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Clinical rationale for study: Despite advancements in critical care, the mortality rate of sepsis remains high, with an overall poor prognosis. There is a complex pathophysiology of a lethal cascade of cytokines and inflammatory proteins underlying sepsis. The use of vitamin C can theoretically suppress the inflammatory cascade but remains a questionable practice due to a lack of conclusive evidence. Aims of the study: To appraise the therapeutic role of vitamin C in sepsis. Materials and methods: A systematic review was conducted on PubMed, Embase, and the Central Cochrane Registry. The study included randomized clinical trials (RCTs) with vitamin C as an intervention arm in the septic patient population. For continuous variables, the difference in means (MD) and for discrete variables, the odds ratio (OR) was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. The analysis was performed using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: 23 studies were included with the total sample size of 2712 patients. In patients treated with vitamin C, there was a statistically significant reduction in the mortality: OR = 0.778 (0.635 to 0.954), p = 0.016; the sequential organ failure assessment score (SOFA): MD = −0.749 (−1.115 to −0.383), p < 0.001; and the duration of vasopressor requirement: MD = −1.034 days (−1.622 to −0.445), p = 0.001. No significant difference was found in the hospital or ICU length of stay. Conclusions and clinical implications: Vitamin C treatment regimens were associated with reduced mortality, SOFA score, and vasopressor requirement compared to the control in sepsis. Given its low cost and minimal adverse effects, we strongly encourage further large, randomized trials to establish vitamin C as a standard of care in sepsis management.

Background Normal saline solution (NSS) has been the fluid of choice for renal transplant patients, but it can lead to hyperchloremic acidosis and hyperkalemia. This study was performed to compare the safety profile of low-chloride solutions with that of NSS in renal transplant patients. Methods We conducted a systemic review search on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials (RCTs) and matched cohort studies involving NSS as the control arm and low-chloride solutions as an intervention arm were chosen. The standardized mean difference for continuous variables, the odds ratio (OR) for discrete variables, and a 95% confidence interval (CI) for effect sizes were used. A p-value of

The primary hyperoxalurias are rare disorders of glyoxylate metabolism. Accurate diagnosis is essential for therapeutic and management strategies. We conducted a molecular study on patients suffering from recurrent calcium-oxalate stones and nephrocalcinosis and screened primary hyperoxaluria causing genes in a large cohort of early-onset cases. Disease-associated pathogenic-variants were defined as missense, nonsense, frameshift-indels, and splice-site variants with a reported minor allele frequency1% in controls. We found pathogenic-variants in 34% of the cases. Variants in the AGXT gene causing PH-I were identified in 81% of the mutation positive cases. PH-II-associated variants in the GRHPR gene are found in 15% of the pediatric PH-positive population. Only 3% of the PH-positive cases have pathogenic-variants in the HOGA1 gene, responsible to cause PH-III. A population-specific AGXT gene variant c.1049GA; p.Gly350Asp accounts for 22% of the PH-I-positive patients. Pathogenicity of the identified variants was evaluated by in-silico tools and ACMG guidelines. We have devised a rapid and low-cost approach for the screening of PH by using targeted-NGS highlighting the importance of an accurate and cost-effective screening platform. This is the largest study in Pakistani pediatric patients from South-Asian region that also expands the mutation spectrum of the three known genes.

