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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.

Tracheostomy is a surgical procedure that frequently performed for patients in the intensive care units (ICUs). Prolonged mechanical ventilation (MV) is the main indication for tracheostomy in the ICU.This study aimed to compare the effect of early versus late tracheostomy on duration of mechanical ventilation and ICU length of stay in traumatic brain injury patients and to determine the appropriate timing to perform tracheostomy for those patients.A Prospective comparative study was performed for head trauma patients with Glasgow coma scale (GCS) less than eight who needed endotracheal intubation with or without mechanical ventilation in the ICU of Al-Sadr Teaching Hospital in Basrah from February 2019 up to December 2019.In this study, there were 94% males and 6% females, 52% were in the age group between 20-40 years, median duration on endotracheal tube in early tracheostomy (ET) group was 5 days while in late tracheostomy (LT) group was 11 days. Total duration on MV was significantly shorter in ET group (9.63±1.87 versus 17.81±6.66 days in LT group; p

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.

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 (COSingle-center retrospective cohort study.Tertiary academic hospital.The study included patients treated by COTen- 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 COOur series validates CO

ackground: Human epidermal growth factor receptor 2 (HER2) plays an important role in the development and progression of breast cancer. To understand the precise association, this meta-analysis was conducted to estimate the association between HER2Ile655Val single nucleotide polymorphism (SNP) and susceptibility to early-onset breast cancer. Methods A comprehensive database retrieval from PubMed, Embase, Web of Science and Google Scholar was pooled to investigate links between the HER2Ile655Val SNP and risk of breast cancer. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to appraise the association under the additive model (Ile vs. Val), dominant model (Val/Val + Ile/Val vs. Ile/Ile), and recessive model (Val/Val vs. Ile/Val + Ile/Ile). Results Seventeen relevant studies with 11,749 cases and 8,105 controls were finally included. We found that HER2Ile655Val SNP is associated with an increased risk of breast cancer in an additive and dominant model. In the subgroup analysis with age stratification, a significant association between the HER2 codon 655 SNP and the risk of breast cancer was found in young women in an additive, dominant, and recessive model; conversely, no significant associations were indicated in older women. In the breast cancer subgroup, HER2Ile655Val SNP was significantly associated with younger age women with breast cancer in the dominant model. In contrast, no association between the HER2 codon 655 SNP and age was found in control populations. Conclusion Our findings suggest that the Val allele in HER2 codon 655 SNP is strongly associated with breast cancer susceptibility in the young female population and is also significantly associated with younger age in women with breast cancer. HER2Ile655Val SNP might be a susceptibility factor that favours early-onset breast cancer. .

Introduction Since most hip fractures are treated surgically, it is imperative to find an optimum fracture-to-surgery time to decrease the potential complications and enhance postoperative outcomes. In comparison to the vast plethora of literature available on surgical delay and its implications on mortality, very little, if any, research is available on the impact of delayed surgery on postoperative ICU admission. The primary objective of our study is to examine the factors influencing post-surgical ICU admission in order to work on preventive strategies to reduce the potential associated morbidity. Material and methods Investigators did a nested case control study in a university hospital. A case was defined as a patient who had postoperative ICU admission while controls were patients who did not have postoperative ICU admission after hip fracture surgery. The primary outcome variable was postoperative ICU admission. The exposure variable was defined as the time to surgery which was categorized into two categories; early and late; the early surgery included patients who were operated within ≤ 48 h and the late included patients who had their surgery >48 h. Information on potential confounders including age, type of the procedure and comorbidities were also obtained. Result reported in-line with STROCSS criteria. Results A total cohort of 1084 hip fracture surgeries were performed from January 2010 to December 2018. After screening for eligibility criteria, 911 patients were eligible for the final simple logistic regression analysis (48 cases and 863 controls). Our exposure variable i.e. time from admission to surgery showed no difference between cases and controls. The odds of being treated with Hemiarthroplasty among cases admitted in ICU was 2.42 times as compared to controls (aOR = 2.42; 95% C.I. 1.21–4.86). Conclusion Our study did not find an association between surgical delay and post-operative ICU admission after accounting for other covariates and potential confounders., Highlights • There is a controversy of the benefits of early hip fracture surgery. • Delay in surgery is postulated to carry higher risk of postoperative ICU admission. • However, this higher risk was statistically insignificant in the current study.

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.

On an acute urological ward, it is challenging to meet all needs of patients with life-limiting progressive cancer disease in complex situations. The focus shifts from curation to the holistic palliative approach aiming at patients' and their families' needs and planning care in advance with an interprofessional attitude. Based on a patient with castration refractory prostate carcinoma with multiple metastasis, the aim of this case study is to describe the palliative care approach, using the established so-called SENS-structure (Symptoms, End-of-life decisions, Network and Support of the carer) in which the bio-, psycho-, social and spiritual needs are addressed. We report on our practice experience using the SENS-structure, in which the team discusses palliative care interventions with patients and their family: management of (potential) symptoms and self-supporting strategies, expectations and end-of-life decisions including advance care planning, evaluation of patients' social and professional network and setting up additional support. The palliative care team provides advice to the treating team on future treatment strategies and care activities. The complex situation of a patient with metastatic prostate cancer and his personal sufferings illustrate the interprofessional use and person-centred focus of the SENS-structure. Important in this phase is-next to the family carers-the involvement of all professions and disciplines to break down the complexity of the situation into manageable proportions. Early involvement of palliative care for patients with advanced cancer is highly recommended. The SENS-structure helps to prioritize and include the personalized approach which is strongly supported by nurses.

Introduction Roughly one third of new non-small cell lung cancer (NSCLC) is diagnosed at early stages. While lobectomy can improve mortality in this group, about 30-55% of patients will experience disease recurrence. Increased investigation into the factors affecting recurrence, particularly tumor molecular genetics such as EGFR mutations, is needed. Materials and methods We conducted a single-center retrospective study of 282 patients with early or locally advanced lung adenocarcinoma, with or without EGFR mutations, who underwent definitive therapy. We then assessed recurrence, stage at recurrence, time to recurrence and progression-free survival (PFS). Results We identified 142 patients with EGFR-mutated and 140 EGFR-wildtype lung adenocarcinoma. Overall progression between groups was equivalent at ~40% at 5 years; no difference in PFS was observed at any time-point. However, among those who recurred, EGFR-mutated lung cancer had increased rates of metastatic recurrence compared to EGFR-wildtype disease (97% vs 68%, p = 0.007). Conclusions EGFR-mutated disease may be associated with a higher risk of metastatic recurrence. Molecular testing may be a promising tool for risk stratification and surveillance following definitive management for early stage disease. Future prospective, multi-center cohort studies are needed to confirm these findings and improve our understanding of how EGFR mutation contributes to prognosis and clinical outcomes.

