Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Efficacy and Safety of Oral GnRh Antagonists in Patients With Uterine Fibroids: A Systematic Review.

OBJECTIVE: This review aimed to assess the efficacy and safety of GnRH antagonists in patients with symptomatic uterine fibroids. DATA SOURCES: A literature search was performed on PubMed, Web of Science, Embase, Cochrane, and ClinicalTrials.gov using the MeSH and Emtree terms "leiomyoma" and "gonadotropin-releasing hormone." STUDY SELECTION: All clinical trials that provided efficacy and safety data in clinical terms (i.e., reduction in menstrual bleeding and discomfort, changes in the size of leiomyoma and uterine volume, etc.) were included. We excluded all preclinical studies, case reports, meta-analyses, review articles, and clinical studies irrelevant to the study question. DATA EXTRACTION AND SYNTHESIS: Two authors extracted data from 9 clinical studies. The extracted data included the study's characteristics, participants' baseline characteristics, treatment drugs, efficacy measures, and toxicity. CONCLUSION: Among oral GnRH antagonists, relugolix, elagolix, and linzagolix were safe in patients with uterine fibroids. These drugs, alone and in combination with E2/NETA (estradiol/norethindrone acetate), showed significantly better efficacy than placebo in improving bleeding, discomfort, uterine/leiomyoma sizes, and quality of life in premenopausal patients with symptomatic uterine fibroids. However, more randomized, double-blind, multicentre clinical trials are needed to confirm these results and to see long-term benefits.

Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients.

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

Intranasally administered protein coated chitosan nanoparticles encapsulating influenza H9N2 HA2 and M2e mRNA molecules elicit protective immunity against avian influenza viruses in chickens.

Chitosan nanoparticles (CNPs) represent an efficient vaccination tool to deliver immunogenic antigens to the antigen-presenting cells (APCs), which subsequently stimulate protective immune responses against infectious diseases. Herein, we prepared CNPs encapsulating mRNA molecules followed by surface coating with conserved H9N2 HA2 and M2e influenza proteins. We demonstrated that CNPs efficiently delivered mRNA molecules into APCs and had effectively penetrated the mucosal barrier to reach to the immune initiation sites. To investigate the potential of CNPs delivering influenza antigens to stimulate protective immunity, we intranasally vaccinated chickens with empty CNPs, CNPs delivering HA2 and M2e in both mRNA and protein formats (CNPs + RNA + Pr) or CNPs delivering antigens in protein format only (CNPs + Pr). Our results demonstrated that chickens vaccinated with CNPs + RNA + Pr elicited significantly (p < 0.05) higher systemic IgG, mucosal IgA antibody responses and cellular immune responses compared to the CNPs + Pr vaccinated group. Consequently, upon challenge with either H7N9 or H9N2 avian influenza viruses (AIVs), efficient protection, in the context of viral load and lung pathology, was observed in chickens vaccinated with CNPs + RNA + Pr than CNPs + Pr vaccinated group. In conclusion, we show that HA2 and M2e antigens elicited a broad spectrum of protection against AIVs and incorporation of mRNAs in vaccine formulation is an effective strategy to induce superior immune responses.

Oral immunization with an attenuated Salmonella Gallinarum encoding the H9N2 haemagglutinin and M2 ectodomain induces protective immune responses against H9N2 infection in chickens.