Case is a morphological realization on a noun phrase (NP) to represent the NP's grammatical relationship with the main verb of the clause. With respect to case, languages, in many cases, can be broadly divided into two alignment systems, i.e., ergative-absolutive and nominative-accusative. In the former type of languages, e.g., Punjabi, the subjects usually receive an ergative post position in transitive clauses (with perfective aspect) while in the latter type of languages, e.g., English, the subject, i.e., in nominative case receives, no post position. There has been a widespread controversy on whether ergative is a structural case or a lexical/inherent case and how the arguments are, i.e., subject and objects valued case in case of ergative clauses. With this ongoing debate in the background, this study aims to compare the marking of case on the arguments, i.e., subjects and objects in the transitive clauses of English and Punjabi. The study is conducted under the minimalist framework of Chomsky (2008), who emphasized on Strong Minimalist Thesis (SMT): language provides the best possible solution to the interface conditions imposed by other systems of the human mind, i.e., related to meaning and sound, which interact with language through their interfaces Conceptual Intentional (C-I) and Sensori-Motor (SM) respectively. In this framework, a feature valuation mechanism is induced by the probes, i.e., C and v*. The study finds that in split ergative languages (the languages which take both case patterns, i.e., nominative and ergative) like Punjabi, the EA, i.e., subjects of perfective transitive clauses are assigned the ergative case by the functional heads v* at [Spec-v*] while the IA, i.e., objects are valued accusative case by the same functional head v* under Agree operation. A consequence of this finding concludes that T has default agreement in such languages, which is possible because Punjabi (like its other South Asian counterparts, e.g., Urdu-Hindi, Bengali, and Kashmiri) is a pro-drop language. So, it is easy to assume that EPP and Agree features of T are an option. Keywords: Case valuation, Strong Minimalist Thesis (SMT), Punjabi, English, ergative, nominative

Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established. To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed. 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

Background: Heart failure with reduced ejection fraction (HFrEF) is associated with recurrent hospitalizations and high mortality. Guideline-directed medical therapy (GDMT) reduces morbidity, mortality and re-admission rates. Despite the evidence, less than 50% of patients with HFrEF are prescribed appropriate medical therapy. When hospitalized patients have these medications discontinued on admission or during hospitalization, they are less likely to have them restarted on discharge. The goal of this study was to determine the incidence of disruption of beta-blocker (BB) therapy during hospitalization for HFrEF patients admitted to an academic tertiary referral hospital. Methods: We conducted a retrospective study in a single teaching hospital over the course of 1 year, and utilized data queried from the electronic medical record (EPIC) database. Inclusion criteria were met by patients with an ICD-10 code diagnosis of heart failure, left ventricular ejection fraction less than 40% and BB prescription prior to admission. Additional information noted included age, sex, vital signs throughout the admission and dates where BB was not given for a full 24-h period. Patients in the intensive care unit (ICU) were excluded due to uncertainty of their hemodynamics. Data were extracted from the electronic medical record database and analyzed through Python, Microsoft Excel and RStudio. The incidence of BB disruption during hospitalization was defined as a 24-h period where no BB was administered. Blood pressure (BP) and heart rate (HR) levels were compared between patients who received BB and patients who had a disruption in their BB. Measurements were also obtained to assess whether a correlation exists between holding BB therapy and time of the year, age, or sex. Results: Between January 2018 and January 2019, 780 patient encounters met inclusion criteria for the study. Patients who were continued on BB therapy had an average BP of 120.8/68.7 mm Hg and an HR of 82.4 bpm on days they received their BB. Patients who had a disruption of BB therapy had an average BP of 117.7/67.6 mm Hg and an HR of 88.6 bpm on the days of the disruption (P < 0.001). There was no association between holding BB and age, sex, or time of year. Conclusions: This study showed that in an academic tertiary referral center, patients with HFrEF who are not in an ICU have a 23% chance of not receiving their recommended BB therapy for 24 h. While the differences measured for BP and HR are statistically significant, they are not clinically significant. Cardiol Res. 2021;12(1):2-9 doi: https://doi.org/10.14740/cr1169

