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Background: Pakistan has got a very high prevalence of myocardial infarction (MI). MI presents at pretty young age in this country. The objective of present study was to determine the frequency of common risk factors associated with early development of MI in middle aged adults of less than 45 years. Methods: It was a cross sectional study conducted in the Cardiology department of Ayub Teaching Hospital (ATH) Abbottabad from 23rd June 2015 – 10th July 2016. A total of 255 consecutive patients diagnosed with MI admitted to the Cardiology Unit of ATH, Abbottabad. A detailed medical history and general physical examination of the patients was carried out with an emphasis on recording the presence or absence of common risk factors of MI in these patients. All routine investigations (Blood Complete Picture, Urea, Creatinine, Blood Sugar & Lipid Profile) were done. Results: Mean age of the subjects was 39.98±4.61 SD. The frequency of risk factors in descending order was smoking in (38.8%), obesity in (29.4%) and essential hypertension in (21.6%) of the patients. Other risk factors of MI in this study were diabetes mellitus (19.2%), family history of ischemic heart disease (IHD) was (18.8%) and disproportionate dyslipidemias in (12.9%). Sex of patients (male predominance) was found to be significantly associated with diabetes, smoking and dyslipidemia (p

To examine our outpatient urologic surgery cohort for trends in opioid consumption, given the lack of consensus on opioid prescription after outpatient urologic procedures. While opioids have a role in multimodal postoperative analgesia, there is emerging data that they may not be routinely required after pediatric surgery.Data on opioid use was prospectively collected over 16 months via postoperative telephone calls to caregivers of patients undergoing outpatient urologic surgery. Patient characteristics, surgery type, analgesia, and opioid prescription and usage information were recorded. Patients were prescribed as needed oxycodone and scheduled acetaminophen and ibuprofen for 48 hours, then as needed. The relationships between the log mean of the number of opioid doses used and age, type of surgery, race, and opioid prescription were modelled using negative binomial regression with the robust standard errors.Two hundred sixty-five patients were included. They were predominantly male with median age 2.6 years. The mean number of opioid doses prescribed per patient was 5.8 (SD 2.8, range 3-20). Over half of patients used no opioids, and mean opioid use was one dose. Those prescribed5 doses took on average 3.4 times more doses compared to those prescribed5 (P = .0003), and this was the only factor significantly associated with the amount of opioid used.Our findings suggest that opioids are over-prescribed after outpatient pediatric urologic surgery, with 95% of patients having leftover medication and 54% not using any opioids at all. While opioid requirements were low across all sub-cohorts, patients who were prescribed more opioid doses used significantly more doses.

Epidemiological studies have provided varying prevalence estimates of trichotillomania (TTM) and other hair-pulling behaviors. We performed a systematic review and meta-analysis to provide data-driven prevalence estimates of TTM and hair-pulling. PubMed, PsycInfo and Embase were searched on June 2020 (updated in November 2021). Studies reporting the frequency of TTM defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria or hair-pulling behaviors were included. Prevalence data was extracted for both genders, and female-to-male odds ratios (OR) were computed for TTM and any hair-pulling behaviors. Data were pooled through random-effects meta-analyses. Of the 713 records identified through database searches, 30 studies involving 38,526 participants were included. Meta-analyses indicated TTM had a prevalence of 1.14% (95% CI 0.66%, 1.96%), while any hair-pulling behavior had a prevalence of 8.84% (95% CI 6.33%, 12.20%). Meta-analyses demonstrated females were at an increased risk of any hair-pulling when noticeable hair loss was required (OR = 2.23, 95% CI 1.60, 3.10, p 0.0001), but not of any hair-pulling when noticeable hair loss was not required (OR = 0.90, 95% CI 0.72, 1.64, p = 0.33). Meta-analyses did not indicate female preponderance in TTM (k = 10; N = 22,775; OR = 1.29; 95% CI 0.91, 1.83; I

OBJECTIVE To perform a detailed analysis of the epidemiology, tumor biology, treatment, overall survival, and quality of life in a young patient (age ≤45 years) cohort with oral squamous cell carcinoma (OSCC). STUDY DESIGN A retrospective cohort study between 1992 and 2017 at an academic tertiary care center. RESULTS In total, 80 patients were included (36 female and 44 male) with stage I (American Joint Committee on Cancer eighth ed.) disease and lateral tongue was most common presentation. Mean follow-up was 6.28 years. The overall disease recurrence rate was 28.7% (23 of 80). Human papillomavirus was positive in 22% of patients tested. Free flap reconstruction was not associated with improved margin status (P = .62) but significant for recurrent disease (P < .04). Overall 2-year survival was significantly poorer in patients with close/positive margin status and free flap reconstruction. Patients with early-stage disease (stage II) requiring adjuvant radiotherapy, chemotherapy (all stages), or flap reconstruction (Stage III patients) had significantly worse 5-year survival rates. CONCLUSIONS OSCC in young patients (age ≤45 years) is an increasingly more common disease that occurs in patients without known risk factors. Despite their earlier presentation of disease pathology, constant vigilance and standard aggressive treatment similar to other age groups will result in similar and improved outcomes and survival.

