Pakistan's HIV high-risk populations: Critical appraisal of failure to curtail spread beyond key populations.

Pakistan has been a hub of several HIV outbreaks over the last 2 decades, with four major outbreaks being registered since 2018. There has been a recent rise in HIV infections, especially in high-risk populations, mainly consisting of people who inject drugs, men who have sex with men, prisoners, the transgender women community, and female sex workers. Consistently poor infection control practices, unregulated unsafe blood transfusion, questionable ethical practices by healthcare providers, and a general lack of awareness are the main drivers of recent HIV outbreaks, with these issues exacerbated by the presence of untrained health care providers. To stop the spread of HIV systemically and sustainably, aggressive measures need to be taken at all levels by all concerned stakeholders that not only deal with building up testing, tracing, and treatment capabilities but also address underlying grassroots problems that have largely been ignored to date.

Pathways to prevention: insights on stemming HIV outbreaks in Larkana, Pakistan.

In the past two decades, Pakistan has faced multiple human immunodeficiency virus outbreaks, with Larkana appearing to be the hub of such outbreaks. While the previous Larkana outbreaks happened in high-risk populations, the alarming outbreak in 2019 occurred in a low-risk paediatric population, raising several concerning questions. Human immunodeficiency virus infections spilling into the general population is indicative of a steady increase in the number of cases, and the failure of control strategies to stem the concentrated epidemic from evolving. Although several causative factors have been identified from previous outbreaks, the one that occurred in 2019 may have been influenced by an additional, hitherto unexplored factor; child sexual abuse. The current narrative review was planned to summarise human immunodeficiency virus risk factors and causes identified in previous Larkana epidemics, to explore potential reasons for the outbreaks in children, and to discuss possible steps needed for stemming human immunodeficiency virus outbreaks in Pakistan.

Efficacy and safety of bedaquiline and delamanid in the treatment of drug-resistant tuberculosis in adults: A systematic review and meta-analysis.

Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st, 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.

Review of sepsis in Pakistan: how far have we come?

Pakistan is a low-middle-income country (LMIC) with a high burden of sepsis, yet there is a profound dearth of data regarding sepsis with no comprehensive review. In Pakistan, access to competent healthcare services is delayed and in places, often not available. Patients may present with sepsis after common community-acquired infections; the commonest sources of sepsis are the respiratory tract followed by the urinary tract. Gram-negative organisms are responsible for a large majority of cases of sepsis. Unfortunately, compliance with sepsis guidelines remains poor, and sepsis-related statistics do not seem to be improving significantly. Adult sepsis presents a significant burden on healthcare services, particularly in LMICs, and is a leading cause of morbidity and mortality. Many factors which affect outcomes and cost of care are amenable to prompt interventions. Consequently, there is a dire need to make concentrated efforts in implementing simple, cost-effective, and context-specific guidelines and monitoring strategies regarding the diagnosis and management of sepsis. The collection and analysis of information on sepsis in Pakistan hence remains imperative, in order to prospectively assess the effects of guideline compliance on outcomes and to formulate and refine new schemata to address emerging problems.

Feasibility, enablers and challenges of using timeliness metrics for household contact tracing and TB preventive therapy in Pakistan.

INTRODUCTION: Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan. METHODS: We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions). RESULTS: From January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment ("first 7"). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing ("next 1"). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening ("second 7"). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the "second 7" component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines. CONCLUSIONS: Field staff found "7-1-7" timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients.

Etiology of Acute Infectious Meningitis and Meningoencephalitis in Karachi, Pakistan: Retrospective Observational Study from a Tertiary Care Center.