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

Systemic inflammation has long been associated with poor outcomes in many types of solid tumors. Peripheral blood biomarkers, such as absolute lymphocyte count (ALC) and the ratio of absolute neutrophil count to absolute lymphocyte count (ANC/ALC), have been shown to be immune-inflammatory parameters highlighting an individual's immune status. The prognostic role of ALC and ANC/ALC on overall survival (OS) was examined in patients with advanced non-small cell lung carcinoma (NSCLC) receiving pembrolizumab. Of a total of 239 patients, 52% were male, with a median age of 67 years (interquartile range [IQR], 59-73). Most patients had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PD-L1 expression was50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.8 months (IQR, 2.9-12.7). An ANC/ALC5 was associated with improved OS at initiation of pembrolizumab (P = .002), whereas an ALC1.4 deciliter (dL) trended toward improved OS compared with ALC1.4 dL (P = .053). After adjusting for potential cofounders with a multivariate analysis, a baseline ANC/ALC of 5 or higher was associated with a significantly increased risk of death (HR, 1.93; 95% CI, 1.27-2.93; P = .002). An ANC/ALC5 at the time of initiation of treatment with pembrolizumab was associated with improved OS in patients with advanced NSCLC. The median ALC and ANC/ALC were significantly lower after 6 weeks of treatment with pembrolizumab.

Introduction: Magnesium sulfate has been extensively used to treat asthma exacerbations, but its efficacy remains questionable in the chronic obstructive pulmonary disease (COPD) population. The aim of the study was to compare the efficacy of intravenous (IV) magnesium sulfate in COPD. A systemic review search was conducted on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials were included with magnesium sulfate as an intervention arm in the COPD population. Materials and Methods: For continuous variables, standardized mean difference (SMD) and difference in means (MD) were calculated. For discrete variables, the Mantel-Haenszel (MH) odds ratio was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. Analysis was done using both random and fixed effect models. Heterogeneity was evaluated using the I² statistic. Results: Seven studies were included in the final analysis. In patients with acute exacerbations of COPD treated with IV magnesium, a significant increase in forced expiratory volume in one second (FEV₁) was observed (MD = 2.537 [0.717 to 4.357], p = 0.006), as well as in peak expiratory flow rate (PEFR) (SMD = 1.073 [0.748 to 1.397], p < 0.001) using the fixed model. Similarly, residual volume decreased significantly in the IV magnesium group (MD = –0.470 [–0.884 to –0.056], p = 0.026). The hospitalization rate was also lower in the magnesium group, (MH odds ratio 0.453 [0.233 to 0.882], p = 0.020). No statistically significant difference was noted in FEV₁ in the stable COPD population. Conclusion: IV magnesium was associated with a favorable deviation of FEV1 and PEFR, decreased residual volume, and decreased odds of admission in the COPD exacerbation population. Therefore, magnesium sulfate can be used as an adjunctive therapy in the treatment of acute exacerbations of COPD.

Traditionally, normal saline solution (NSS) has been the fluid of choice in diabetic ketoacidosis (DKA) patients, but the NSS is an acidic fluid and may lead to the delayed resolution of DKA. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry to compare the efficacy of low chloride solutions with normal saline solution in DKA resolution. Randomized clinical trials with normal saline as a control arm and low chloride solutions as an intervention arm were included. Four studies were included in the analysis. The investigated outcomes, including time to resolution for DKA and duration of insulin infusion, varied depending on the endpoint were reported in the studies. Overall, balanced solutions were generally associated with faster correction of pH. The time to reach overall DKA endpoints was comparable in both groups. We concluded that crystalloid solutions may be used as an initial resuscitation fluid in the DKA population and may lead to earlier resolution of acidosis. More clinical trial data is required to reach statistical significance for the hypothesis.

Tacrolimus is an immunosuppressive drug widely used in kidney transplantation. Cytochrome P450 3A5 (CYP3A5) protein is involved in tacrolimus metabolism. Single nucleotide polymorphism in the CYP3A5 gene (6986A>G) results in alteration in metabolic activity of CYP3A5 protein which eventually affects the tacrolimus concentration. Patients with CYP3A5 expresser genotypes (A/A *1/*1 and A/G *1/*3) metabolize tacrolimus more rapidly than CYP3A5 nonexpressers (G/G *3/*3). We performed meta-analysis to estimate the effect of CYP3A5 polymorphism on the trough concentration–dose ratio (Co/D) and risk of renal allograft rejection with similar post-transplant periods and Asian vs. European populations. Our results showed that the tacrolimus Co/D ratio is significantly lower in CYP3A5 expresser group as compared with nonexpresser in Asian as well as in European populations at any post-transplant period (p