Objective: To evaluate the effectiveness of hand-hygiene training on handwashing practices among schoolchildren. Method: The quasi-experimental study was conducted from 1st August- 2018 to 5th October- 2018 in four secondary schools in Peshawar and Kohat districts of Khyber Pakhtunkhwa, Pakistan, and comprised male students grades 5, 6, 7, 9 and 10. They were given a live demonstration about the standard steps of hand-hygiene as per the World Health Organisation checklist, and they were shown the steps in pictorial form as well to reinforce the message. Pre- and post-intervention scores were recorded on the 14- point checklist. Data analysed using SPSS 23. Results: There were 200 boys with a mean age of 13.23±0.92 years (range: 11-16 years); 87(43.5%) of them being from grade 7. Post-intervention score increased significantly compared to the baseline (p

Context.— The pathologic nodal staging of prostatic adenocarcinoma is binary for regional lymph nodes. Stages pN0 and pN1 indicate the absence or presence of regional nodal metastasis, respectively, whereas patients with metastasis to nonregional lymph nodes are staged as pM1a. Objective.— To determine the risk of recurrence of pN1 prostatic adenocarcinoma patients based on the extent of nodal tumor burden. Design.— We retrospectively reviewed pN1 patients with prostatic adenocarcinoma managed with radical prostatectomy seen between 2011 and 2019. Kaplan-Meier and Cox regression analyses were performed to compare disease-free survival. Results.— Ninety-six patients were included (median [interquartile range] age, 62 years [57–67 years]; 70 of 96 [73%] White). On univariate analysis, age >65 years (P = .008), ≥2 positive regional lymph nodes (P < .001), and a maximum size of the tumor deposit ≥2 mm (P = .004) were significantly associated with an unfavorable outcome. Controlling for age, stage, metastatic deposit size, margin status, and the presence of extranodal extension, patients with ≥2 positive regional lymph nodes were 3.03 times more likely (95% confidence interval, 1.39–6.60; P = .005) to have an unfavorable outcome. Patients with pN1M1a stage showed a disease-free survival similar to that of pN1M0 patients, after controlling for the number of positive regional lymph nodes (P = .36). Conclusions.— Overall, pN1 patients with ≥2 positive regional lymph nodes are 3 times more likely to have an unfavorable outcome. The results suggest a benefit in further stratifying patients with metastatic prostatic adenocarcinoma to the lymph nodes into prognostically significant risk categories that could help the treating clinicians tailor subsequent patient follow-up and therapy.

We aimed to assess and compare autonomic function in Parkinson's disease (PD) associated with the leucine-rich repeat kinase (LRRK2) G2019S mutation (LRRK2-PD) and non-LRRK2 PD, by the study of heart rate variability (HRV) and sympathetic skin responses (SSR).In a cross-sectional three-year study, fifty LRRK2-PD and fifty clinically matched non-LRRK2 PD patients were included. Cardiac parasympathetic functions were assessed using heart rate variation to deep breathing (HR-DB), to the Valsalva maneuver (HR-V) and to standing (HR-S) and the sympathetic autonomic system by sympathetic skin responses (SSR).Neurophysiological, parasympathetic and sympathetic dysautonomia were found in 78%, 69% and 37% of all PD patients respectively. Rates of dysautonomia in the LRRK2-PD and non-LRRK2 PD patient subgroups were 76% vs 80% (p = 0.405) for neurophysiological, 62% vs 76% (p = 0.123) for parasympathetic and 38% vs 36% (p = 0.500) for sympathetic dysautonomia. HR-S was the most frequently altered parameter in both groups, and was significantly associated with the tremor-dominant (TD) motor phenotype of PD in the total cohort (p = 0.004) and in LRRK2-PD (p = 0.015). In LRRK2-PD patients, female gender was associated with parasympathetic dysfunction (p = 0.024), and with altered HR-DB (p = 0.022). Early-onset parkinsonism was also significantly associated with preserved neurophysiological autonomic functions (p = 0.044) in LRRK2-PD. In non-LRRK2 PD patients, male gender was associated with early parasympathetic (p = 0.043) and sympathetic dysfunction (p = 0.007).Our study showed a roughly similar neurophysiological autonomic profile in non-LRRK2 PD and LRRK2-PD. The latter had some peculiarities with more marked parasympathetic dysfunction and more altered HR-DB in females, more altered HR-S in the TD-motor phenotype, and preserved autonomic functions in early-onset parkinsonism. These preliminary findings would require further investigations on larger genetically homogeneous cohorts to explore the multiple facets of autonomic dysfunction in PD.

The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role.A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue.Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity-urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits.A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.

Background Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. Objective To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. Design Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tonsberg]). (ClinicalTrials.gov: NCT01778738). Setting Tertiary care obesity center in Norway. Participants 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). Intervention From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. Measurements The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. Results Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. Limitations Single-center study, short follow-up time, and lack of power for secondary outcomes. Conclusion With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. Primary funding source Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension.This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission.A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04).This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels. An interquartile range (IQR) increase of 18.12 μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

Background Intraparenchymal hemorrhage (IPH), possibly due to reperfusion, after evacuation of a cranial chronic subdural hematoma (cSDH) is a known phenomenon. However, it is sparingly reported and not well understood. Methods An illustrative case series is presented. A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify all previously reported cases. Results A total of 48 cases were analyzed. Males were 85.4% of the population, and the mean age was 67.5 years. Pre-existing head trauma and hypertension were the most common comorbidities. Headache was a presenting symptom in 60.4% of cases. Midline shift was explicitly stated in 54.2% of cases. Initial burr hole alone was performed 75.0% of the time, whereas craniotomy alone was performed in 16.7% of cases. Any initial craniotomy patients were associated with a modified Rankin Scale score of 5 (P = 0.03). The IPH was located in the cerebral hemisphere in 62.5% of cases and more likely to occur ipsilateral to a unilateral cSDH (P = 0.02). The IPH occurred a mean 1.9 days after surgery, and 50.0% occurred within 24 hours of initial intervention. The median modified Rankin Scale at discharge was 2. The mortality rate was 25%. Lastly, a multifactorial reperfusion pathophysiology was proposed. Conclusion IPH after cSDH evacuation is associated with significant morbidity and mortality. Prompt recognition, regulating blood pressure, controlling the amount and rate of extra-axial fluid drained, and a meticulous surgical technique are critical to optimize the care of patients with cSDH and reduce the rate of postoperative IPH.