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity.

INTRODUCTION[|]Nowadays early rehabilitation studies in stroke patients have gained momentum. Although early rehabilitation is reported to be more effective, what is really meant of the term 'early' is not clear. The term early can sometimes refer to minutes, sometimes to hours, while sometimes even to days. The aim of the present study was to determine whether the initiation time of rehabilitation has an effect on impairment, trunk function and degree of recovery in ischemic stroke patients.[¤]METHODS[|]Twenty-one patients with acute ischemic stroke diagnosis who were admitted to the hospital were included in the study. The rehabilitation was initiated as early as possible and the elapsed time; from the stroke occurrence to initiation of rehabilitation, was noted. Glasgow Outcome Scale, National Institutes of Health Stroke Scale and Trunk Impairment Scale were used to measure the effect of treatment. Evaluations were made at baseline and at discharge.[¤]RESULTS[|]All of the patients were discharged and no complication aroused in any patient. The elapsed time; from the stroke occurrence to initiation of rehabilitation was 12 hours in the earliest patient and 234 hours at the latest (median (IQR): 79.5 (58,5/107,5). When the results were examined, no statistically significant relationship was present in between the initiation time of rehabilitation on impairment, trunk function and on degree of recovery (p> 0,05).[¤]DISCUSSION AND CONCLUSION[|]The results of this study showed that time of initiation of rehabilitation does not have a direct effect on recovery. Ischemic stroke patients included in the early rehabilitation program have shown improvements when compared to baseline. However, controlled studies are needed to determine the extent to which early rehabilitation contributes to recovery.[¤]

Early hypertransaminasemia after kidney transplantation (KT) is frequent. It has been associated with the crosstalk produced between the liver and the kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We present a retrospective study analyzing the increase in serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) during the first three months post-KT in 151 recipients who received thymoglobulin as induction therapy, either from brain-death donors (DBD, n = 75), controlled circulatory death donors (cDCD, n = 33), or uncontrolled DCD (uDCD, n = 43). Eighty-five KT recipients from DBD who received basiliximab were included as controls. From KT recipients who received thymoglobulin, 33.6/43.4% presented with an increase in AST/ALT at 72 h post-KT, respectively. Regarding donor type, the percentage of recipients who experienced 72 h post-KT hypertransaminasemia was higher in uDCD group (65.1/83.7% vs. 20.3/26% in DBD and 20.7/27.6% in cDCD, p &lt, 0.001). Within the control group, 9.4/12.9% of patients presented with AST/ALT elevation. One month after transplant, AST/ALT values returned to baseline in all groups. The multivariate analysis showed that uDCD recipients had 6- to 12-fold higher risk of developing early post-KT hypertransaminasemia. Early post-KT hypertransaminasemia is a frequent and transient event related to the kidney donor type, being more frequent in uDCD recipients.

Introductions Results with convalescent plasma therapy in coronavirus disease 2019 (COVID-19) have been contradictory. Timing seems to be an important factor for COVID-19 convalescent plasma(CCP) to be effective. Aim of this study is to compare disease outcomes in hospitalized COVID-19 patients who were treated with CCP within first three or seven days of symptoms to patients with symptoms longer than seven days. Material and methods A multicenter retrospective study was conducted to evaluate disease outcomes in hospitalized COVID-19 patients who received CCP in addition to standard of care (SOC) approach. Patients were subgrouped according to time of CCP administration; within three days of symptoms, seven days of symptoms and after seven days of symptoms. A control group was formed from age, gender and comorbidity matched hospitalized patients who received SOC treatments without CCP. Length of hospital stay, rates of anti-inflammatory treatment initiation, intensive care unit (ICU) admission and mortality was set as outcome measures. Results A total of 223 patients were enrolled in this study, 113 patients received CCP (38 within three days, 63 within seven days, 50 after seven days of symptom onset). Rate of anti-inflammatory treatment initiation was significantly lower (38.1 % vs 62.7 %, p = 0.002, relative risk, 0.60,73; 95 % confidence interval [CI], 0.42 to 0.85) and length of hospital stay was significantly shorter (median(IQR) 8(4) days vs 9.5(5.25) days, p = 0.0025) in patients who received CCP within seven days of symptom onset when compared to SOC group. Conclusion CCP therapy may provide better outcomes when applied within seven days of symptoms.

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.

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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00372-z.

Background: Diabetic ketoacidosis (DKA) is one of the most serious complications after diabetes poor control, which seriously threatens human life, health, and safety. DKA can rapidly develop within hours or days leading to death. Early evaluation of the prognosis of DKA patients and timely and effective intervention are very important to improve the prognosis of patients. The combination of several variables or characteristics is used to predict the poor prognosis of DKA, which can allocate resources reasonably, which is beneficial to the early classification intervention and clinical treatment of the patients. Methods: For the acquisition of required data of eligible prospective/retrospective cohort study or randomized controlled trials (RCTs), we will search for publications from PubMed, Web of science, EMBASE, Cochrane Library, Google scholar, China national knowledge infrastructure (CNKI), Wanfang and China Science and Technology Journal Database (VIP). Two independent reviewers will read the full English text of the articles, screened and selected carefully, removing duplication. Then we evaluate the quality and analyses data by Review Manager (V.5.4). Results data will be pooled and meta-analysis will be conducted if there's 2 eligible studies considered. Results: This systematic review and meta-analysis will evaluate the value of the prediction models for the prognosis of DKA in the emergency department. Conclusions: This systematic review and meta-analysis will provide clinical basis for predicting the prognosis of DKA. It helps us to understand the value of predictive models in evaluating the early prognosis of DKA. The conclusions drawn from this study may be beneficial to patients, clinicians, and health-related policy makers. Study registration number: INPLASY202150023.