Meningoencephalitis (ME) is potentially fatal and is caused by a wide array of pathogens. Diagnostic and health-care access gaps prevent accurate estimation of the pathogen-specific burden in low-resource settings. We present pathogen-specific etiologies among patients hospitalized with ME in Karachi, Pakistan. We performed a retrospective hospital database evaluation of pathogen etiology and outcomes of community-acquired infectious ME at a single tertiary care center in Karachi, Pakistan. Annual rates of hospitalization (ARH) were calculated by adjusting for missed cases and are reported per 100,000 population. From May 2017 to April 2020, 522 episodes of infectious ME were identified in 514 patients. The overall ARH from ME was 5.7/100,000 population (95% CI, 5.1-6.1). Among children younger than 5 years, the ARH was 9.8/100,000 population (95% CI, 8.1-11.8). Unknown causes of ME resulted in the greatest burden, with an ARH of 1.9/100,000 population (95% CI, 1.7-2.2). Among known causes, the greatest burden of hospitalizations resulted from tuberculous ME (0.8/100,000; 95% CI, 0.6-0.97), followed by pneumococcal and enteroviral ME (both 0.6/100,000 population; 95% CI, 0.5-0.8). The burden of ME caused by pathogens preventable through vaccination or public health measures outweighed that of ME from other causes (P = 0.0092, Fisher's exact test). We report a broad range of pathogens causing ME in southern Pakistan and show a high burden of preventable illness. Synergistic actions to improve diagnostic strategies, increase vaccinations, and introduce measures to reduce water-borne and vector-borne diseases are required to reduce the ME burden in Pakistan and prevent future outbreaks.

Interleukin-6 (IL-6) as a Predictor of Clinical Outcomes in Patients with COVID-19.

BACKGROUND: Interleukin-6 (IL-6) has been known to be involved in immune regulation, inflammatory response, and metabolism. It is also recognized as the major cause to underscore the pathology of severe COVID-19 patients. However, it remains to be seen if IL-6 is superior to other inflammatory biomarkers in ascertaining clinical severity and mortality rate for COVID-19. This study aimed to determine the value of IL-6 as a predictor of severity and mortality in COVID-19 patients and compare it with other pro-inflammatory biomarkers in the South Asian region. METHODS: An observational study was conducted, including all adult SARS-CoV-2 patients who had undergone IL-6 testing from December 2020 to June 2021. The patients' medical records were reviewed to collect demographic, clinical, and biochemical data. Other pro-inflammatory biomarkers apart from IL-6 included Neutrophils to Lymphocyte Ratio (NLR), D-dimer, C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and procal-citonin for analysis. SPSS version 22.0 was utilized. RESULTS: Out of the 393 patients who underwent IL-6 testing, 203 were included in the final analysis with a mean (SD) age of 61.9 years (12.9) and 70.9% (n = 144) were male. Fifty-six percent (n = 115) subjects had critical disease. IL-6 levels were elevated (> 7 pg/mL) in 160 (78.8%) patients. Levels of IL-6 significantly correlated with age, NLR, D-dimer, CRP, ferritin, LDH, length of stay, clinical severity, and mortality. All the inflammatory markers were significantly increased in critically ill and expired patients (p < 0.05). The receiver operator curve showed that IL-6 had the best area under the curve (0.898) compared to other pro-inflammatory biomarkers for mortality with comparable results for clinical severity. CONCLUSIONS: Study findings show that though IL-6 is an effective marker of inflammation and can be helpful for clinicians in recognizing patients with severe COVID-19. However, we still need further studies with larger sample size.

Diagnostic value of bronchoscopy in Sars-Cov-2 infection: A systematic review.

OBJECTIVE: To investigate the diagnostic performance of bronchoscopy in patients with coronavirus disease 2019 infection. METHODS: The systematic review was conducted in April 2021 and comprised search of published articles and preprint servers for original articles assessing diagnostic performance of bronchoscopy in patients with suspected coronavirus disease 2019 infection. The primary outcome of interest was diagnostic sensitivity of bronchoalveolar lavage in the patients. The quality of each study was assessed using the Quality Assessment, Data Abstraction and Synthesis-2 tool. RESULTS: Of the 29 full-text articles assessed for eligibility, 4(13.8%) were included collectively comprising 209 patients who had undergone bronchoalveolar lavage. Mean sensitivity of bronchoalveolar lavage was 83.5% ± 10.63 (range: 68.2-940%). Overall, the 4 studies had an unclear or low risk of bias. CONCLUSIONS: Limited data suggested that bronchoscopy with bronchoalveolar lavage did not have reliably higher diagnostic sensitivity than that reported for either nasopharyngeal or oropharyngeal swabs.

Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

High-Dose Rifampicin Regimen for Pulmonary TuberculosisThis randomized, controlled trial tested the efficacy and safety of high-dose rifampicin (1200 or 1800 mg/d) as part of the treatment regimen for pulmonary tuberculosis. Four-month high-dose rifampicin regimens had no dose-limiting side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen.

Tuberculosis and diabetes mellitus: Relating immune impact of co-morbidity with challenges in disease management in high burden countries.

Mycobacterium tuberculosis (MTB) is the causative agent of TB. TB incidence is high in many low resource settings where limited health systems make it difficult for screening of co-morbid conditions. Susceptibility to TB is increased with coincident diabetes mellitus (DM) or prediabetes. DM leads to chronic, subclinical inflammation in the host leading to compromised protective immunity against MTB, impacting TB treatment. This review focuses on the immunological impact of DM and prediabetes on TB infections, highlighting the importance of having effective diagnostic, treatment and management programs for early identification of hyperglycemia in TB patients to improve treatment outcomes. Further, it describes challenges in monitoring of TB and DM co-morbidity in a high-burden setting.

Phylodynamic signatures in the emergence of community-associated MRSA.

Community-associated, methicillin-resistant Staphylococcus aureus (MRSA) lineages have emerged in many geographically distinct regions around the world during the past 30 y. Here, we apply consistent phylodynamic methods across multiple community-associated MRSA lineages to describe and contrast their patterns of emergence and dissemination. We generated whole-genome sequencing data for the Australian sequence type (ST) ST93-MRSA-IV from remote communities in Far North Queensland and Papua New Guinea, and the Bengal Bay ST772-MRSA-V clone from metropolitan communities in Pakistan. Increases in the effective reproduction number (Re) and sustained transmission (Re > 1) coincided with spread of progenitor methicillin-susceptible S. aureus (MSSA) in remote northern Australian populations, dissemination of the ST93-MRSA-IV genotype into population centers on the Australian East Coast, and subsequent importation into the highlands of Papua New Guinea and Far North Queensland. Applying the same phylodynamic methods to existing lineage datasets, we identified common signatures of epidemic growth in the emergence and epidemiological trajectory of community-associated S. aureus lineages from America, Asia, Australasia, and Europe. Surges in Re were observed at the divergence of antibiotic-resistant strains, coinciding with their establishment in regional population centers. Epidemic growth was also observed among drug-resistant MSSA clades in Africa and northern Australia. Our data suggest that the emergence of community-associated MRSA in the late 20th century was driven by a combination of antibiotic-resistant genotypes and host epidemiology, leading to abrupt changes in lineage-wide transmission dynamics and sustained transmission in regional population centers.

Association of Chest Xray (CXR) findings with outcomes in COVID-19 Patients.

Objective: To investigate chest radiography findings in suspected coronavirus disease-2019 patients in a tertiary care setting. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of coronavirus disease-2019 cases admitted to the tertiary care centre from March 1 to March 30, 2020. A predesigned proforma was used to gather data, including demographics, like age and gender, co-morbidities, presenting symptoms and chest radiography findings during the admission. Length of stay and mortality were the outcome measures. Data was analysed using SPSS 22. RESULTS: Of the 154 suspected cases, 46(29.8%) tested positive for coronavirus disease-2019; 29(63%) males and 17(37%) females with a mean age of 50.7±19.1 years. Abnormal chest radiography was noted in 25(54.3%) cases, with bilateral pulmonary infiltrates being the most common finding 19(41.3%). Mortality was the outcome in 7(28%) of these cases, and the mean length of hospital stay was 9.3±7.3 days. Abnormal chest radiography findings were associated with an increased risk of mortality (p=0.009) and a longer hospital stay (p=0.017). Conclusion: Abnormal chest radiography findings were frequently seen in coronavirus disease-2019 patients and were also associated with increased risk of mortality and prolonged hospital stay.