Percutaneous closure of congenital ventricular septal defects (VSDs) represents a promising alternative to surgery with lower rate of complications and shorter hospital stay. Its main limitation is the choice of the appropriate device for each type of defect.To report the experience of the service of cardiology (Sahloul hospital, Sousse, Tunisia) in percutaneous closure of congenital VSDs with Amplatzer Duct Occluder II (ADOII).This was a retrospective, monocentric study, conducted from January 2013 to December 2017. The study included patients treated by percutaneous closure of congenital VSDs with the ADOII device.Twelve patients (6 boys; 6 girls) were included. The mean±SD of patients' age and weight were 65±41 months and 23±10 kg, respectively. VSDs were peri-membranous (n=9) and muscular (n=3), and defects were restrictive (n=11) and non-restrictive (n=1). The mean (minimum-maximum) size of VSDs was 4.72 (3-6) mm. Eleven ADOII prostheses were successfully implanted. One failure procedure was noted with migration of the device into the pulmonary artery. A second child with perimembranous defect developed transient atrioventricular block. No deaths occurred.The present early experience shows that percutaneous closure with ADOII device of perimembranous and trabecular VSDs is safe and effective.

The applications of exogenous hormones in different species for the induction of oocyte production, final oocyte maturation (FOM), and spawning for their reproduction is getting more attention day by day. The current preliminary research work was carried out to induce breeding in Clarias gariepinus, commonly known as African catfish, imported from Thailand. Single doses of two hormones as Ovaprim and human menopausal gonadotropin (hMG) were used and the research work was carried out at Muzaffargarh Fish Hatchery Punjab, Pakistan. A total of twenty-four (n = 24) C. gariepinus were selected having body weight approximately 2 kg and divided into two main groups based on gender as male (n = 12) and female (n = 12). For milt collection, all males were treated with Ovaprim 0.5 mg/kg body weight (b.w.) and female fish were divided into three groups as A, B, and C with four (n = 4) fish in each group. Group A was injected with only normal saline (control group) while fish in group B and group C were treated with hMG at 0.5 mg/kg b.w. and Ovaprim 0.5 mg/kg b.w., respectively. Then, after 6 h of hormone injections until 48 h, spawned eggs, eggs’ weight, fertilization rate, hatching rate, survival rate, fecundity, and deformed larvae were investigated. The results revealed that Ovaprim injection significantly (p

BACKGROUND: The COVID-19 pandemic has exacerbated disparities in poverty and illness for people in vulnerable circumstances in ethnocultural communities. We sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform intersectoral advocacy and community action. METHODS: The Illuminate Project used participatory action research, with cultural health brokers as peer researchers, from Sept. 21 to Dec. 31, 2020, in Edmonton, Alberta. Twenty-one peer researchers collected narratives from members of ethnocultural communities and self-interpreted them as they entered the narratives into the SenseMaker platform, a mixed-method data collection tool. The entire research team analyzed real-time, aggregate, quantitative and qualitative data to identify emerging thematic domains, then visualized these domains with social network analysis. RESULTS: Brokers serving diverse communities collected 773 narratives. Identified domains illuminate the evolving and entangled impacts of COVID-19 including the following: COVID-19 prevention and management; care of acute, chronic and serious illnesses other than COVID-19; maternal care; mental health and triggers of past trauma; financial insecurity; impact on children and youth and seniors; and legal concerns. We identified that community social capital and cultural brokering are key assets that facilitate access to formal health and social system supports. INTERPRETATION: The Illuminate Project has illustrated the entangled, systemic issues that result in poor health among vulnerable members of ethnocultural communities, and the exacerbating effects of COVID-19, which also increased barriers to mitigation. Cultural brokering and community social capital are key supports for people during the COVID-19 pandemic. These findings can inform policy to reduce harm and support community resiliency.

Site-specific variation in colorectal cancer (CRC) incidence, biology and prognosis are poorly understood. We sought to determine whether common genetic variants influencing CRC risk might exhibit topographical differences on CRC risk through regional differences in effects on gene expression in the large bowel mucosa. We conducted a site-specific genetic association study (10,630 cases, 31,331 controls) to identify whether established risk variants exert differential effects on risk of proximal, compared to distal CRC. We collected normal colorectal mucosa and blood from 481 subjects and assessed mucosal gene expression using Illumina HumanHT-12v4 arrays in relation to germline genotype. Expression quantitative trait loci (eQTLs) were explored by anatomical location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects - risk of distal CRC (OR=1.20, P=8.20x10-20 ) with negligible effects on proximal CRC risk (OR=1.05, P=0.10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference=10, P=3.48x10-57 ). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest trans-eQTL signals in proximal colonic mucosa (e.g. AKAP14, beta=0.61, P=5.02x10-5 ) and opposite signals in distal mucosa (AKAP14, beta=-0.17, P=0.04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa. Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes. This article is protected by copyright. All rights reserved. Site-specific variation in colorectal cancer (CRC) incidence, biology and prognosis are poorly understood. We sought to determine whether common genetic variants influencing CRC risk might exhibit topographical differences on CRC risk through regional differences in effects on gene expression in the large bowel mucosa. We conducted a site-specific genetic association study (10,630 cases, 31,331 controls) to identify whether established risk variants exert differential effects on risk of proximal, compared to distal CRC. We collected normal colorectal mucosa and blood from 481 subjects and assessed mucosal gene expression using Illumina HumanHT-12v4 arrays in relation to germline genotype. Expression quantitative trait loci (eQTLs) were explored by anatomical location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects - risk of distal CRC (OR=1.20, P=8.20x10-20 ) with negligible effects on proximal CRC risk (OR=1.05, P=0.10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference=10, P=3.48x10-57 ). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest trans-eQTL signals in proximal colonic mucosa (e.g. AKAP14, beta=0.61, P=5.02x10-5 ) and opposite signals in distal mucosa (AKAP14, beta=-0.17, P=0.04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa. Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes. This article is protected by copyright. All rights reserved.