H9N2, a low pathogenic avian influenza virus, causes significant economic losses in the poultry industry worldwide. Herein, we describe the construction of an attenuated Salmonella Gallinarum (SG) strain for expression and delivery of H9N2 haemagglutinin (HA) 1 (SG-HA1), HA2 (SG-HA2) and/or the conserved matrix protein 2 ectodomain (SG-M2e). We demonstrated that recombinant SG strains expressing HA1, HA2 and M2e antigens were immunogenic and safe in a chicken model. Chickens (n = 8) were vaccinated once orally with SG alone, SG-HA1, SG-HA2, SG-M2e, or mixture of SG-HA1, SG-HA2 and SG-M2e, or vaccinated once intramuscularly with an oil-adjuvant inactivated H9N2 vaccine. Our results demonstrated that vaccination with SG mutants encoding influenza antigens, administered individually or as a mixture, elicited significantly (P < 0.05) greater antigen-specific humoral and cell-mediated immune responses in chickens compared with those vaccinated with SG alone. A conventional H9N2 vaccine induced significantly (P < 0.05) greater HA1 and HA2 antibody responses than SG-based H9N2 vaccine strains, but significantly (P < 0.05) less robust M2e-specific responses. Upon challenge with the virulent H9N2 virus on day 28 post-vaccination, chickens vaccinated with either the SG-based H9N2 or conventional H9N2 vaccines exhibited comparable lung inflammation and viral loads, although both were significantly lower (P < 0.05) than in the group vaccinated with SG alone. In conclusion, our results showed that SG-based vaccination stimulated efficient immune responses against virulent H9N2. Further studies are needed to fully develop this approach as a preventive strategy for low pathogenic avian influenza viruses affecting poultry. RESEARCH HIGHLIGHTS S. gallinarum expressing HA1, HA2 and M2e antigens are immunogenic and safe. Salmonella has dual function of acting as a delivery system and as a natural adjuvant. Vaccine constructs elicit specific humoral and cell-mediated immune responses.

Salmonella Gallinarum delivering M2eCD40L in protein and DNA formats acts as a bivalent vaccine against fowl typhoid and H9N2 infection in chickens.

Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and H9N2 influenza infection are two economically important diseases that affect poultry industry worldwide. Herein, we exploited a live attenuated SG mutant (JOL967) to deliver highly conserved extracellular domains of H9N2 M2 (M2e) to induce protective immunity against both H9N2 infection and FT. To increase the immunogenicity of M2e, we physically linked it with CD40L and cloned the fusion gene into either prokaryotic constitutive expression vector pJHL65 or mammalian expression vector pcDNA3.1+. Then pJHL65-M2eCD40L or pcDNA-M2eCD40L recombinant plasmid was electroporated into JOL967 strain and the resultant clones were designated as JOL2074 and JOL2076, respectively. We demonstrated that the chickens vaccinated once orally with a co-mix of JOL2074 and JOL2076 strains elicited significantly (p < 0.05) higher M2e-specific humoral and cell-mediated immunity compared to JOL2074 alone vaccinated group. However, SG-specific immune responses were comparable in both the vaccination groups. On challenge with the virulent H9N2 virus (105 TCID50) at 28th day post-vaccination, chickens that received a co-mix of JOL2074 plus JOL2076 strains exhibited significantly (p < 0.05) lower lung inflammation and viral load in both lungs and cloacal samples than JOL2074 alone vaccinated group. Against challenge with the lethal wild-type SG, both the vaccination groups exhibited only 12.5% mortality compared to 75% mortality observed in the control group. In conclusion, we show that SG delivering M2eCD40L can act as a bivalent vaccine against FT and H9N2 infection and further studies are warranted to develop this SG-M2eCD40L vaccine as a broadly protective vaccine against avian influenza virus subtypes.

Oral immunization with a novel attenuated Salmonella Gallinarum encoding infectious bronchitis virus spike protein induces protective immune responses against fowl typhoid and infectious bronchitis in chickens.