Country data on AMR in Pakistan in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review the current situation with respect to AMR in Pakistan and initiatives addressing it. Identifying areas where more information is required will provide a call to action to minimize any further rises in AMR and improve patient outcomes. METHODS: National AMR initiatives, antibiotic use and prescribing in Pakistan, and availability of susceptibility data, in particular for the key community-acquired respiratory tract infection (CA-RTI) pathogens (Streptococcus pneumoniae and Haemophilus influenzae) were identified. National and international antibiotic prescribing guidelines for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) commonly used locally were also reviewed, plus local antibiotic availability. Insights from a local clinician and clinical microbiologist were sought to contextualize this information. CONCLUSIONS: Pakistan is active in developing initiatives to address AMR such as compiling a National Action Plan. However, antibiotic consumption is high and although there is legislation in place prohibiting over-the-counter purchase of antibiotics, this is still possible. Healthcare professionals use local and international antibiotic prescribing guidelines for CA-RTIs when managing patients. As highlighted by the clinical microbiologist's expert comments, surveillance of AMR in locally prevalent microorganisms is lacking. A more standardized inclusive approach in developing local guidelines, using up-to-date local surveillance data of isolates from community-acquired infections, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical outcomes for patients.

Risk factors for intensive care unit admission and mortality among adult meningitis patients.

OBJECTIVE: To assess the risk factors for intensive care unit admission and inpatient all-cause mortality among adult meningitis patients. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised of patients of either gender aged ≥18 years diagnosed with bacterial, viral, or tuberculous meningitis between July 2010 and June 2019. Multivariable logistic regression analyses were used to explore independent predictors of inpatient mortality and intensive care unit admission. Data was analysed using SPSS 24. RESULTS: Of the 929 patients with suspected meningitis, 506(54.5%) had confirmatory diagnosis. Of them, 303(59.9%) were males. The overall median age of the sample was 47.0 years (interquartile range: 33.0 years). The most common aetiology was bacterial meningitis 324(64%), followed by viral meningitis 141(27.9%). Incidence of inpatient mortality was 53(10.5%), while 75(14.8%) patients required intensive care unit admission. Tuberculous aetiology, intensive care unit admission, concurrent encephalitis, hydrocephalus, inpatient neurosurgery, and longer length of hospital stay were predictors of mortality (p<0.05). Non-indication of blood culture was found to be associated with reduced risk of mortality (p<0.05). For intensive care unit admission, diabetes mellitus, presentation with seizure, imaging suggestive of meningitis, and inpatient neurosurgery were associated with higher risk of admission, while hypertension, presentation with headache, viral aetiology and non-indication of blood culture reduced the risk (p<0.05). CONCLUSIONS: Adult meningitis patients tend to have poor expected outcomes, and their management strategies should be planned accordingly.

Synthesis, characterization, and evaluation of the antifungal properties of tissue conditioner incorporated with essential oils-loaded chitosan nanoparticles.

PURPOSE: This study aims to investigate new tissue conditioner (TC) formulations involving chitosan nanoparticles (CSNPs) and essential oils (EO) for their antifungal potential, release kinetics, and hardness. MATERIALS AND METHODS: CSNPs were synthesized, and the separate solutions of CSNP were prepared with two types of EO, i.e., Oregano oil and Lemongrass. The EO was loaded separately in two concentrations (200 µL and 250 µL). The blank and EO-loaded CSNPs were screened against Candida albicans (C. albicans), and their minimum inhibitory concentration was established. GC Reline™ (GC corporation, USA) TC was considered a control group, whereby the four experimental groups were prepared by mixing CSNPs/EO solutions with TC powder. The antifungal effectiveness (C. albicans) and release kinetics behavior (1-6 h, 24 h, 48 h, and 72 h) was investigated. The Shore A hardness of control and experimental groups was evaluated in dry and wet modes (deionized water and artificial saliva). For statistical analysis, SPSS version 22 was used to do a one-way ANOVA post-hoc Tukey's test. RESULTS: Compared to the control group, TCs containing blank CSNPs and CSNPs loaded with EO showed 3 and 5 log reductions in C. albicans growth, respectively. A significantly high antifungal effect was observed with TC containing lemongrass essential oil (200 µL). The continuous release of EO was detected for the first 6 hours, whereas completely stopped after 48 hours. Mean hardness values were highest for dry samples and lowest for samples stored in artificial saliva. The statistically significant difference within and between the study groups was observed in mean and cumulative essential oils release and hardness values of TCs over observed time intervals irrespective of storage media. CONCLUSION: TCs containing essential-oil-loaded CSNPs seem a promising alternative treatment of denture-induced stomatitis, however, a further biological analysis should be taken.