Targeted surveillance strategies following initial primary lung cancer (IPLC) treatment are currently limited. One hundred twenty patients diagnosed with IPLC who did not develop second primary lung cancer (SPLC) were matched to 121 patients who developed SPLC. Our analysis found IPLC surgical resection increases SPLC emergence risk regardless of procedure type. Increased survival after IPLC resection warrants close SPLC monitoring. Background: Increased patient survivorship following initial primary lung cancer (IPLC) diagnosis and treatment has uncovered new clinical challenges as individuals post-IPLC are at growing subsequent risk of developing second primary lung cancer (SPLC). Proper SPLC surveillance guidelines aimed at monitoring IPLC survivors are crucial to enhancing health outcomes. This study aims to categorize risk factors associated with SPLC emergence in IPLC survivors for clinical use following IPLC treatment. Materials and Methods: Using the Karmanos Cancer Institute Tumor Registry, patients diagnosed with IPLC from 2000 to 2017 were identified. Patients diagnosed with SPLC were matched to individuals who did not develop SPLC. Logistic and Cox regression analyses were performed to identify risk factors for SPLC emergence and overall survival (OS). Results: One hundred twenty-one patients diagnosed with IPLC who later developed SPLC were identified and compared with 120 patients with IPLC who did not develop SPLC. Several factors such as stage at first diagnosis, histology, age, and smoking history were not associated with SPLC risk. The median time to SPLC was 1.79 years. Patients who were treated with surgical resection had a significantly higher probability of developing SPLC. After correcting for potential immortal time bias, the median OS was 3.63 years (95% confidence interval [CI], 3.05–5.00) and 7.31 years (95% CI, 4.62–10.90) for SPLC and no SPLC groups, respectively. Conclusion: This study uncovered notable associations and lack thereof between several competing SPLC risk factors, as well as mortality. Further characterization of SPLC risk factors is essential for enhancing surveillance recommendations.

Nickel nanoparticles (Ni-NPs) have potential applications in high-tech sectors such as battery manufacturing, catalysis, nanotube printing and textile. Apart from their increasing utilisation in daily life, there are concerns about their hazardous nature as they are highly penetrable in biological systems. The carcinogenic and mutagenic ability of Ni-NPs is evident but the research gaps are still there concerning the safety evaluation of Ni-NPs regarding male reproductive ability. This controlled randomized research was planned to assess the male reproductive toxicity of Ni-NPs in Sprague Dawley rats. Ni-NPs of spherical shape and mean particle size of 56 nm were used in the study, characterized by SEM, EDS and XRD. The twenty-five healthy rats (200-220 g) were used for toxicity investigation of Ni-NPs and divided into five groups; negative control (0 Ni-NPs), placebo group (0.9% saline) and three Ni-NPs treated groups (@ 15, 30 and 45 mg/kg BW). The results of 14 days of intraperitoneal exposure to Ni-NPs revealed that a higher dose (45 mg/kg BW) of Ni-NPs caused a significant reduction in body weight, serum testosterone, daily sperm production while the testis index and Ni accumulation and histological changes (necrosis in basement membrane and seminiferous tubules, vacuole formation) in testicular tissues increased with increasing dose of Ni-NPs. It can be concluded from the study that Ni-NPs have potential reproductive toxicity. This study provided the baseline data of Ni-NPs toxicity for the male reproductive system and can be applied for risk assessment in Ni-NPs based products.

Background We evaluated short- and mid-term outcomes with use of aortic valve-sparing root replacement to treat bicuspid aortic valves. Methods From December 2007 to January 2022, all patients with bicuspid aortic valves who underwent aortic root replacement using Tirone’s procedure were included. This study based on department database information for retrospective and follow-up data. Results Among 51 adults undergoing aortic root replacement using Tirone’s procedure, the mean age was 47.4±12.5 years, and most were men (92.2%). Three presented with a dysmorphic syndrome and one had Marfan’s syndrome. All patients were alive at 30 days, and as of January 2022, 45 were alive, two were lost to follow-up, and there were four noncardiac deaths. Two patients had infectious endocarditis and needed a Bentall’s procedure. One patient had a double biologic valve replacement in the context of severe mitral insufficiency with moderate aortic stenosis at 4.5 years post-procedure. Echocardiographic follow-up showed a left ventricular ejection fraction of 63±7% (n=36), V 2±0.6 m/s (n=17), and a mean gradient of 9.4±5.4 mmHg (n=27). No patients had grade 3 or 4 aortic regurgitation, one patient had grade 2, and four had grade 1. Conclusion Tirone’s procedure is an option for bicuspid aortic valve surgery, with good safety and outcomes, especially in younger patients.

