Angiotensin-converting enzyme 2 (ACE2) polymorphisms and susceptibility of severe SARS-CoV-2 in a subset of Pakistani population.

Science is digging for the varied presentation of COVID-19 patients exposed to the same risk factors, and medical conditions may be influenced by the presence of polymorphic genetic variants. This study investigated the link between ACE2 gene polymorphisms and the severity of SARS-CoV-2. This cross-sectional study recruited COVID-19 PCR-positive patients by consecutive sampling from Ziauddin Hospital from April to September 2020. DNA was extracted from whole blood, followed by gene amplification and Sanger's sequencing. Most of the patients, 77: 53.8%, were serious. Males were higher (80; 55.9%) with age more than 50 years (106: 74.1%). We found 22 ACE2 SNPs. rs2285666 SNP was most prevalent with 49.2% CC, 45.2% TT, 4.8% CT heterozygosity, and 0.8% AA genotypes. Variants with multiple genotypes were also insignificantly associated with the severity of COVID-19 in the analysis of the dominant model. Only rs2285666 had a significant statistical link with gender (p-value 0.034, OR; 1.438, CI; 1.028-2.011) while rs768883316 with age groups (p-value 0.026, OR; 1.953, CI; 1.085-3.514). Haplotypes ATC of three polymorphisms (rs560997634, rs201159862, and rs751170930) commonly found in 120 (69.77%) and TTTGTAGTTAGTA haplotype consisting of 13 polymorphisms (rs756737634, rs146991645, rs1601703288, rs1927830489, rs1927831624, rs764947941, rs752242172, rs73195521, rs781378335, rs756597390, rs780478736, rs148006212, rs768583671) in 112 (90.32%) had statistically significant association with the severity having p = value 0.029 and 0.001 respectively. Males of old age and diabetics are found to have more severe COVID-19 infection in the current study. We also found that common ACE2 polymorphism rs2285666 influences the susceptibility of acquiring the severe SARS-CoV-2 infection.

Emerging novel sequence types of Staphylococcus aureus in Pakistan.

BACKGROUND: Despite an increasing incidence of Staphylococcus aureus infection and dissemination in Pakistan, the epidemiology of different Staphylococcus aureus research clones has been the subject of only a small number of investigations. By analyzing the collected data sequence, this study was designed to study the epidemiology of Staphylococcus aureus in the area using multilocus sequence typing (MLST). METHODS: A total of 1015 staphylococcus strains collected from the city's tertiary care facilities were biochemically screened, followed by antimicrobial susceptibility testing against a panel of 13 antibiotics. Analyzed methicillin-resistant Staphylococcus aureus (MRSA) was subjected to molecular characterization using multilocus sequence typing (MLST), clonal complex analysis, recombination testing, and phylogenetic analysis. RESULTS: Approximately 421 bacteria were verified as Staphylococcus aureus by biochemical analysis. 57% of the isolates exhibited multidrug resistance, of which 89% were found to be methicillin-resistant Staphylococcus aureus (MRSA). MLST results in a total of 39 sequence types (ST) and 5 clonal complexes (CC), out of which twenty-two STs were newly documented worldwide. The most common CC identified was CC8. The direct sequencing data also revealed significant shifts at MLST loci, with point mutations resulting in the aroE-343 and tpi-278 alleles. CONCLUSIONS: This study concludes that there is high diversity in the locally circulating clones of Staphylococcus aureus present in nature and that they are defined by their geographic epidemiology. These findings have practical implications for public health, including the need for tailored infection control strategies, antibiotic stewardship, global surveillance, and a deeper understanding of bacterial evolution.

A rare case of perforated jejunal diverticula of an uncommon origin.

Jejunal diverticula are often asymptomatic and rare, so they can go unnoticed until serious complications like obstruction, bleeding, perforation, volvulus, or diverticulitis occur. Elderly people over 60 are more likely to have this condition.

Unconventional but effective: breaking through IBS-D clinical practice guidelines - correspondence.