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.

Retinal folds are rare complications of rhegmatogenous retinal detachment surgery. They may be located in periphery or involve macula, with the latter ones being associated with severe visual loss. Due to the paucity of scientific reports, its management remains debatable. Most authors advocate an early surgical intervention for symptomatic macular folds (MF). We present 2 cases of symptomatic dry macular fold which were managed successfully after different time intervals. As evidence gets collected that late intervention also leads to good visual outcome, long standing MF should not be considered an absolute contraindication for surgical intervention.

Introduction and aims Pretransplant administration of cyclosporine (CsA) may reduce post-transplant maintenance dose and consequently CsA inhibitor nephrotoxicity and helps in achieving the desired target C2 levels earlier. The optimum dose or timing of administration of CsA induction dose is still debatable. Patients and methods We compared three different protocols for pretransplant administration of CsA aiming to reach a target C2 therapeutic level of greater than 800 ng/ml on the third day post-transplant. Sixty kidney transplant recipients from Cairo University hospitals were divided into: group 1 (n=20) who received a single CsA induction dose of 2 mg/kg 12 h pretransplant; group 2 (n=20) who received four CsA consecutive doses of 4 mg/kg 48 h pre-transplant; and group 3 (n=20) who received four CsA consecutive doses of 2 mg/kg 48 h pretransplant. Results The desired therapeutic level in the earlier post-transplantation period was achieved in 65% in group 1, 100% in groups 2 and 3). In group 2 a lower dose was needed to maintain C2 within the therapeutic range during the first year post-transplantation (P

This prospective, three-center, randomized study assessed the efficacy and safety of early vitamin A supplementation in improving the outcomes of retinopathy of prematurity in extremely preterm infants. Two hundred sixty-two extremely preterm infants were randomized to vitamin A and control groups. Vitamin A supplementation reduced its deficiency in these infants., Purpose: This study assessed the efficacy and safety of early vitamin A (VA) supplementation to improve outcomes of retinopathy of prematurity in extremely preterm infants. Methods: A total of 262 eligible extremely preterm infants underwent randomization; of these, 132 were assigned to the VA group and 130 to the control group. The infants were administered a solution of VA (1,500 IU/day), added to their enteral feeds as soon as minimal feeding was introduced and continued for 28 days or until discharge. Results: With no adverse effects occurring, serum VA of the VA-supplemented infants on Days 14, 28, and postmenstrual 36 weeks was higher than that of the placebo group (P < 0.001). No signs of VA toxicity or increased intracranial pressure were reported. The VA group had lower unadjusted rates of Type 1 retinopathy of prematurity (1.6 vs. 6.9%, P = 0.030) and bronchopulmonary dysplasia (18.9 vs. 33.8%, P = 0.008) than the control group. Regression analysis revealed an association between serum VA levels and risk of Type 1 retinopathy of prematurity (beta = −2.37). Conclusion: Vitamin A supplementation reduced VA deficiency in extremely preterm infants; it was associated with a decreased incidence of Type 1 retinopathy of prematurity and may also have a positive impact on reducing bronchopulmonary dysplasia.

Background There is a well‐known correlation between obesity, sedentary lifestyle, and breast cancer incidence and outcome. The Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) exercise study was a multicenter, randomized clinical trial and assessed the feasibility and efficacy of physical training in 50 breast cancer patients undergoing aromatase inhibitor treatment. Methods Postmenopausal, estrogen receptor‐positive breast cancer patients under aromatase inhibitor treatment were randomized 1:1 to counseling and unsupervised training for 48 weeks (unsupervised arm) or counseling and a sequential training (supervised arm) with a supervised phase (24 weeks) followed by unsupervised physical training (further 24 weeks). Primary endpoint was the individual maximum power output on a cycle ergometer after 24 weeks of exercise. A key secondary endpoint was the feasibility of achieving 12 METh/week (metabolic equivalent of task hours per week). Results Twenty‐three patients (92%) in the unsupervised arm and 19 patients (76%) in the supervised arm with early‐stage breast cancer completed the study. After 24 weeks, the supervised arm achieved a significantly higher maximum output in watt (mean 132 ± standard deviation [SD] 34; 95% confidence interval [CI] 117‐147) compared to baseline (107 ± 25; 95%CI 97‐117; P = 0.012) with a numerically higher output than the unsupervised arm (week 24 115 ± 25; 95%CI 105‐125; P = 0.059). Significantly higher METh/week was reported in the supervised arm compared to the unsupervised arm during the whole study period (week 1‐24 unsupervised: 18.3 (7.6‐58.3); supervised: 28.5 (6.7‐40.1); P = 0.043; week 25‐48; P = 0.041)). Conclusion This trial indicates that patients in an exercise program achieve higher fitness levels during supervised than unsupervised training.

Context Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post–renal transplant hyperglycemia (EPTH) ( 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.

BackgroundThe conventional dose rate of radiation therapy is 0.01–0.05 Gy per second. According to preclinical studies, an increased dose rate may offer similar anti-tumoral effect while dramatically improving normal tissue protection. This study aims at evaluating the early toxicities for patients irradiated with high dose rate pulsed proton therapy (PT).Materials and MethodsA single institution retrospective chart review was performed for patients treated with high dose rate (10 Gy per second) pulsed proton therapy, from September 2016 to April 2020. This included both benign and malignant tumors with ≥3 months follow-up, evaluated for acute (≤2 months) and subacute (>2 months) toxicity after the completion of PT.ResultsThere were 127 patients identified, with a median follow up of 14.8 months (3–42.9 months). The median age was 55 years (1.6–89). The cohort most commonly consisted of benign disease (55.1%), cranial targets (95.1%), and were treated with surgery prior to PT (56.7%). There was a median total PT dose of 56 Gy (30–74 Gy), dose per fraction of 2 Gy (1–3 Gy), and CTV size of 47.6 ml (5.6–2,106.1 ml). Maximum acute grade ≥2 toxicity were observed in 49 (38.6%) patients, of which 8 (6.3%) experienced grade 3 toxicity. No acute grade 4 or 5 toxicity was observed. Maximum subacute grade 2, 3, and 4 toxicity were discovered in 25 (19.7%), 12 (9.4%), and 1 (0.8%) patient(s), respectively.ConclusionIn this cohort, utilizing high dose rate proton therapy (10 Gy per second) did not result in a major decrease in acute and subacute toxicity. Longer follow-up and comparative studies with conventional dose rate are required to evaluate whether this approach offers a toxicity benefit.