Objectives Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for unachieved cholesterol levels in a real-life APS population. Methods Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination. Cholesterol level targets for each patient were defined according to 2019 ESC/EAS guidelines for the management of dyslipidemia. Results Between January 2020 and April 2021, 114 APS patients were included (male 37 (32.5%); mean age 49 ± 14 years). Among them, 40 (35.1%) had a history of dyslipidemia, 48 (42.1%) were under lipid-lowering therapies, and 59 (51.8%) had a history of cardiovascular disease (CVD). Mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride were, respectively, 110 ± 40 mg/dL, 60±20 mg/dL, and 120 (80–190) mg/dL. Unachieved LDL-C levels were found in 77 (67.5%) patients of whom 53 had history of CVD. Overall, 90 (78.9%) had protective HDL-C and 31 (27.2%) had hypertriglyceridemia. In the multivariate analysis, independent risk factors for unachieved LDL-C levels were older age and history of CVD; triple aPL negativity, defined as complete disappearance of aPL over time in APS patients who were previously positive in accordance to international criteria, was an independent protective factor for unachieved LDL-C. Conclusion Our finding suggested that dyslipidemia is frequent in APS patients and mainly insufficiently treated, especially in patients with history of CVD, who are at highest risk of future CV events.

Background: The COVID-19 pandemic is a viral infection that spreads through different mediums and has a high rate of mortality. At its initial stages, there is no particular medicine that can cure patients of COVID -19. The aim of the present study was to understand the COVID-19 knowledge, perception, and its effects in terms of anxiety and depression among frontline health care workers of Ayub Teaching Hospital, Abbottabad. Methods: This cross-sectional study was conducted in Ayub Teaching Hospital, Abbottabad from June 2021 to Jul 2021 in which data was collected from 200 hospital healthcare workers who have performed duties in COVID isolation wards through standard questionnaire. SPSS version 24.0 was used for data analysis. Results: Out of 200 participants in the study 100 (50.0%) were male. Regarding safety measures taken during COVID -19, 144(72.0%) individuals reported that they have not been given training to handle known or suspected cases of COVID -19. Moderate anxiety and depression was found in 153 (76.5%) healthcare workers, mild in 25 (12.5%) and 22(11.0%) had severe anxiety and depression at the time of COVID -19 pandemic. Conclusion: This study revealed that a significant anxiety and depression was found in frontline healthcare workers during the COVID-19 pandemic. In addition, a more extensive study should be conducted which involves many other hospitals like Ayub Teaching Hospital.

Objective To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. Methods A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. Results The median of age [14 (10–18) vs. 15 (10–18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091–3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001–1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206–0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981–0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. Conclusion Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

The DNA demethylating agent 5-aza-2′-deoxycytidine (DAC, decitabine) has anti-cancer therapeutic potential, but its clinical efficacy is hindered by DNA damage-related side effects and its use in solid tumours is debated. Here we describe how paracetamol augments the effects of DAC on cancer cell proliferation and differentiation, without enhancing DNA damage. Firstly, DAC specifically upregulates cyclooxygenase-2-prostaglandin E2 pathway, inadvertently providing cancer cells with survival potential, while the addition of paracetamol offsets this effect. Secondly, in the presence of paracetamol, DAC treatment leads to glutathione depletion and finally to accumulation of ROS and/or mitochondrial superoxide, both of which have the potential to restrict tumour growth. The benefits of combined treatment are demonstrated here in head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukaemia cell lines, further corroborated in a HNSCC xenograft mouse model and through mining of publicly available DAC and paracetamol responses. The sensitizing effect of paracetamol supplementation is specific to DAC but not its analogue 5-azacitidine. In summary, the addition of paracetamol could allow for DAC dose reduction, widening its clinical usability and providing a strong rationale for consideration in cancer therapy., Highlights • Paracetamol works in synergy with DAC (decitabine) to reduce cancer cell viability. • The synergistic effect is specific for decitabine and not observed for 5-azacitidine. • Paracetamol allows for DAC dose reduction without inducing DNA damage. • Paracetamol counteracts DAC-triggered activation of COX-2-PGE2 pathway. • In the presence of paracetamol DAC induces mimicry of paracetamol overdose leading to oxidative stress.

Sajjad Ahmad,1 Mater H Mahnashi,2 Bandar A Alyami,2 Yahya S Alqahtani,2 Farhat Ullah,1 Muhammad Ayaz,1 Muhammad Tariq,3 Abdul Sadiq,1 Umer Rashid4 1Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia; 3Department PCB, Rokhan University, Jalalabad, Nangrahar, Afghanistan; 4Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanCorrespondence: Abdul SadiqDepartment of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), Khyber Pakhtunkhwa, PakistanTel +92 301 2297 102Email sadiquom@yahoo.comUmer RashidDepartment of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanTel +92-334 5171999Email umerrashid@cuiatd.edu.pkBackground: Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-β-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition.Methods: The compounds (4, 9– 11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target.Results: Four Michael adducts (4, 9– 11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC50 values of 128 and 65 μM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC50 value of 5.79 μM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions.Conclusion: Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.Keywords: Michael products, succinimides, cyclooxygenase, lipoxygenase, analgesic, molecular docking, adrenergic and dopaminergic

Previous studies using additive genetic models failed to identify robust evidence of associations between colorectal cancer (CRC) risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive. Here, we tested all currently known CRC-risk variants (n = 129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were then validated in 2474 CRC cases from UK Biobank. We found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR = 1.97, 95% CI = 1.41-2.74, P = 6.1x10-5 ) and validation analysis (HR = 1.69, 95% CI = 1.03-2.79, P = 0.038). In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR = 1.24, 95% CI = 1.10-1.39, P = 3.4x10-4 ) and CRC-specific survival in the validation cohort (HR = 1.26, 95% CI = 1.01-1.56, P = 0.040). Our findings show that common genetic risk factors can also influence CRC survival outcome. This article is protected by copyright. All rights reserved.