Irritable Bowel Syndrome (IBS) is a chronic, one of the commonest and persistent gastrointestinal (GI) disorder. Previously, the management plan for IBS-D included enhancing awareness; first line treatment included an increased dietary fiber intake, opioids for diarrhea and antispasmodics for pain management. A recent treatment guideline by the American Gastroenterology Association (AGA) suggests a modified approach to treating patients with IBS-D. Eight drug recommendations were made, and a set of instructions on when to employ which medication was devised. With the incorporation of these structured guidelines, a more tailored and focused approach to IBS management may become plausible.

Acute liver failure secondary to the use of unmonitored drugs and herbal supplements: an underreported and serious issue.

Acute liver failure (ALF) is a potentially fatal illness marked by the abrupt development of jaundice, coagulopathy, and hepatic encephalopathy (HE) in persons having no previous history of hepatic disease. It is a relatively uncommon illness, having an incidence of 1 to 8 per million people. Hepatitis A, B, and E viruses have been documented as the most prevalent etiologies of acute liver failure in Pakistan and other developing nations. However, ALF may also occur secondary to toxicity caused by the unmonitored overdosing and toxicity of traditional medicines, herbal supplements, and alcohol. Similarly, in some instances, the etiology remains unknown. Herbal products, alternative, and complementary therapies are frequently practiced across the globe for treating various illnesses. In recent times, their use has gained much popularity. Indications and the use of these supplementary drugs vary significantly. The majority of these products have not gained approval from Food and Drug Administration (FDA). Unfortunately, the incidence of documented adverse effects linked to the usage of herbal products has increased recently, but still, these events are underreported, and the condition is known as drug-induced liver injury (DILI) and herb-induced liver injury (HILI). The estimated total herbal retail sales increased from $4230 million in 2000 to $6032 million in 2013, representing a total of 42 and 3.3% per annum increase. To reduce the occurrence of HILI and DILI, physicians in general practice settings should inquire about patients' understanding of potential toxicity with the consumption of hepatotoxic and herbal medicines.

Dreadful infectious disease outbreaks threaten flood-ravaged pakistan: short communication.

A rise in the incidence of water-borne, communicable illnesses, and viral outbreaks in Pakistan follows periods of heavy rainfall. Due to climate change, floods and droughts have had devastating effects on human health by facilitating the spread of infectious illnesses including cholera, malaria, typhoid, dengue fever, and viral hepatitis A. Food instability, starvation, malnutrition, and a lack of potable water are only some of the indirect effects of flooding on health. Recently, one of the worst floods in history devastated Pakistan, affecting more than 333 million people along with a significant portion of the nation submerged. Malaria, dengue fever, and other ailments are on the rise in Pakistan, threatening to overwhelm the country's healthcare infrastructure. There is an urgent need for preventative measures in Pakistan to cope with dreadful outbreaks.

Inflammatory markers and COVID-19 disease progression.

BACKGROUND: The COVID-19 pandemic has resulted in a global humanitarian crisis. Despite ongoing research, transmission risks and many disease characteristics remained unclear. Most patients have displayed elevated levels of certain inflammatory markers, which we sought to investigate further in relation to disease severity. The aim of this study was to examine the correlation between inflammatory markers and the severity of COVID-19 among patients. METHODS: We conducted a cross-sectional study from April to September 2020, involving 143 COVID-19 PCR-positive patients from Ziauddin Hospital. Electronic patient records provided data on demographics, clinical status, and laboratory results. RESULTS: The majority of PCR-positive patients were elderly males with comorbidities such as diabetes and hypertension. Almost all patients exhibited increased levels of various inflammatory markers, with procalcitonin (97.2%) being the most common. Statistically significant differences were observed in the levels of TLC (p = 0.005), CRP (p = 0.001), LDH (p = 0.001), Ferritin (p = 0.001), D-dimer (p = 0.001), and procalcitonin (p = 0.028), in relation to COVID-19 severity. CONCLUSIONS: The data suggest a significant association between levels of inflammatory markers and COVID-19 severity. All markers, except procalcitonin, demonstrated a significant correlation with disease severity. These results could enhance our understanding of COVID-19 pathogenesis and help predict and manage severe cases.