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 (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 12 months (63%) after injury ( P = 0.04). Medial meniscal lesions were more likely to be repaired when surgery was performed 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.

AmaçPrimer dudak damak yarığı (DDY) onarımı, yaşam boyu en kritik aşamadır. DDY ameliyatı, ameliyata ve anesteziye bağlı komplikasyon risklerini içerir. Bu çalışmada, primer DDY cerrahisi sonrası erken dönemde meydana gelen komplikasyonların değerlendirilmesi ve bu durumları tetikleyen erken dönemdeki faktörlerin belirlenmesi amaçlanmıştır.Gereç ve YöntemBu çalışmaya 271 DDY hastasının 328 ameliyatı dahil edildi. Komplikasyonlar, ilk 3 günde ortaya çıkan ateş gibi komplikasyonlar minör komlikasyon olarak sınıflandırıldı. Palyatif bakımla tedavi edilemeyen veya yoğun bakıma transfer edilmesi gereken komplikasyonlar ise majör komplikasyonlar olarak kabul edildi. Erken komplikasyonların epidemiyolojisi ve nedensel bağlantısı istatistiksel olarak değerlendirildi.BulgularDudak damak yarığı nedeniyle ameliyat edilen tüm olguların %19'unda (n: 63) erken komplikasyonlar görüldü. Bunlar arasında minör komplikasyon oranı %9 (n: 25) idi. Anestezinin uzamasının ağızdan beslenmede yetersizlik gibi minör komplikasyonların artmasına neden olduğu belirlendi. Majör komplikasyonlar %11 (n: 38) oranında görüldü. Bu majör komplikasyonlar, bilateral dudak yarığı olanlarda, sendromik olgularda, damak yarığı olanlarda ve erkek hastalarda daha sıktı. Komplike vakaların ortalama hastanede kalış süresi 3.35 gündü. Komplike olmayan vakalarla karşılaştırıldığında hastanede kalış süresinde artış vardı (p, AimPrimary cleft lip and palate (CLP) repair is the most critical stage throughout lifetime. CLP surgery involves risks of surgery and anaesthesia related complications. In this study, it was aimed to evaluate complications occurred in early period after primary CLP surgery and to determine early factors that trigger these conditions.Materials and MethodsIn this study 328 surgeries of 271 CLP patients were included. Complications were classified as minor complications such as fever occurring within first 3 days. Complications that cannot be treated with palliative care or required transfer to intensive care were considered as major complications. Epidemiology and causal link of early complications were statistically evaluated.ResultsEarly complications were seen in 19% (n: 63) of all cases that operated for cleft lip and palate. Among them rate of minor complications were 9% (n: 25). It was determined that prolongation of anaesthesia lead to rising of minor complications such as deficiency in oral feeding. Major complications were observed in 11% (n: 38). These major complications were more common in bilateral cleft lip, syndromic, palate and male patients. Mean hospitalisation of complicated cases were 3.35 days. When compairing to noncomplicated cases there was increasing in hospitalisation time (p

Objectives 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. Methods 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. Results 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). Conclusions 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.

Objective 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. Methods 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. Main results 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. Conclusion 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.

Objectives The GETAFIX trial will test the hypothesis that favipiravir is a more effective treatment for COVID-19 infection in patients who have early stage disease, compared to current standard of care. This study will also provide an important opportunity to investigate the safety and tolerability of favipiravir, the pharmacokinetic and pharmacodynamic profile of this drug and mechanisms of resistance in the context of COVID-19 infection, as well as the effect of favipiravir on hospitalisation duration and the post COVID-19 health and psycho-social wellbeing of patients recruited to the study. Trial design GETAFIX is an open label, parallel group, two arm phase II/III randomised trial with 1:1 treatment allocation ratio. Patients will be randomised to one of two arms and the primary endpoint will assess the superiority of favipiravir plus standard treatment compared to standard treatment alone. Participants This trial will recruit adult patients with confirmed positive valid COVID-19 test, who are not pregnant or breastfeeding and have no prior major co-morbidities. This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. Patients must meet all of the following criteria: 1. Age 16 or over at time of consent 2. Exhibiting symptoms associated with COVID-19 3. Positive for SARS-CoV-2 on valid COVID-19 test 4. Point 1, 2, 3, or 4 on the WHO COVID-19 ordinal severity scale at time of randomisation. (Asymptomatic with positive valid COVID-19 test, Symptomatic Independent, Symptomatic assistance needed, Hospitalized, with no oxygen therapy) 5. Have >=10% risk of death should they be admitted to hospital as defined by the ISARIC4C risk index: https://isaric4c.net/risk 6. Able to provide written informed consent 7. Negative pregnancy test (women of childbearing potential*) 8. Able to swallow oral medication Patients will be excluded from the trial if they meet any of the following criteria: 1. Renal impairment requiring, or likely to require, dialysis or haemofiltration 2. Pregnant or breastfeeding 3. Of child bearing potential (women), or with female partners of child bearing potential (men) who do not agree to use adequate contraceptive measures for the duration of the study and for 3 months after the completion of study treatment 4. History of hereditary xanthinuria 5. Other patients judged unsuitable by the Principal Investigator or sub-Investigator 6. Known hypersensitivity to favipiravir, its metabolites or any excipients 7. Severe co-morbidities including: patients with severe hepatic impairment, defined as: • greater than Child-Pugh grade A • AST or ALT > 5 x ULN • AST or ALT >3 x ULN and Total Bilirubin > 2xULN 8. More than 96 hours since first positive COVID-19 test sample was taken 9. Unable to discontinue contra-indicated concomitant medications This is a multi-centre trial, patients will be recruited from in-patients and outpatients from three Glasgow hospitals: Royal Alexandra Hospital; Queen Elizabeth University Hospital; and the Glasgow Royal Infirmary. Intervention and comparator Patients randomised to the experimental arm of GETAFIX will receive standard treatment for COVID-19 at the discretion of the treating clinician plus favipiravir. These patients will receive a loading dose of favipiravir on day 1 of 3600mg (1800mg 12 hours apart). On days 2-10, patients in the experimental arm will receive a maintenance dose of favipiravir of 800mg 12 hours apart (total of 18 doses). Patients randomised to the control arm of the GETAFIX trial will receive standard treatment for COVID-19 at the discretion of the treating clinician. Main outcomes The primary outcome being assessed in the GETAFIX trial is the efficacy of favipiravir in addition to standard treatment in patients with COVID-19 in reducing the severity of disease compared to standard treatment alone. Disease severity will be assessed using WHO COVID 10 point ordinal severity scale at day 15 +/- 48 hours. All randomised participants will be followed up until death or 60 days post-randomisation (whichever is sooner). Randomisation Patients will be randomised 1:1 to the experimental versus control arm using computer generated random sequence allocation. A minimisation algorithm incorporating a random component will be used to allocate patients. The factors used in the minimisation will be: site, age (16-50/51-70/71+), history of hypertension or currently obsess (BMI>30 or obesity clinically evident; yes/no), 7 days duration of symptoms (yes/no/unknown), sex (male/female), WHO COVID-19 ordinal severity score at baseline (1/2or 3/4). Blinding (masking) No blinding will be used in the GETAFIX trial. Both participants and those assessing outcomes will be aware of treatment allocation. Numbers to be randomised (sample size) In total, 302 patients will be randomised to the GETAFIX trial: 151 to the control arm and 151 to the experimental arm. There will be an optional consent form for patients who may want to contribute to more frequent PK and PD sampling. The maximum number of patients who will undergo this testing will be sixteen, eight males and eight females. This option will be offered to all patients who are being treated in hospital at the time of taking informed consent, however only patients in the experimental arm of the trial will be able to undergo this testing. Trial Status The current GETAFIX protocol is version 4.0 12th September 2020. GETAFIX opened to recruitment on 26th October 2020 and will recruit patients over a period of approximately six months. Trial registration GETAFIX was registered on the European Union Drug Regulating Authorities Clinical Trials (EudraCT) Database on 15th April 2020; Reference number 2020-001904-41 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001904-41/GB). GETAFIX was registered on ISRCTN on 7th September 2020; Reference number ISRCTN31062548 (https://www.isrctn.com/ISRCTN31062548). Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (see Additional file 2).