BACKGROUND: We sought to describe characteristics, multisystem outcomes, and predictors of mortality of the critically ill COVID-19 patients in the largest hospital in Massachusetts. METHODS: This is a prospective cohort study. All patients admitted to the intensive care unit (ICU) with reverse-transcriptase-polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 14, 2020, and April 28, 2020, were included; hospital and multisystem outcomes were evaluated. Data were collected from electronic records. Acute respiratory distress syndrome (ARDS) was defined as PaO2/FiO2 ratio of ≤300 during admission and bilateral radiographic pulmonary opacities. Multivariable logistic regression analyses adjusting for available confounders were performed to identify predictors of mortality. RESULTS: A total of 235 patients were included. The median (interquartile range [IQR]) Sequential Organ Failure Assessment score was 5 (3-8), and the median (IQR) PaO2/FiO2 was 208 (146-300) with 86.4% of patients meeting criteria for ARDS. The median (IQR) follow-up was 92 (86-99) days, and the median ICU length of stay was 16 (8-25) days; 62.1% of patients were proned, 49.8% required neuromuscular blockade, and 3.4% required extracorporeal membrane oxygenation. The most common complications were shock (88.9%), acute kidney injury (AKI) (69.8%), secondary bacterial pneumonia (70.6%), and pressure ulcers (51.1%). As of July 8, 2020, 175 patients (74.5%) were discharged alive (61.7% to skilled nursing or rehabilitation facility), 58 (24.7%) died in the hospital, and only 2 patients were still hospitalized, but out of the ICU. Age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12), higher median Sequential Organ Failure Assessment score at ICU admission (OR, 1.24; 95% CI, 1.06-1.43), elevated creatine kinase of ≥1,000 U/L at hospital admission (OR, 6.64; 95% CI, 1.51-29.17), and severe ARDS (OR, 5.24; 95% CI, 1.18-23.29) independently predicted hospital mortality.Comorbidities, steroids, and hydroxychloroquine treatment did not predict mortality. CONCLUSION: We present here the outcomes of critically ill patients with COVID-19. Age, acuity of disease, and severe ARDS predicted mortality rather than comorbidities. LEVEL OF EVIDENCE: Prognostic, level III.

Background The purpose of the study was to evaluate the incidence of postdural puncture headache in a predominantly pediatric sample before and after a transition from conventional to atraumatic spinal needles. Methods In this retrospective cohort study, we analyzed data from 1059 lumbar puncture procedures in 181 individuals enrolled in NIH Clinical Center research protocols. Multivariate logistic regression was used to evaluate the association between postdural puncture headache and spinal needle type after adjusting for patient age, sex, and body mass index. A random effect of participant was used to accommodate repeated observations. Results The median age at time of procedure was 15.3 years. The overall rate of postdural puncture headache was 5.1% (54 of 1059). With conventional needles and atraumatic needles, respectively, the rate of postdural puncture headache was 7.7% (43 of 588) and 2.3% (11 of 471); (odds ratio 0.32, 95% confidence interval 0.15 to 0.68). Conclusions Lumbar puncture for cerebrospinal fluid collection is an essential and common procedure in pediatric clinical care and research. Postdural puncture headache is the most common adverse event of the lumbar puncture procedure. Our data indicate that lumbar puncture is safe in pediatrics and that use of an atraumatic spinal needle further reduces the risk of postdural puncture headache.

BACKGROUND. Patients with acute type A aortic dissection with a previous cardiac surgery (PCS) and malperfusion syndrome (MPS) are extremely difficult to manage and have poor outcomes. METHODS. From 1996 to 2018, 668 patients underwent emergent open aortic repair or endovascular fenestration/stenting for MPS for an acute type A aortic dissection, including those with PCS (PCS, n = 64) and those without PCS (No-PCS, n = 604). The groups were further divided into PCS+MPS, PCS+No-MPS, No-PCS+MPS, and No-PCS+No-MPS. RESULTS. Compared with the No-PCS group, the PCS group had significantly more coronary artery disease, acute renal failure, and mesenteric and renal MPS. Forty-two percent of patients with PCS underwent upfront endovascular fenestration/stenting for endovascular-amendable MPS. The in-hospital mortality was significantly higher in patients with PCS+MPS (40%) compared with PCS+No-MPS (5.9%), No-PCS+MPS (30%) and No-PCS+No-MPS (6.7%). Multivariable logistic regression showed cardiogenic shock (odds ratio, 7.3) and MPS (odds ratio, 6.6) were risk factors for in-hospital mortality (P < .0001). After recovering from MPS the PCS group (n = 54) had similar rates of postoperative complications, including 30-day mortality (7.4% vs 6.3%, P = .77), compared with the No-PCS group (n = 557). The 5-year survival was significantly lower in the PCS group compared with the No-PCS group (60% vs 72%, P = .004) and was lowest in those with PCS+MPS (46%). PCS was not a significant risk factor for in-hospital (odds ratio, 1.2; P = .63) or late (hazard ratio, 1.3; P = .27) mortality. CONCLUSIONS. Because of severe preoperative comorbidities and the complexity of open aortic repair, in acute type A aortic dissection patients with PCS and MPS, endovascular fenestration and stenting first with delayed redo sternotomy and central aortic repair was a valid approach.