Fowl typhoid (FT), a septicemic disease caused by Salmonella Gallinarum (SG), and infectious bronchitis (IB) are two economically important avian diseases that affect poultry industry worldwide. Herein, we exploited a live attenuated SG mutant, JOL967, to deliver spike (S) protein 1 of IB virus (V) to elicit protective immunity against both FT and IB in chickens. The codon optimized S1 nucleotide sequence was cloned in-frame into a prokaryotic constitutive expression vector, pJHL65. Subsequently, empty pJHL65 or recombinant pJHL65-S1 plasmid was electroporated into JOL967 and the resultant clones were designated as JOL2068 and JOL2077, respectively. Our results demonstrated that the chickens vaccinated once orally with JOL2077 elicited significantly (p < 0.05) higher IBV-specific humoral and cell-mediated immunity compared to JOL2068 and PBS control groups. Consequently, on challenge with the virulent IBV strain at 28th day post-vaccination, JOL2077 vaccinated birds displayed significantly (p < 0.05) lower inflammatory lesions in virus-targeted tissues compared to control groups. Furthermore, 33.3% (2 of 6) of birds vaccinated with JOL2077 vaccine had shown virus recovery from tracheal tissues compared to 100% (6 of 6) recovery obtained in both the control groups. Against wild-type SG lethal challenge, both JOL2077 and JOL2068 vaccinated groups exhibited only 10% mortality compared to 80% mortality observed in PBS control group. In conclusion, we show that JOL2077 can induce efficient IBV- and carrier-specific protective immunity and can act as a bivalent vaccine against FT and IB. Further studies are warranted to investigate the potential of JOL2077 vaccine in broiler and young layer birds.

Oral immunization with a novel attenuated Salmonella Typhimurium encoding influenza HA, M2e and NA antigens protects chickens against H7N9 infection.

Attenuated Salmonella strains constitute a promising technology for the development of efficient protein-based influenza vaccines. H7N9, a low pathogenic avian influenza (LPAI) virus, is a major public health concern and currently there are no effective vaccines against this subtype. Herein, we constructed a novel attenuated Salmonella Typhimurium strain for the delivery and expression of H7N9 hemagglutinin (HA), neuraminidase (NA) or the conserved extracellular domain of the matrix protein 2 (M2e). We demonstrated that the constructed Salmonella strains exhibited efficient HA, NA and M2e expressions, respectively, and the constructs were safe and immunogenic in chickens. Our results showed that chickens immunized once orally with Salmonella (Sal) mutants encoding HA (Sal-HA), M2e (Sal-M2e) or NA (Sal-NA), administered either alone or in combination, induced both antigen-specific humoral and cell mediated immune (CMI) responses, and protected chickens against the lethal H7N9 challenge. However, chickens immunized with Sal-HA+Sal-M2e+Sal-NA vaccine constructs exhibited efficient mucosal and CMI responses compared to the chickens that received only Sal-HA, Sal-M2e or Sal-M2e+Sal-NA vaccine. Further, chickens immunized with Sal-HA+Sal-M2e+Sal-NA constructs cleared H7N9 infection at a faster rate compared to the chickens that were vaccinated with Sal-HA, Sal-M2e or Sal-M2e+Sal-NA, as indicated by the reduced viral shedding in cloacal swabs of the immunized chickens. We conclude that this vaccination strategy, based on HA, M2e and NA, stimulated efficient induction of immune protection against the lethal H7N9 LPAI virus and, therefore, further studies are warranted to develop this approach as a potential prophylaxis against LPAI viruses affecting poultry birds.

Development of ssDNA aptamers as potent inhibitors of Mycobacterium tuberculosis acetohydroxyacid synthase.