Introduction:this research aimed to analyze nerve growth factor (NGF) contents as diagnostic tools for early disability in leprosy patients and the cut-off point value. Methods:research samples consisted of 79 leprosy patients with disability grade 0 or 1 who met the clinically approved inclusion criteria. The age of patients ranged from 14 to 50 years. For both sample groups, blood serum was collected to determine NGF concentration. NGF level was analyzed by enzyme-linked immunosorbent assay (ELISA) according to the manual guide of the kit insert from Cussabio®. Statistical analysis used SPSS 17 software for Windows. A comparison was performed with the Student's t-test, and the NGF concentration cut-off point was determined using a receiver operating characteristic (ROC) curve. Results:the research result demonstrated that NGF concentration in multibacillary leprosy with disability grade 0 was higher than in grade 1. Leprosy with disability grade 0 had an NGF content reaching 100.46 pg/mL, while those with grade 1 had a lower concentration of NGF at 30.56 pg/mL. The higher disability grade indicated a lower NGF concentration in the blood serum. Based on the ROC analysis result, the NGF cut-off was shown to be 81.43 pg/mL. This result indicated that low NGF in nerve and skin lesions of leprosy patients contributes to early peripheral nerve malfunction due toMycobacterium lepraeinfection. Conclusion:these results prove that NGF can be used as a marker of early disability in leprosy, with the cut-off value at 81.43 pg/mL.

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.

Background Early use of antimicrobials is a critical intervention in the treatment of patients with sepsis. The exact time of initiation is controversial and its early administration may be a difficult task in crowded emergency departments (ED). The aim of this study was to estimate, using a matched propensity score, the effect on hospital mortality of administration of antimicrobials within 1 or 3 hours, in patients admitted to the ED with sepsis. Methods This was a secondary analysis of a multicenter prospective cohort. Patients included in the study were older than 18 years, hospitalized between 2014 and 2016 with suspected sepsis, and admitted to ED of three tertiary care university hospitals in Medellín, Colombia. A propensity score analysis for administration of antimicrobials, both within 1 and 3 h of admission by the ED, was fitted with 28 variables related with clinical attention and physiological changes. As a sensitivity analysis, a logistic regression model was fitted for antimicrobial use adjusted both by propensity score and confounding variables. Results The study cohort was composed of 2454 patients with a median age of 62 years (IQR = 46–74). Among them, 32% (n = 781) received antibiotics within 3 h and 14% (n = 340) within the first hour. The main diagnoses were urinary tract infection (28%, n = 682) and pneumonia (27%, n = 671). Blood cultures were obtained in 87% (n = 2140) and yielded positive in 29% (n = 629), mainly with Escherichia coli (37%, n = 230), Staphylococcus aureus (21%, n = 132), and Klebsiella pneumoniae (10.2%, n = 64). The hospital mortality rate was 11.5% (n = 283). There were no significant differences in mortality, after adjustment, using antimicrobials either in the first hour (OR 1.03; 95% CI = 0.63; 1.70) or 3 h (OR 0.85; 95% CI = 0.61; 1.20). There were no changes with different models for sensitivity analysis. Conclusions Despite the obvious constraints given for sample size and residual confounding, our results suggest that we need a more comprehensive approach to sepsis and its treatment, considering early detection, multiple interventions, and goals beyond the simple time-to-antimicrobials.