Predicting Development Of Critical Illness In Patients With Covid-19 Presenting To A Tertiary Care Hospital In A Developing Country.

BACKGROUND: With the increasing number of COVID-19 patients and limited resources available to accommodate them, there is a need for risk stratification tools to ensure better utilization of resources. METHODS: We conducted a retrospective observational cohort study in patients discharged from the COVID designated areas of a large tertiary care hospital in Karachi, Pakistan from the 1st of May to the 31st of July, 2020. 581 patients were included and the COVID GRAM score was calculated at the time of admission and patients developing critical disease as per COVID GRAM study criteria (need of intensive care unit admission, invasive ventilation or death) after 24 hours of admission were noted. RESULTS: The mean age of the study population was 56.3±14.8 years. Patients that developed critical illness (as per COVID GRAM study criteria) beyond 24 hours after admission had higher COVID GRAM scores at admission versus those that did not (183.2±80.7 versus 130.3±42.6). The Area under the Receiver Operator Curve for the COVID gram score to predict critical illness in the study population was 0.802 (95% confidence interval, 0.753-0.850). On binary logistic multivariable regression analysis, the COVID GRAM and SOFA scores on admission and need of ICU admission during hospitalization were significant predictors of mortality 24 hours after admission. CONCLUSIONS: The COVID GRAM score is a useful risk assessment tool and can be used for appropriate allocation and prioritization of resources where they are most needed.

Nasopharyngeal Tuberculosis.

Tuberculosis is a well-known communicable infectious disease and can involve almost any organ of the body. Upper respiratory tract involvement is seen in only 1.9% and involvement of the nasopharynx is even rarer, accounting for only 0.1%. The occurrence of nasopharyngeal tuberculosis (NPTB) is very rare even in endemic areas. Herein, we report two cases of NPTB in which patients had the previous history of chronic ear infection; and later were found to have NPTB. Initial symptoms of NPTB can be vague and easily be misdiagnosed. The literature is scarce on NPTB. To the best of our knowledge, no such cases have ever been reported from Pakistan. Although the incidence of NPTB is very low since we live in a country where tuberculosis incidence is really high, its possibility should be kept in mind as one of the differential diagnoses. Key Words: Nasopharyngeal, Tuberculosis, Otitis media, Fungal, Infection.

Etiology, clinical characteristics, and outcome of infective endocarditis: 10-year experience from a tertiary care center in Pakistan.