Upadacitinib for Spondyloarthritis; A new treatment option.

Axial spondyloarthritis, often known as ankylosing spondylitis (AS), is an inflammatory condition that mostly affects the axial skeleton. Axial spondyloarthritis is further subdivided into non-radiographic and radiographic AS. For radiographic axial spondyloarthritis, the male-to-female ratio is two to one, while for non-radiographic axial spondyloarthritis, it is one to one, often manifesting in the third decade of life. Effective treatment for AS includes non-steroidal anti-inflammatory medications (NSAIDs) and TNF blockers. All articular symptoms of AS have been seen to improve significantly when treated with TNF inhibitors such as Etanercept, Adalimumab, Infliximab, Certolizumab, and Golimumab. Upadacitinib, has proven to be significantly efficacious in the management of active non-radiographic axial spondyloarthritis (nr-axSpA), with MRI-based or blood tests displaying objective evidence of inflammation, an increased C-reactive protein, and an unsatisfactory response to Non-steroidal anti-inflammatory drug (NSAIDs). the lack of oral therapy options, and the stigma associated with surgical intervention makes it crucial to offer an unambiguous treatment choice, especially in light of the disease's strong heredity. Thus, Upadacitinib's usage in the treatment of nr-axSpA and its clinical trial is a significant step toward the availability of an internationally-approved medicine for the treatment of nr-axSpA.

Increased burden of booster shots for COVID-19 amidst vaccine hesitancy in Pakistan.

Pakistan is dealing with the fifth wave brought on by the new type, Omicron (or B.1.1.529) with 1,547,795 confirmed cases with 30,452 deaths of COVID-19, as reported by World Health Organization (WHO) from 2020 to 2022. Vaccination is the best tool to curb this pandemic and fight against the new variants as it reduces the likelihood that the disease will be severe. A two-dose regimen of the BNT162b2 vaccine provides 95% protection to people aged 16 years and above, against the novel coronavirus. However, like in other developing countries, the vaccination campaign in Pakistan is hampered due to vaccine hesitation. This might not be the last mutation the world shall face. As with any other virus, the corona-virus is also expected to mutate frequently in the future, making annual booster shots the only way to stay significantly immunized against this deadly virus. Communication and counseling are needed to build their trust while taking care of social inequalities in the population. The authorities must intensify their efforts and should address this very important issue.

A global review of racial, ethnic and socio-economic disparities in multisystem inflammatory syndrome in children related to COVID-19.

With over 500 million confirmed cases and 6.2 million deaths worldwide, the novel coronavirus has highlighted the underlying disparities in healthcare, unpreparedness to deal with a new disease and the need for monitoring and surveillance for a post-infectious syndrome as well as complicated diseases. Initially, children were thought to be spared but reports of a new phenomenon manifesting as Kawasaki-like disease, toxic shock syndrome, and multi-system inflammatory syndrome, which developed after a few weeks of severe COVID-19 infection, emerged in the pediatric population. As the pandemic progressed, increased prevalence of multi-system inflammatory syndrome in children (MIS-C) related to COVID-19 was seen in non-Hispanic blacks, Asians, and Latinos as compared to the white population drawing attention to a possible role of ethnicity and socio-economic disparities. The CDC currently reports that 31% of MIS-C cases were seen in Black Non-Hispanics and 26% in Latinos, who were historically more affected in previous pandemics. Furthermore, MIS-C cases in developing countries showed higher mortality as compared to high-income countries, which points toward the role of social determinants of health and limitations in a low-resource set up in increasing the disease burden of MIS-C, which should be treated as a public health emergency. Our review highlights the role of ethnicity, socio-economic factors, comorbidities, and differences in populations affected by MIS-C in high-income vs. low- and middle-income countries.