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

Whether breast-conserving therapy (BCT) should be chosen as a local treatment for young women with early-stage breast cancer is controversial. This study compared the survival benefits of BCT or mastectomy in young women under 40 with early-stage breast cancer and further explored age-stratified outcomes. This study investigated whether there is a survival benefit when young women undergo BCT compared with mastectomy. The characteristics and prognosis of white women under 40 with stage I–II breast cancer from 1988 to 2016 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. These women were either treated with BCT or mastectomy. The log-rank test of the Kaplan–Meier survival curve and Cox proportional risk regression model were used to analyze the data and survival. The analysis was stratified by age (18–35 and 36–40 years). A total of 23,810 breast cancer patients were included, of whom 44.9% received BCT and 55.1% underwent mastectomy, with a median follow-up of 116 months. Patients undergoing mastectomy had a higher tumor burden and younger age. By the end of the 20th century, the proportion of BCT had grown from nearly 35% to approximately 60%, and then gradually fell to 35% into the 21st century. Compared with the mastectomy group, the BCT group had improved breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.917; 95% CI, 0.846–0.995, P = .037) and overall survival (OS) (HR 0.925; 95% CI, 0.859–0.997, P = .041). In stratified analysis according to the different ages, the survival benefit of BCT was more pronounced in the slightly older (36–40 years) group while there was no significant survival difference in the younger group (18–35 years). In young women with early-stage breast cancer, BCT showed survival benefits that were at least no worse than mastectomy, and these benefits were even better in the 36 to 40 years age group. Young age may not be a contraindication for BCT.

As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy.The aim of this retrospective intent-to-treat analysis of the hospitalized patients who started off-label treatment with LPV/ritonavir (LPV/r)+HCQ between 21 February and 20 March 2020 was to compare the rate of clinical improvement between those who started the treatment within five days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). The association between the timing of treatment and the probability of 30-day mortality was also assessed using uni- and multivariable logistic models.The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Gray’s test P = 0.213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment because of severe gastrointestinal disorders attributable to LPV/r.The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.

Background In here, we constructed personalized models for predicting breast cancer (BC) recurrence according to timing of recurrence (as early and late recurrence). Methods An efficient algorithm called group LASSO was used for simultaneous variable selection and risk factor prediction in a logistic regression model. Results For recurrence 5 years, stage 2 cancer (OR 1.67, 95% CI = 1.31–2.14) and radiotherapy+mastectomy (OR 2.45, 95% CI = 1.81–3.32) were significant predictors; furthermore, relative to mastectomy without radiotherapy (as reference for comparison), quadranectomy without radiotherapy had a noticeably higher odds ratio compared to quadranectomy with radiotherapy for recurrence > 5 years (OR 7.62, 95% CI = 1.52–38.15 vs. OR 1.75, 95% CI = 1.32–2.32). Accuracy, sensitivity, and specificity of the model were 71%, 78.8%, and 55.8%, respectively. Conclusion For the first time, we constructed models for estimating recurrence based on timing of recurrence which are among the most applicable models with excellent accuracy (> 80%). Electronic supplementary material The online version of this article (10.1186/s12957-018-1489-0) contains supplementary material, which is available to authorized users.

Eren, Erdal/0000-0002-1684-1053; Ercan, Oya/0000-0001-7397-2837; camtosun, emine/0000-0002-8144-4409; Turkkahraman, Doga/0000-0002-7472-5712 WOS:000498876500002 PubMed ID: 30991789 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 nonsyndromic early onset severe obesity. Methods: Children with severe (body mass index-standard deviation score >3) and early onset (

ObjectivesTo provide updated and more detailed pooled intrauterine device expulsion rates and expulsion risk estimates among women with postpartum intrauterine device placement by timing of insertion, delivery type, and intrauterine device type to inform current intrauterine device insertion practices in the United States.Data sourcesWe searched PubMed, Cochrane Library, and ClinicalTrials.gov through June2019.Study eligibility criteriaWe included all studies, of any study design, that examined postpartum placement of Copper T380A (copper) or levonorgestrel-containing intrauterine devices that reported counts of expulsion.Study appraisal and synthesis methodsWe evaluated intrauterine device expulsion among women receiving postpartum intrauterine devices in the "immediate" (within 10 minutes), "early inpatient" (>10 minutes to

Acute liver failure (ALF) is a rare but life-threatening illness with multiple organ failure. The short-term mortality rate exceeded 80 % despite modern approaches in treatment. Drugs, infections by hepatic viruses and toxins are the most common causes of ALF. Progressive jaundice, coagulation disorder and hepatic encephalopathy are dominated as a clinical signs of the illness. We present a case of a 36-year-old Caucasian woman hospitalized in ICU due to yellow discoloration of the skin and sclera, severe disseminated coagulopathy and hemodynamic instability. ALF is developed due to Hepatitis B Virus infection, resulting in hepatic toxicity as well as coma. General condition rapidly improved after applying of Molecular Adsorbent Recirculating System (MARS), an extracorporeal liver support system based on albumin dialysis. It is relatively expensive treatment that is used for the patient with hepatic encephalopathy grade 3 or 4 in our institution. In conclusion, an early administration of MARS significantly reveals subjective and objective clinical improvement in the case we presented.

Background and Objective: Tracheostomy in neurosurgical patients has been shown in various studies to lower the length of ICU stay and the length of hospital stay by decreasing the incidence of ventilator associated pneumonia. In this regard, we wanted to evaluate the outcome of neurosurgical ICU patients based on timing of tracheostomy and ventilator associated pneumonia.Methods: This is a retrospective single centre study performed over a period of two and a half years. Early tracheostomy was defi ned as those done three days of intubation or earlier and late as those done then after. Statistical analysis was done using SPSS.Results: There were 56 patients over the study period of which 18 patients underwent early tracheostomy and 38 patients underwent late tracheostomy. There was no statistically significant difference between the two groups with regards to the length of ICU stay, the length of hospital stay or the length of tracheostomy tube in situ. But based on tracheal aspirate culture positivity, length of tracheostomy tube in situ was signifi cantly longer in those with positive bacterial cultures.Early tracheostomy does not improve neurosurgical outcome while documented pneumonia prolongs the length of tracheostomy tube in situ.Nepal Journal of Neuroscience 15:19-22, 2018