The association between thyroid hormones and cardiovascular conditions has been well studied, specifically, the effects of hypothyroidism on cardiomyopathy, and hyperthyroidism with arrhythmias. Nonetheless, an explicit correlation between hyperthyroidism and cardiomyopathy has yet to be established. Medical databases MEDLINE and PubMed were accessed and queried as primary sources for data acquisition. Search criteria consisted of “hyperthyroidism”, “heart failure”, and “thyroid and cardiovascular system”, which allowed the retrieval of relevant and recent works. From these sources, a consensus was developed and employed to yield an updated review of the etiology of heart failure in the setting of hyperthyroidism. It is rare for patients with hyperthyroidism to remain in a chronic hyperthyroid state, making it difficult to analyze subsequent long-term effects on the cardiovascular system. Related to heart failure, some studies have demonstrated no change in ejection fraction, while others have shown an acute change along with diastolic dysfunction, with or without an underlying rhythm abnormality. Further investigation is warranted to elucidate the mechanism driving such cardiac dysfunction, and whether it is due to vascular changes, tachyarrhythmias, or myocyte remodeling and fibrosis. The intent of this review article is to improve our understanding of how a hyperthyroid state affects cardiovascular function. An enhanced understanding of the effects on cardiovascular physiology will afford physicians the ability to provide more comprehensive care in consideration of both endocrine and cardiovascular pathologies.

In this advance era, smart grid (SG) deployment is a global trend in which demand side management (DSM) have great significance to make the entire network more stable and efficient. SG is a novel form of conventional grid with large number of information and communication technologies. This research deals with the challenge of DSM in SG by implementing the approach of artificial neural network (ANN) to fulfil the demand of customers from average to peak times. There are various topologies are used for DSM discuss in literature, however ANN is more efficient with less response time by informing about energy prediction to providers and consumers which are connected with several clouds. The results shows the prediction of demand from daily to monthly basis by implementing the approach of ANN. The procedure of testing to training of ANN dataset is prepared using the MATLAB software.

COVID-19 displays marked variability in the clinical course as well as regional epidemiology. Abnormalities in RAAS system especially stemming from genetic variability in ACE and ACE2 expression (including ACE I/D polymorphism) have been proposed to explain underlying pathogenesis and variability in SARS-CoV-2 infection. In a meta-regression data set of 30 countries, we found significant associations of ACE I/D ratio and COVID-19 prevalence, deaths and recovery rate but not when adjusted for possible confounders. This ecological study suggests potential of ACE I/D data as predictive biomarker COVID-19 risk and severity in a population specific manner, subject to validation in large genetic epidemiological and functional studies.

Lung cancer is one of the most common cancers diagnosed every year and accounts for a major percentage of cancer incidence and mortality annually, especially in men. Lung adenocarcinoma is a subtype of non-small cell lung cancer (NSCLC), which is the most common type of lung cancer found in smokers and nonsmokers alike. It is known to have diverse CT chest findings ranging from: ground-glass opacities (GGOs) with partially solid nodules, to single or multiple solid nodules that can be either central or peripheral, to thin-walled cystic lesions. Lesions are usually solitary but may be multifocal. Rarely, these lesions can be calcified or demonstrate cavitation, which can make it difficult to distinguish from an infectious disease like tuberculosis, pneumonia, or even fungal infections. Here, we present a case of a 36-year-old Asian male with no significant past medical history, except a 16-pack-year smoking history and recent deployment to Afghanistan, that initially presented with a chief complaint of cough of three-week duration. His CT scan showed innumerable bilateral pulmonary nodules within both lung fields with a miliary type appearance that ultimately turned out to be adenocarcinoma.