Objectives: To estimate the prevalence of burnout among health care workers (HCWs) who are working in Saudi Arabia during the Coronavirus disease 2019 (COVID-19) pandemic, and explore individual and work-related factors associated with burnout in this population. Methods: In this cross-sectional study conducted between June to August of 2020, we invited HCWs through social channels to complete a questionnaire. The questionnaire inquired about demographics, factors related to burnout, and used the Copenhagen Burnout Inventory scale to indicate burnout. A total of 646 HCWs participated. Results: The mean (SD) age of participants was 34.1 (9.5) years. Sixty-one percent were female. The prevalence of burnout among HCWs was 75%. Significant factors associated with burnout were age, job title, years of experience, increased working hours during the pandemic, average hours of sleep per day, exposure to patients with COVID-19, number of times tested for COVID-19, and perception of being pushed to deal with COVID-19 patients. Conclusion: Health care workers as frontline workers, face great challenges during this pandemic, because of the nature of their work. Efforts should be made to promote psychological resilience for HCWs during pandemics. This study points out the factors that should be invested in and the factors that may not be influential.

We sought to determine the number of cases to achieve competency and proficiency in tubularized incised plate technique for distal hypospadias repair using cumulative sum analysis.From 2001 to 2015 we reviewed all distal tubularized incised plate repairs performed by a single surgeon since independent practice. Data for 450 consecutive cases included age, meatal location, presence of curvature, operative time, occurrence of complications and followup duration. A cumulative sum analysis cohort chart was used to determine trends in complication rate and operative time during the evaluation period. In order to account for surgical experience with time, the highest peak, plateau, and down trends in operative time and complication rate were identified on the plot and set as the transition points between learning (phase 1), competence (phase 2) and proficiency (phase 3).Based on the cumulative sum analysis learning curve, the competence phase with plateau of operative time and complication rate commences beyond the 127th case, and the proficiency phase with notable decline in operative time and complication rate was noted beyond the 234th case. When comparing case characteristics and surgical outcomes between phases and learning curve, the proficiency phase involved younger patients and more severe degree of distal hypospadias being repaired using the tubularized incised plate approach with fewer complications related to meatal stenosis and fewer cosmetic complications.In our study competency in distal hypospadias tubularized incised plate repair was reached beyond the 127th case, while proficiency was attained beyond the 234th case.

Niemann-Pick disease type C (NPC) is a neurodegenerative disease in which mutation of NPC1 or NPC2 gene leads to lysosomal accumulation of unesterified cholesterol and sphingolipids. Diagnosis of NPC disease is challenging due to non-specific early symptoms. Biomarker and genetic tests are used as first-line diagnostic tests for NPC. In this study, we developed a plasma test based on N-(3β,5α,6β-trihydroxy-cholan-24-oyl)glycine (TCG) that was markedly increased in the plasma of human NPC1 subjects. The test showed sensitivity of 0.9945 and specificity of 0.9982 to differentiate individuals with NPC1 from NPC1 carriers and controls. Compared to other commonly used biomarkers, cholestane-3β,5α,6β-triol (C-triol) and N-palmitoyl-O-phosphocholine (PPCS, also referred to as lysoSM-509), TCG was equally sensitive for identifying NPC1 but more specific. Unlike C-triol and PPCS, TCG showed excellent stability and no spurious generation of marker in the sample preparation or aging of samples. TCG was also elevated in lysosomal acid lipase deficiency (LALD) and acid sphingomyelinase deficiency (ASMD). Plasma TCG was significantly reduced after intravenous (IV) 2-hydroxypropyl-β-cyclodextrin (HPβCD) treatment. These results demonstrate that plasma TCG was superior to C-triol and PPCS as NPC1 diagnostic biomarker and was able to evaluate the peripheral treatment efficacy of IV HPβCD treatment.

INTRODUCTION Epidemiologic studies have found low/absence of atopy in obese asthmatic children, but the association or lack thereof of atopy with disease morbidity, including pulmonary function, in obese asthma is not well understood. We sought to define the association of atopy with pulmonary function in overweight/obese minority children with asthma. METHODS In a retrospective chart review of 200 predominantly minority children evaluated at an academic Pediatric Asthma Center over 5 years, we compared the prevalence of atopy, defined as ≥ 1 positive skin prick test or serum-specific immunoglobulin E quantification to environmental allergens, and its association with pulmonary function in overweight/obese (body mass index [BMI] > 85th percentile) (n = 99) to healthy-weight children (BMI, 5th-85th percentile for age) (n = 101). RESULTS In a cohort comprised of 47.5% Hispanics and 39.5% African Americans, 81% of overweight/obese and 74% of healthy-weight children were atopic. While atopic healthy-weight children had lower percent-predicted forced expiratory volume in the first second (FEV1 ) (93 ± 13.6 vs 107% ± 33.2%, P = .03) and lower percent-predicted forced vital capacity (FVC) (93% ± 12.2% vs 104% ± 16.1%, P = .01) as compared to nonatopic children, atopy was not associated with FEV1 (P = .7) or FVC (P = .17) in overweight/obese children. Adjusting for demographic and clinical variables, atopy was found to be an independent predictor of FEV1 and FVC in healthy-weight (β = -2.4, P = .07 and β = -1.7, P = .04, respectively) but not in overweight/obese children (β = .6, P = .5 and β = .8, P = .3). CONCLUSIONS Atopy is associated with lower lung function in healthy-weight asthmatics but not in overweight/obese asthmatics, supporting the role of nonallergic mechanisms in disease burden in pediatric obesity-related asthma.