The aim of this study is to report and analyze the factors related with earlier occurrence of silicone oil (SO) emulsification in patients underwent pars plana vitrectomy and SO injection in our hospital. We retrospectively reviewed consecutive case series undergone both SO injection and removal in our hospital, and 182 ones were eligible. Possible related independent factors included: macula status (on/off), concomitant phacoemulsification with the surgery of SO tamponading, concomitant status of proliferative vitreoretinopathy, combined surgery of retinotomy, time to have emulsification (

Objective: To explore the difference in outcomes of medium-sized lobar hematomas evacuated in early versus delayed fashion among unconscious noncomatose individuals. Methods: A retrospective analysis of demographic, clinical, and radiological data of unconscious patients admitted with lobar hematomas during 18 years was performed. Time to surgery was compared in various patient variables and characteristics. Outcome groups (favorable and poor) were also compared to find out any association with surgery timing, as well as potential indicators of outcome and mortality. Results: The mean follow-up period in this study was 7.5 months after discharge. Two-thirds of the patients carried favorable prognosis at final follow-up with mortality (7.3%) included among poor cases. Time to surgery was not associated to any of the patient characteristics, except for international normalized ratio and associated chest problems which represented the main indicators of delayed surgery. Rebleeding after evacuation was associated with shorter time to surgery in clots ≤35 cc but not in the whole group. Poor outcome was significantly associated with higher basal glucose levels, bigger hematomas, rebleeding after surgery, and delayed evacuation of clots ≤35 cc. The presence of mild intraventricular hemorrhage (IVH) per se was not associated with increased mortality or poor outcome; however, its volume was. Conclusion: Smaller lobar hematomas (≤35 cc) in unconscious adults (Glasgow Coma Scale 8–13) may be managed with initial conservative treatment, while larger hematomas (≤35 cc) are better evacuated as early as possible. Basal glucose levels and volume of mild IVH should be considered in the future management planes.

ASSESSMENT OF THE OUTCOME OF EARLY VERSUS DELAYED SPICA CAST IN THE TREATMENT OF CLOSED FEMORAL SHAFT FRACTURE IN CHILDREN Hamid A Jaff MB,ChB, DM, FICMS, Orthopedic Surgeon, College of Medicine, University of Sulaimaniyah, IRAQ. Abstract This study aimed to assess the results of early versus late spica cast in the treatment of femoral shaft fracture in children. This is a descriptive study performed at Al-Sulaimaniya Teaching Hospital during the period between June 2009 and October 2010. Twenty eight patients with a mean age of five years ranged (2-8 years) with closed isolated femoral shaft fractures were included in this study. They were four females and twenty four males. Fifteen patients had left sided fractures while right sided fractures were in thirteen patients. Patients having compound fractures and those with associated injuries were excluded from the study. Ten patients were treated by skin traction for about 2-3 weeks then hip spica cast was applied. The other 18 patients treated by early spica within 2-5 days. All patients were followed for a period of about 4 months after removal of spica cast. The study reveals that boys are affected more than girls. The causes of the fracture in this study were 15 cases (53.6%) fall from height; 8 cases (28.6 %) road traffic accident and lastly 5 cases (17.9%) for other causes like direct trauma. Average duration of skin traction in delayed Spica cast group was 2-3 weeks. Immediate complications after removal of the spica; patients treated with early spica were 3 cases for side way angulation, 1 case for shortening, while for anterior angulation 1 case. Patients treated with delayed spica following skin traction complicated by anterior angulation was 1 case and side way angulation was 1 case while no case of shortening reported. The patients considered here to have a shortening or angulation are only those having a deformity of more than accepted limits (20 mm shortening, 15 degrees side way angulation and 20 degrees for anterior angulation), but after 10 months of follow up for all of the patients, most of the initially observed complications were corrected to the accepted limits. The shortening which was reported initially overcomed by overgrowth and only 0.8 cm length discrepancy was there. For both anterior and side way angulation, they were within the accepted limits. In early spica, the hospitalization ranged from 2-5 days; while in delayed spica, the hospitalization time ranged from 16-23 days. It is concluded that little significant difference in late outcome between early and delayed spica cast application regarding the complications of treatment and functional outcome, but early spica decreased the hospitalization time and the cost of treatment significantly.

Alissar El Chediak,1 Raafat S Alameddine,1 Ayman Hakim,1 Lara Hilal,2 Sarah Abdel Massih,1 Lana Hamieh,3 Deborah Mukherji,1 Sally Temraz,1 Maya Charafeddine,1 Ali Shamseddine1 1Division of Hematology/Oncology, Department of Internal Medicine, 2Department of Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon; 3Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA, USA Background: Several retrospective studies have reported that younger age at presentation is associated with a worse prognosis for nonmetastatic breast cancer patients. In this study, we prospectively assessed the association between different baseline characteristics (age, tumor characteristics, mode of treatment, etc) and outcomes among newly diagnosed nonmetastatic Lebanese breast cancer patients.Methods: We recruited a sample of 123 women newly diagnosed with nonmetastatic breast cancer presenting to American University of Beirut Medical Center. Immunohistochemical, molecular (vitamin D receptor, methylene tetrahydrofolate reductase polymorphisms), and genetic assays were performed. Patient characteristics were compared by age group (40 years (5.2%). A wide immunohistochemical panel included Ki-67, cyclin B1, p53, platelet-derived growth factor receptor, and vascular endothelial growth factor receptor, and did not reveal any significant difference in these markers between the two age groups. Older patients had a larger percentage of Luminal A than younger patients. On multivariate analysis including age, stage, grade, and subtype, only age 40 years was 90%, and for patients

Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Background Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is associated with high mortality. One of the strategies to reduce the mortality in patients with CRAB infections is to use intravenous colistin early but the effect of this strategy has not been proven. Therefore, we investigated the association of early colistin therapy with 28-day mortality in patients with CRAB bacteremia. Methods This retrospective multicenter propensity score-matching analysis was conducted in the Korea by reviewing the medical records of adult patients with CRAB bacteremia between January 2012 and March 2015. Early colistin therapy was defined as intravenous colistin administration for > 48 hours within five days after the blood culture collection. To identify the risk factors associated with the 28-day mortality in CRAB bacteremia, the clinical variables of the surviving patients were compared to those of the deceased patients. Results Of 303 enrolled patients, seventy-six (25.1%) patients received early colistin therapy. The 28-day mortality was 61.4% (186/303). Fatal or rapidly-fatal McCabe classifications, intensive care unit admission, Sequential Organ Failure Assessment scores ≥ 8, vasopressor use, and acute kidney injury were statistically independent poor prognostic factors. Catheter-related infection and early colistin therapy (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.21–0.94) were independent favorable prognostic factors associated with 28-day mortality in patients with CRAB bacteremia. Early colistin therapy was still significantly associated with lower 28-day mortality in the propensity score-matching analysis (aOR, 0.31; 95% CI, 0.11–0.88). Conclusion This study suggests that early colistin therapy might help reduce the mortality of patients with CRAB bacteremia., Graphical Abstract