Acetohydroxyacid synthase (AHAS) from Mycobacterium tuberculosis (Mtb) is a promising potential drug target for an emerging class of new anti-tuberculosis agents. In this study, we identify short (30-mer) single-stranded DNA aptamers as a novel class of potent inhibitors of Mtb-AHAS through an in vitro DNA-SELEX method. Among all tested aptamers, two candidate aptamers (Mtb-Apt1 and Mtb-Apt6) demonstrated the greatest inhibitory potential against Mtb-AHAS activity with IC50 values in the low nanomolar range (28.94±0.002 and 22.35±0.001 nM respectively). Interestingly, inhibition kinetics analysis of these aptamers showed different modes of enzyme inhibition (competitive and mixed type of inhibition respectively). Secondary structure-guided mutational modification analysis of Mtb-Apt1 and Mtb-Apt6 identified the minimal region responsible for their inhibitory action and consequently led to 17-mer and 20-mer shortened aptamers that retained equivalent or greater inhibitory potential. Notably, a modeling and docking exercise investigated the binding site of these two potent inhibitory aptamers on the target protein and showed possible involvement of some key catalytic dimer interface residues of AHAS in the DNA-protein interactions that lead to its potent inhibition. Importantly, these two short candidate aptamers, Mtb-Apt1 (17-mer) and Mtb-Apt6 (20-mer), also demonstrated significant growth inhibition against multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of tuberculosis with very low MIC of 5.36 µg/ml and 6.24 µg/ml, respectively and no significant cytotoxicity against mammalian cell line. This is the first report of functional inhibitory aptamers against Mtb-AHAS and provides the basis for development of these aptamers as novel and strong anti-tuberculosis agents.

Synergistic effect of high-mobility group box-1 and lipopolysaccharide on cytokine induction in bovine peripheral blood mononuclear cells.

High-mobility group box 1 (HMGB1) is one of the potent endogenous adjuvants released by necrotic and activated innate immune cells. HMGB1 modulates innate and adaptive immune responses in humans and mice by mediating immune cells crosstalk. However, the immuno-modulatory effects of HMGB1 in the bovine immune system are not clearly known. In this study, the effect of bovine HMGB1 alone or in combination with LPS on the expression kinetics of cytokines upon in vitro stimulation of bovine peripheral blood mononuclear cells (PBMCs) was investigated by quantitative PCR assay. The biological activity of bovine HMGB1 expressed in this prokaryotic expression system was confirmed by its ability to induce nitric oxide secretion in RAW 264.7 cells. The present results indicate that HMGB1 induces a more delayed TNF-α response than does LPS in stimulated PBMCs. However, IFN-γ, IFN-ß and IL-12 mRNA transcription peaked at 6 hr post stimulation after both treatments. Further, HMGB1 and LPS heterocomplex up-regulated TNF-α, IFN-γ and IL-12 mRNA expression significantly than did individual TLR4 agonists. The heterocomplex also enhanced the expression of TLR4 on bovine PBMCs. In conclusion, the data indicate that HMGB1 and LPS act synergistically and enhance proinflammatory cytokines, thereby eliciting Th1 responses in bovine PBMCs. These results suggest that HMGB1 can act as an adjuvant in modulating the bovine immune system and thus lays a foundation for using HMGB1 as an adjuvant in various bovine vaccine preparations.

Immunological evaluation of mannosylated chitosan nanoparticles based foot and mouth disease virus DNA vaccine, pVAC FMDV VP1-OmpA in guinea pigs.

A DNA vaccine for foot and mouth disease (FMD) based on mannosylated chitosan nanoparticles was evaluated in guinea pigs. The DNA construct was comprised of FMD virus full length-VP1 gene and outer membrane protein A (Omp A) gene of Salmonella typhimurium as a Toll-like receptor (TLR)-ligand in pVAC vector. Groups of guinea pigs immunized either intramuscularly or intra-nasally were evaluated for induction of virus neutralizing antibodies, Th1(IgG2) and Th2 (IgG1) responses, lymphocyte proliferation, reactive nitrogen intermediate production, secretory IgA for naso-mucosal immune response and protection upon homotypic type O virulent FMD virus challenge. The results indicate the synergistic effect of OmpA on the immunogenic potential of FMD DNA vaccine construct delivered using mannosylated chitosan nano-particles by different routes of administration. These observations suggest the substantial improvement in all the immunological parameters with enhanced protection in guinea pigs.

Linking S. aureus Immune Evasion Mechanisms to Staphylococcal Vaccine Failures.

