008) and ALT (p=0.02) values, an increased prevalence of NAFLD (p=0.001), and lower Matsuda and Insulinogenic Index (IGI) values than the other obese patients. The association between early menarche and both ALT and Matsuda Index remained significant in General Linear Models (GLMs) in which respectively body mass index standard deviation score (BMI-SDS) and Matsuda Index, and BMI-SDS were included as covariates. Patients with early menarche also showed a higher risk of both HOMA-IR>3 (OR 1.69, CI 1.05–2.70, p=0.02) and NAFLD (OR 1.10, CI 1.01–1.21, p=0.03). Girls with obesity presenting early menarche showed higher HOMA-IR levels, lower Matsuda Index and IGI values, and higher risk of NAFLD compared to girls without early menarche. [ABSTRACT FROM AUTHOR]

A life-threatening complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is acute respiratory distress syndrome. Our understanding of the pathologic changes in coronavirus disease 2019 (COVID-19) is based almost exclusively on post-mortem analyses of adults. These studies established several hallmarks of SARS-CoV-2 lung infection, including diffuse alveolar damage, microvascular thrombi, and acute bronchopneumonia. We describe a fatal example of COVID pneumonia in a 9-year-old girl who presented with fever 10 months following the diagnosis of ALK-positive anaplastic large cell lymphoma (ALCL). A chest computed tomography scan revealed left upper lobe lung consolidation and nodular airspace disease, and an initial SARS-CoV-2 nasopharyngeal swab (RT-PCR) was negative. A subsequent lung biopsy performed due to concern for relapsed ALCL demonstrated sheets of intra-alveolar and interstitial macrophages, and macrophage-rich fibrinous exudates. Immunohistochemical and in-situ hybridization stains confirmed these macrophages as the predominant SARS-CoV-2-infected cell type. Subsequent RT-PCR testing of upper and lower respiratory tract samples was positive for SARS-CoV-2 infection. Whole genome sequencing confirmed the presence of the B.1.617.2 (Delta) variant. This biopsy illustrates the histopathologic features of early COVID pneumonia in antemortem lung tissue from a pediatric patient, and establishes macrophages as a potential source of SARS-CoV-2 amplification. [ABSTRACT FROM AUTHOR]