Objectives: The study aimed to evaluate biomarkers facilitating early axial-spondyloarthritis (axSpA) diagnosis and disease activity and imaging indices correlated. Materials and Methods: Seventy-five patients with low back pain (LBP) (≥3 months, ≤2 years, onset ≤45 years) participating in the Italian arm of the SpondyloArthritis-Caught-Early (SPACE) study underwent a physical examination, questionnaires, laboratory tests, spine, and sacroiliac joints (SIJ) X-rays and magnetic resonance imaging (MRI) at baseline and during a 24-months follow-up. Two expert rheumatologists formulated axSpA diagnosis and assessed fulfillment of Assessment of SpondyloArthritis International Society (ASAS) criteria. Disease activity and physical functioning were assessed using imaging, clinical, and serological indices. Spine and SIJ MRI and X-rays were scored independently by 2 readers following the Spondyloarthritis Research Consortium of Canada (SPARCC), mSASSS, and mNY-criteria. Patients were classified in accordance to ASAS criteria as: 21 patients classified according to axSpA imaging arm; 29 patients classified according to axSpA clinical ± imaging arm; 25 patients not fulfilling ASAS criteria. Results: At baseline biomarker levels were not significantly increased in any of the patient groups. Instead, a significant decrease of all functional and disease activity indices from baseline to 24 months was observed in all the three groups. In the same period, there were no significant variation in the serological markers values within each group. The correlations between IL-17 and IL-23 and clinical and functional indices were not significant. On the other hand, significant correlations were found between IL-22 and Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BASG1), Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS pain); MMP3 and mSASSS; MMP3 and hsCRP. Conclusions: Although not significantly higher in any of the cohorts, IL-22, MMP3, and hsCRP values correlated with some disease activity indices and with mSASSS. Further studies are warranted to confirm these preliminary findings.

Emerging literature suggests that delayed identification of childhood asthma results in an increased risk of long-term and various morbidities compared to those with timely diagnosis and intervention, and yet this risk is still overlooked. Even when children and adolescents have a history of recurrent asthma-like symptoms and risk factors embedded in their medical records, this information is sometimes overlooked by clinicians at the point of care. Given the rapid adoption of electronic health record (EHR) systems, early identification of childhood asthma can be achieved utilizing (1) asthma ascertainment criteria leveraging relevant clinical information embedded in EHR and (2) innovative informatics approaches such as natural language processing (NLP) algorithms for asthma ascertainment criteria to enable such a strategy. In this review, we discuss literature relevant to this topic and introduce recently published informatics algorithms (criteria-based NLP) as a potential solution to address the current challenge of early identification of childhood asthma.

This case report aims to critically analyse the evidence surrounding early extubation in the post-operative phase following complex congenital cardiac surgery. Child A was an 8 year old female who had undergone complex congenital cardiac surgery during an international surgical charity mission. On admission to the paediatric intensive care unit Child A appeared to be in good condition and no major complications had occurred intra-operatively. This was considered alongside the situational pressures of resource limitations and the mission's aim to offer surgery to as many children as possible during the available time frame. The decision was made by the team that Child A was a suitable candidate for ‘early extubation.’ Some members of the team were uncomfortable with this approach and felt it could lead to poorer outcomes for patients. Current evidence surrounding early extubation both within international surgical mission trips to low-income and middle-income countries and established cardiac centres within high-income countries is examined and discussed alongside the context of resource limitation. Although the process and implications of early extubation following cardiac surgery needs further research, on the basis of the evidence currently available clinicians could potentially encourage the use of early extubation within clinical practice (for appropriately selected patients) through the utilisation of a multidisciplinary approach, both within the UK and during international surgical charity missions to low-income and middle-income countries.

Introduction Relapse is common after treatment discontinuation for patients with moderate-to-severe psoriasis. The objective of this study was to understand the remission duration and long-term outcomes in psoriasis patients after biologic withdrawal. Methods We retrospectively included the follow-up data of 184 patients with moderate-to-severe psoriasis after the end of 11 biologic or tofacitinib trials conducted between 2004 and 2016. Results Among the 232 treatment courses, 95 achieved (psoriasis area and severity index) PASI 75 at the end of the studies. At 6 months after treatment discontinuation, the systemic treatment-free rates of our patients who entered the PRESTA, PRISTINE, PEARL, ERASURE, CLEAR, the global tofacitinib study, and the IXORA-P study were 66.7%, 66.7%, 75.0%, 16.7%, 22.2%, 33.3%, and 29.2%, respectively. Pooled data showed a serious adverse event incidence rate of 1.5/100 person-years. The proportions of systemic treatment-free episodes were 16.8%, 7.4%, 4.3%, 3.2%, and 3.2% at 1, 2, 3, 4, and 5 years, respectively. Biologics were reinitiated in 41.9%, 66.7%, 77.1%, 83.5%, and 86.1% at 1, 2, 3, 4, and 5 years, respectively. Multivariate generalized estimating equation (GEE) regression analysis demonstrated that predictors for a longer relapse-free duration were baseline PASI, PASI improvement, biologic naivety, and early biologic intervention. Patients who received early biologic intervention, who achieved PASI 90, and who were biologic naive showed significantly higher relapse-free rate by Kaplan–Meier analysis with log rank test. Conclusions Systemic treatment was required in 86.1% of patients within 12 months after biologic withdrawal and biologics were reinitiated in 77.1% of patients after 3 years. However, early biologic administration within 2 years after diagnosis demonstrated a lower risk of relapse in patients with moderate-to-severe psoriasis.