Vaccination arguably remains the only long-term strategy to limit the spread of S. aureus infections and its related antibiotic resistance. To date, however, all staphylococcal vaccines tested in clinical trials have failed. In this review, we propose that the failure of S. aureus vaccines is intricately linked to prior host exposure to S. aureus and the pathogen's capacity to evade adaptive immune defenses. We suggest that non-protective immune imprints created by previous exposure to S. aureus are preferentially recalled by SA vaccines, and IL-10 induced by S. aureus plays a unique role in shaping these non-protective anti-staphylococcal immune responses. We discuss how S. aureus modifies the host immune landscape, which thereby necessitates alternative approaches to develop successful staphylococcal vaccines.

A lightweight and robust authentication scheme for the healthcare system using public cloud server.

Cloud computing is vital in various applications, such as healthcare, transportation, governance, and mobile computing. When using a public cloud server, it is mandatory to be secured from all known threats because a minor attacker's disturbance severely threatens the whole system. A public cloud server is posed with numerous threats; an adversary can easily enter the server to access sensitive information, especially for the healthcare industry, which offers services to patients, researchers, labs, and hospitals in a flexible way with minimal operational costs. It is challenging to make it a reliable system and ensure the privacy and security of a cloud-enabled healthcare system. In this regard, numerous security mechanisms have been proposed in past decades. These protocols either suffer from replay attacks, are completed in three to four round trips or have maximum computation, which means the security doesn't balance with performance. Thus, this work uses a fuzzy extractor method to propose a robust security method for a cloud-enabled healthcare system based on Elliptic Curve Cryptography (ECC). The proposed scheme's security analysis has been examined formally with BAN logic, ROM and ProVerif and informally using pragmatic illustration and different attacks' discussions. The proposed security mechanism is analyzed in terms of communication and computation costs. Upon comparing the proposed protocol with prior work, it has been demonstrated that our scheme is 33.91% better in communication costs and 35.39% superior to its competitors in computation costs.

Efficacy and Safety of Different Dosing Regimens of Rivaroxaban in Patients With Atrial Fibrillation for Stroke Prevention: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) poses a substantial risk of stroke, necessitating effective anticoagulation therapy. This systematic review and meta-analysis (SRMA) evaluates the efficacy and safety of different dosing regimens of rivaroxaban in patients with AF. A comprehensive search of relevant databases, focusing on studies published from 2017 onward, was conducted. Inclusion criteria comprised randomized controlled trials (RCTs) and observational studies comparing standard and reduced dosing of rivaroxaban in AF. Data extraction and risk of bias (ROB) assessment were performed, and a meta-analysis was conducted for relevant outcomes. A total of 21 studies fulfilled the inclusion criteria. Standard dosing demonstrates a slightly lower risk of composite effectiveness outcomes and safety outcomes (HR: 0.79, 95% CI: 0.66-0.94, P=0.01) compared to reduced dosing (HR: 0.83, 95% CI: 0.71-0.97, P=0.02). Notable differences in major bleeding, gastrointestinal bleeding (GIB), and intracranial bleeding favored standard dosing. Hemorrhagic stroke and all-cause stroke rates differed significantly, with standard dosing showing a more favorable profile for ischemic stroke prevention. This study highlights the pivotal role of personalized anticoagulation therapy in AF. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines. The study bridges evidence from clinical trials to real-world practice, offering insights into the evolving landscape of AF management.

Experiences of Healthcare Workers in Long-Term Care during COVID-19: A Scoping Review.

Background: Although healthcare workers (HCWs) in long-term care (LTC) have experienced significant emotional and psychological distress throughout the pandemic, little is known about their unique experiences. Objective: This scoping review synthesizes existing research on the experiences of HCWs in LTC during the COVID-19 pandemic. Method: Following Arksey and O'Malley's framework, data published between March 2020 to June 2022, were extracted from six databases. Results: Among 3808 articles screened, 40 articles were included in the final analysis. Analyses revealed three interrelated themes: carrying the load (moral distress); building pressure and burning out (emotional exhaustion); and working through it (a sense of duty to care). Conclusion: Given the impacts of the pandemic on both HCW wellbeing and patient care, every effort must be made to address the LTC workforce crisis and evaluate best practices for supporting HCWs experiencing mental health concerns during and post-COVID-19.