This study was conducted to assess the clinical characteristics, causative agents, complications, and outcomes of infective endocarditis (IE) among patients presenting to our tertiary care center over the last decade. This retrospective cohort study included all adult patients admitted to the Aga Khan University Hospital with the diagnosis of IE over a ten-year period from 2010 to 2020.  Outcomes variables included complications during hospitalization, surgical intervention, mortality, and length of stay. We identified a total of 305 cases out of which 176 (58%) were males and 129 (42%) were females. The mean age of the patients was 46.9±18.8 years. 95 (31%) had prosthetic valves in place. Staphylococcus aureus was isolated in 54 (39%) patients followed by coagulase-negative Staphylococcus in 23 (17%). Echocardiography revealed vegetations and abscesses in 236 (77%) and 4 (1%) patients, respectively. The most common valvular complication was mitral valve regurgitation found in 26 (9%) patients, followed by tricuspid valve regurgitation in 13 (4%) patients and aortic valve regurgitation in 11 (3%) patients. Furthermore, 81 (27%) patients suffered from heart failure and 66 (22%) from a stroke during hospitalization. The mean hospital length of stay was 10.4 ± 10.6 days. 64 (21%) patients required surgical repair and the overall mortality rate was 25%. Prosthetic valve endocarditis (OR = 3.74, 95% CI = 2.15-6.50, p<0.001), chronic kidney disease (OR = 2.51, 95% CI = 1.15-5.47, p=0.036), previous stroke (OR = 2.42, 95% CI = 1.18-4.96, p=0.026), and ischemic heart disease (OR = 3.04, 95% CI = 1.50-6.16, p=0.003) were significantly associated with an increased risk of mortality. In conclusion, our study provided valuable data on the clinical characteristics and outcomes of patients with IE in a developing country. S. aureus was the most common causative agent. Heart failure and stroke were the most common complications. The presence of prosthetic valves, history of chronic kidney disease, ischemic heart disease and previous stroke were associated with a significantly increased risk of mortality. Surgical management was not associated with improved outcomes.

Latent M. tuberculosis infection is associated with increased inflammatory cytokine and decreased suppressor of cytokine signalling (SOCS)-3 in the diabetic host.

Tuberculosis (TB) outcomes are worsened by type II diabetes mellitus (DM). Protective immunity against Mycobacterium tuberculosis (MTB) is driven by cytokines. Latent TB (LTBi) is common but its effect on the diabetic host is not well understood. We investigated mycobacterial antigen-stimulated responses in peripheral blood mononuclear cell (PBMC) isolated from healthy endemic controls (EC), those with LTBi, DM groups with and without LTBi, as compared with TB patients. Cytokines were measured using a Luminex-based assay. Gene expression was determined by RT-PCR. In DM-LTBi cases, PPD-stimulated proinflammatory cytokines; IFN-γ, IL-6, IL-2, TNF-α and GM-CSF and anti-inflammatory cytokines, IL-5 and IL-13 were raised as compared with EC. DM-LTBi PPD-stimulated IFN-γ, IL-6 and TNF-α mRNA titres were found raised in DM-LTBi, whilst suppressor of cytokine signalling (SOCS)-3 expression was lowered. Within DM cases, stratification based on HbA1c levels revealed raised IFN-γ but lowered IL-6 gene expression in those with controlled levels as compared with uncontrolled glycaemic levels. Further, SOCS1 expression levels were found higher in DM cases with controlled glycaemia when compared with EC. Overall, we show that diabetics with LTBi manifest raised levels of inflammatory and anti-inflammatory cytokines concomitant with reduced SOCS3 mRNA expression. Reduced glycaemic control results in further inflammatory dysregulation impacting conversing impacting IFN-γ and IL-6 activation. These results suggest that dysregulated immune activation in diabetes is exacerbated by LTBi, lack of glycaemic control may further compromise immunity against MTB infection.

Outcome of Atrial Fibrillation in Patients With Sepsis.

Background Atrial fibrillation (AF) is one of the most frequent arrhythmias in critically ill patients. Sepsis is a major cause of inpatient mortality and it has been associated with cardiac arrhythmias. The objective of this study was to study the outcome of atrial fibrillation in patients who are admitted with sepsis. Methods This is a prospective, single-center cohort study of patients admitted to the Medicine Department between June 1, 2019, and November 30, 2019. The inclusion criteria were adult patients with sepsis and septic shock. In this study, 113 patients were enrolled and outcomes were compared between the group that developed atrial fibrillation during the hospital stay and the group without atrial fibrillation. Results There were 57 (50.4%) patients with AF including 23 (20.4%) who also had a prior history. Total inpatient mortality was 42 (37.2%), of which 17 patients (40.5%) had AF. AF was not found to be associated with higher mortality or increased length of hospital stay (p-value 0.103 and 0.858, respectively). Conclusion AF was not found to be a cause of higher mortality in patients with sepsis or septic shock. There is a need for larger-scale studies to find out the causes of high inpatient mortality in sepsis and the need for local guidelines regarding the management of AF in critically ill patients.