Objective This study was aimed to determine and compare the frequency of the emotional disturbances, anxiety and depression among the medical students on Hospital Anxiety Depression scale (HAD) score among the hostelites and day scholars. Methods This cross sectional study was conducted at a private medical college in Faisalabad, Pakistan, from March 2019 to April 2019, comprising of 105 male and female students. Validated Hospital Anxiety depression scale (HAD-A and HAD-D) was used to collect data from 1st year and 2nd year MBBS students in order to evaluate anxiety and depression among them. Data was analyzed on SPSS 21. Pearson's Chi-square was applied to compare the percentages of anxious and depressed subjects among the studied group. Independent sample t-test was applied for comparison of mean HAD scores between hostelites and day scholars. P value ≤ 0.05 was taken as significant. Results There were 105 students in the study with a mean age of 19.4±0.68 years. Overall, 82.7% students had anxiety, and 52.1% suffered from depression. Average HAD -A and HAD- D scores were 11.2±3.41 and 7.2±3.37 respectively. Greater number of hostelites was suffering from emotional disturbances as compared to day scholars. HAD -A scores was significantly higher in hostelites than day scholars with P value 0.003*(11.85±3.42 Vs 10.92 ±2.56). HAD- D scores were also higher in hostilities but difference was insignificant. (7.57±3.42 Vs 6.85 ±1.58). Conclusions Emotional disturbance including anxiety and depression are found to be highly prevalent among medical students of a private medical college in Faisalabad. Hostelites are more prone to anxiety and depression than day scholars.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint., In this clinical trial, patients with resectable early stage non‐small cell lung cancer received a combination of neoadjuvant chemotherapy with avelumab, an anti‐PD‐L1 monoclonal antibody. The study found that there were no increased surgical complications. Also, the benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Introduction: Percutaneous left atrial appendage closure is an established alternative to anticoagulation therapy for stroke prophylaxis among patients with nonvalvular atrial fibrillation. There are currently no guidelines on the choice of antithrombotic therapy following placement of the Watchman® device, the optimal time to discontinue anticoagulation or the duration of follow-up imaging after device deployment. Our main objective was to evaluate clinical outcomes among these patients. Methods: We conducted a retrospective review of patients who received a Watchman® device at Mayo Clinic sites between January 2010 and December 2018. We constructed Cox-proportional hazard models to evaluate the effect of specific variables on clinical outcomes. Results: 231 patients were identified (33% female), median age was 77 years, CHA2DS2-VASc score was 5 and HASBLED score was 4. We found no difference in clinically significant bleeding based on initial antithrombotic choice. However, patients with prior gastrointestinal bleeding were more likely to have a bleeding event in the first 6 weeks following Watchman® implantation (HR 9.40, 95% CI 2.15–41.09). Device sizes of 24–27 mm were significantly associated with a decreased risk of thromboembolic events (HR 0.15, 95% CI 0.04–0.55) compared to 21-mm devices. Peridevice leak (PDL) sizes appeared to either remain the same or increase on follow-up imaging. Discussion/Conclusions: This observational study showed no statistically significant difference in bleeding risk related to initial antithrombotic choice. Smaller device sizes were associated with thromboembolic events, and longitudinal PDL assessment using transesophageal echocardiography showed these frequently do not decrease in size. Larger studies are needed.

The longevity of a stentless valve in a younger population (20-60 years old) is unknown.From 1992 to 2015, 1947 patients underwent aortic valve/root replacement for aortic stenosis, insufficiency, root aneurysm, or aortic dissection with stentless bioprostheses (median size, 26 mm). At operation 105 patients were40 years old, 528 were 40 to 59, 860 were 60 to 74, and 454 were ≥75 years. The data were obtained through chart review, administered surveys, and the National Death Index.The 30-day mortality rate was 2.6%. During follow-up 807 patients (41%) died before reoperation, 993 (51%) were alive without reoperations because of deterioration, and 113 patients (5.8%) underwent reoperation for structural valve deterioration. After adjusting death and reoperation for non-structural valve deterioration causes as competing risks, the cumulative incidence of reoperation was significantly different between the younger groups (40, 40-59) and the older groups (60-74, ≥75; P.0001) but not inside the younger (40 vs 40-59) or older (60-74 vs ≥75) group. The significant hazard ratio of reoperation for40 versus ≥75 years of age was 12,40 versus 60 to 74 was 4, 40 to 59 versus 60 to 74 was 3, and 40 to 59 versus ≥75 was 9 (P ≤ .01). The 10- and 15-year survival in the entire cohort was 53% and 29%, respectively.The stentless aortic valve provides satisfactory durability as a conduit for aortic valve/root replacement for patients who prefer a bioprosthesis. However it should be judiciously considered for patients younger than 60 years because of an increased incidence of reoperation for structural valve deterioration.

Motivational characteristics such as excitement-seeking are key components of models of addiction, including problem gambling. Previous studies have established associations between excitement-seeking and problem gambling in youth. However, these studies have employed dimensional psychological assessments which are unlikely to be routinely administered. Other approaches to conceptualize excitement-seeking could be of value. In the present study, we employed a single question (What are the reasons that you gamble?) to identify adolescents who reported excitement-seeking motivation for gambling. Cross-sectional data from 2030 adolescent gamblers who participated in a Connecticut high-school survey were examined. Gambling perceptions and correlates of problem-gambling severity were examined relative to excitement-seeking and non-excitement-seeking gambling. Gambling perceptions were more permissive and at-risk/problem gambling was more frequent among adolescents with excitement-seeking gambling versus non-excitement-seeking gambling. A weaker relationship between problem-gambling severity and moderate and heavy alcohol use was observed for excitement-seeking versus non-excitement-seeking gambling. Excitement-seeking gambling is associated with more permissive gambling-related attitudes and riskier gambling behaviors and may account for some variance in adolescent risk of heavy alcohol use. A single question may provide important information for identifying adolescents who are at elevated risk of problem gambling and associated negative outcomes, although the utility of the question in specific settings warrants direct examination, especially given the observed high prevalence of excitement-seeking motivations for gambling.