The complexity of examining laboratory-based biological markers associated with mortality in hospitalized patients during early phase of the COVID-19 pandemic: A systematic review and evidence map.

IMPORTANCE: The measurement of laboratory biomarkers plays a critical role in managing patients with COVID-19. However, to date most systematic reviews examining the association between laboratory biomarkers and mortality in hospitalized patients early in the pandemic focused on small sets of biomarkers, did not account for multiple studies including patients within the same institutions during overlapping timeframes, and did not include a significant number of studies conducted in countries other than China. OBJECTIVE: To provide a comprehensive summary and an evidence map examining the relationship between a wide range of laboratory biomarkers and mortality among patients hospitalized with COVID-19 during the early phase of the pandemic in multiple countries. EVIDENCE REVIEW: MEDLINE, EMBASE, and Web of Science were searched from Dec 2019 to March 9, 2021. A total of 14,049 studies were identified and screened independently by two raters; data was extracted by a single rater and verified by a second. Quality was assessed using the Joanna Briggs Institute (JBI) Case Series Critical Appraisal tool. To allow comparison across biomarkers, standardized mean differences (SMD) were used to quantify the relationship between laboratory biomarkers and hospital mortality. Meta-regression was conducted to account for clustering within institutions and countries. RESULTS: Our systematic review included 94 case-series studies from 30 countries. Across all biomarkers, the largest and most precise SMDs were observed for cardiac (troponin (1.03 (95% CI 0.86 to 1.21)), and BNP/NT-proBNP (0.93 (0.52 to 1.34)), inflammatory (IL-6 (0.97 (0.67 to 1.28) and Neutrophil-to-lymphocyte ratio (0.94 (0.59 to 1.29)), and renal biomarkers (blood urea nitrogen (1.01 (0.79 to 1.23)) and estimated glomerular filtration rate (-0.96 (-1.42 to -0.50)). There was heterogeneity for most biomarkers across countries with studies conducted in China generally having larger effect sizes. CONCLUSIONS AND RELEVANCE: The results of this study provide an early pandemic summary of the relationship between biomarkers and mortality in hospitalized patients. We found our estimated ESs were generally attenuated compared to previous systematic reviews which predominantly included studies conducted in China. Despite using sophisticated methodology to examine studies across countries, heterogeneity in reporting of case-series studies early in the pandemic limits clinical interpretability.

Prevalence of peripheral arterial disease in type 2 diabetics in Pakistan.

OBJECTIVES: To observe the prevalence of peripheral arterial disease (PAD) and associated factors among people with type 2 diabetes in Pakistan. METHODS: A multicenter cross-sectional study was carried out at eight centers in all the provinces of Pakistan on people with type 2 diabetes. History of symptoms related to Peripheral arterial disease were noted and anthropometric measurements were recorded. Ankle brachial index (ABI) was measured using Doppler ultrasound; patients with ABI < 0.9 were classified as having low ABI. RESULTS: There were 830 patients in the study, (49% males and 51% females). Females were younger and had a higher body mass index (BMI) (p < 0.001). The prevalence of peripheral arterial disease was 31.6% with a 95% CI of 28.4% to 34.8%. There was no significant difference in the proportion of low ABI between males (30%) and females (33%) (p = 0.29). Patients with low ABI were found to have significantly higher BMI (p = 0.02) and waist circumference (p = 0.001). The most common symptom in the patients with low ABI was pain on walking (84%), followed by numbness of the feet (64%). There was a significant difference in the reporting of all the symptoms (p < 0.05) except for numbness of the feet (p = 0.57) as compared to patients with normal ABI. No association was found between low ABI and duration of diabetes mellitus or cigarette smoking. There was no significant association between cardiovascular conditions and low ABI. CONCLUSION: Peripheral arterial disease is common among people with type 2 diabetes in Pakistan and needs to be properly evaluated by the medical professionals as early diagnosis can help prevent future complications.