Background Urolithiasis is a worldwide urological problem with significant contribution of genetic factors. Pakistan, which resides within the Afro-Asian stone belt, has a high reported prevalence (12%) of urolithiasis. Osteopontin (SPP1) is a urinary macromolecule with a suggested critical role in modulating renal stone formation, genetic polymorphisms of which may determine individual risk of developing urolithiasis. However, results of previous studies regarding SPP1 polymorphisms and susceptibility to urolithiasis have apparent inconsistencies with no data available for local population. Methods A total of 235 urolithiasis patients and 243 healthy controls, all of Pakistani ancestry, underwent genotyping for six SPP1 genetic polymorphisms in an effort to investigate potential association with urolithiasis using indigenous candidate gene association study design. Further, a comprehensive meta-analysis following a systematic literature search was also done to ascertain an evidence based account of any existent association regarding SPP1 promoter polymorphisms and risk of developing urolithiasis. Results Three SPP1 promoter polymorphisms, rs2853744:G > T, rs11730582:T > C and rs11439060:delG>G, were found to be significantly associated with risk of urolithiasis in indigenous genetic association study (OR = 3.14; p = 0.006, OR = 1.78; p = 0.006 and OR = 1.60; p = 0.012, respectively). We also observed a 1.68-fold positive association of a tri-allelic haplotype of these SPP1 promoter polymorphisms (G-C-dG) with risk of urolithiasis (OR = 1.68; p = 0.0079). However, no association was evident when data were stratified according to gender, age at first presentation, stone recurrence, stone multiplicity, parental consanguinity and family history of urolithiasis. The overall results from meta-analysis, which included 4 studies, suggested a significant association of SPP1 rs2853744:G > T polymorphism with susceptibility of urolithiasis (OR = 1.37; p = 0.004), but not for other SPP1 polymorphic variants analyzed. Conclusions In conclusion, we report significant association of 3 SPP1 polymorphisms with urolithiasis for the first time from South Asia, however, this association persisted only for SPP1 rs2853744:G > T polymorphism after meta-analysis of pooled studies. Further studies with a larger sample size will be required to validate this association and assess any potential usefulness in diagnosis and prognosis of renal stone disease.

The term smart grid (SG) allows optimizing energy efficiency by flexible interconnection of central and distributed generators (DG) through transmission and distribution system to industrial and consumer end-users. In near future it is predicted that Distributed Generation (DG) from renewable energy resources (RES) will play a massive role to fulfill the users need and enhance the efficiency of smart grid. The increasing use of switching applications in SG integrated with RES may cause power quality problems in the term of harmonics pollution in the distribution systems. This paper proposes the designing and use of LLCL filter to mitigate the effect of harmonics in smart grids. The performance of the suggested method is checked by the simulation results using ETAP (Electrical Transient and Analyzer Program) and MATLAB (Matrix Laboratory). Theoretical analysis has been done using Simulation and real time data results of Sapphire Textile Industry unit-3.

Angiosarcoma is an aggressive mesenchymal sarcoma of endothelial cell origin with high mortality. Its occurrence in the small intestine is exceedingly low. In addition to the rarity of small intestine angiosarcoma, the nonspecific early clinical symptoms obscure the suspicion of such tumors and thereby delay the diagnosis. In a hope to improve the knowledge of this rare but fatal neoplasm, we report one case of angiosarcoma of duodenum and jejunum in a 73-year-old man. Furthermore, we summarize and analyze the common clinical features, tumor markers, treatment, and survival of previous reported cases of this malignancy. Small bowel angiosarcoma occurs more often in men than women (1.6:1). The median age at diagnosis is 68.5 years. The overall median survival time is 150 days; the median survival time in female (300 days) is longer than that of male patients (120 days). Von Willebrand factor (vWF), CD31, CD34, vimentin, and Ulex europaeus agglutinin 1 appear to be the most useful markers for the diagnosis. The majority of the patients underwent surgical resection alone or surgery with subsequent chemotherapy. The patients treated with surgery plus chemotherapy survive longer than those underwent surgical resection only (median 420 days, n = 7 vs. 96.5 days, n = 26, respectively; P = 0.0275). Further studies of more cases are needed for a better understanding of this rare entity, as well as the development of effective strategies for prevention, early diagnosis, and treatment.