"Fish Gill" Incisions for Severe Periorbital Surgical Emphysema Following Tension Pneumothorax - A Case Report and Review of the Literature.

BACKGROUND: Surgical emphysema refers to the presence of air within the subcutaneous space and is a known complication of chest drain insertion. Symptoms range from mild crepitus of the chest wall to the accumulation of air in the face and neck, which can ultimately result in cardiovascular compromise. OBJECTIVE: The aim of this article is to present a rare case of cervical, facial and periorbital surgical emphysema following chest drain insertion, and describes a novel use of 'fish gill' incisions in the palpebromalar groove with an associated review of the literature. CASE REPORT: A 68-year-old gentleman presented with acute dyspnoea due to a right-sided tension pneumothorax. Emergency decompression with a Seldinger chest drain resulted in persistent cervical, facial and periorbital surgical emphysema causing difficulty in movement, inability to open the eyes and progressive risk to cervical venous return. "Fish gill' incisions at the lateral-most edge of the palpebromalar groove, down to the level of the orbicularis oculi muscle, rapidly released air from the face and neck, alleviating discomfort, reducing venous compression and restoring vision. CONCLUSION: Cervical, fascial and periorbital surgical emphysema may be resolved with the use of "fish gill" incisions at the lateral palpebromalar groove and simple drains. To the best of our knowledge, this method has not been reported previously in the literature.

Anti-Inflammatory Properties of Plasma from Children with Short Bowel Syndrome.

Sepsis, resulting from a dysregulated host immune response to invading pathogens, is the leading cause of mortality in critically ill patients worldwide. Immunomodulatory treatment for sepsis is currently lacking. Children with short bowel syndrome (SBS) may present with less severe symptoms during gram-negative bacteremia. We, therefore, tested the hypothesis that plasma from children with SBS could confer protection against Escherichia coli sepsis. We showed that SBS plasma at 5% and 10% concentrations significantly (p < 0.05) inhibited the production of both TNF-α and IL-6 induced by either E. coli- or LPS-stimulated host cells when compared to plasma from healthy controls. Furthermore, mice treated intravenously with select plasma samples from SBS or healthy subjects had reduced proinflammatory cytokine levels in plasma and a significant survival advantage after E. coli infection. However, SBS plasma was not more protective than the plasma of healthy subjects, suggesting that children with SBS have other immunomodulatory mechanisms, in addition to neutralizing antibodies, to alleviate their symptoms during gram-negative sepsis.

Secure Patient Authentication Framework in the Healthcare System Using Wireless Medical Sensor Networks.

Biosensor is a means to transmit some physical phenomena, like body temperature, pulse, respiratory rate, electroencephalogram (EEG), electrocardiogram (ECG), and blood pressure. Such transmission is performed via Wireless Medical Sensor Network (WMSN) while diagnosing patients remotely through Internet-of-Medical-Things (IoMT). The sensitive data transmitted through WMSN from IoMT over an insecure channel is vulnerable to several threats and needs proper attention to be secured from adversaries. In contrast to addressing the security of all associated entities involving patient monitoring in the healthcare system or ensuring the integrity, authorization, and nonrepudiation of information over the communication line, no one can guarantee its security without a robust authentication protocol. Therefore, we have proposed a lightweight and robust authentication scheme for the network-enabled healthcare devices (IoMT) that mitigate all the identified weaknesses posed in the recent literature. The proposed protocol's security has been analyzed formally using BAN logic and ProVerif2.02 and informally using pragmatic illustration. Simultaneously, at the end of the paper, the performance analysis result shows a delicate balance of security with performance that is often missing in the current protocols.