Chronic obstructive pulmonary disease and emerging ER stress-related therapeutic targets.

COPD pathogenesis is frequently associated with endoplasmic reticulum stress (ER stress) progression. Targeting the major unfolded protein response (UPR) branches in the ER stress pathway may provide pharmacotherapeutic selection strategies for treating COPD and enable relief from its symptoms. In this study, we aimed to systematically review the potential role of the ER stress inhibitors of major UPR branches (IRE1, PERK, and ATF6) in COPD-related studies and determine the current stage of knowledge in this field. The systematic review was carried out adhering to the PRISMA checklist based on published studies obtained from specific keyword searches of three databases, namely PubMed, ScienceDirect and Springer Database. The search was limited to the year 2000-2022 which includes all in vitro studies, in vivo studies and clinical trials related to the application of ER stress inhibitors toward COPD-induced models and disease. The risk of bias was evaluated using the QUIN, SYRCLE, revised Cochrane risk of bias tool for randomized trials (RoB 2.0) and NIH tool respectively. A total of 7828 articles were screened from three databases and a final total of 37 studies were included in the review. The ER stress and UPR pathways are potentially useful to prevent COPD progression and attenuate the exacerbation of COPD and related symptoms. Interestingly, the off-target effects from inhibition of the UPR pathway may be desirable or undesirable depending on context and therapeutic applications. Targeting the UPR pathway could have complex consequences as the production of ER molecules involved in folding may be impaired which could continuously provoke misfolding of proteins. Although several emerging compounds were noted to be potentially useful for targeted therapy against COPD, clinical studies have yet to be thoroughly explored.

Comparison of analgesic effects of Gabapentin and Paracetamol post-operatively in patients with hand injury.

OBJECTIVES: To compare the analgesic effects of gabapentin and paracetamol post-operatively in patients with hand injury. METHODS: The double-blind, randomised control trial was conducted at the Department of Plastic Surgery, Dow University of Health Sciences, Karachi, from March to August 2019, and comprised subjects aged 18-60 years with hand injury who were randomly divided into group I which received gabapentin 600mg and group II which received paracetamol 1000 mg through anonymous packaging. Pain intensity was assessed using the visual analogue scale along with a self-designed questionnaire which was filled twice post-operatively; first at the time of drug intake once orally allowed; and thereafter six hours later. Data was analysed using SPSS 22. RESULTS: Of the 50 subjects, there were 25(50%) in each of the two groups. Overall, there were 41(82%) males and 9(18%) females. The mean age of the total sample was 28.64±6.72 years. The most frequent side-effect reported in both groups was nausea; 11(44%) in group I and 9(36%) in group II. The least reported side-effect in group I was double vision 1(4%) which was not reported at all in group II and the least reported side-effect was dry mouth 1(4%). The analgesic effect between the groups were not significantly different (p>0.05). CONCLUSIONS: Both gabapentin and paracetamol were found to be effective in pain management, but the latter had slightly better pain control with relatively less side-effects. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04068506.

Results of vertical figure-of-eight tension band suture for fingernail disruption with fractures of distal phalanx.

OBJECTIVE: To give painless and stable fingertips to patients by means of vertical figure-of-eight tension sutures. METHODS: The longitudinal study was carried out from May to October 2019 at the Dow University of Health Science, Civil Hospital, Karachi, and comprised individuals of either gender aged 10-60 years. All patients were surgically managed and were assessed clinically and with radiological films for finger stability and fracture healing during 3-month follow-up. Data was collected using a proforma and was analysed using SPSS 21. RESULTS: Of the 74 patients, 58(78.4%) were males and 16(21.6%) were females. The overall mean age was 28.9±13.23 years. Of the total, 65(88%) were operated under local anaesthesia, while 9(12%) were given general anaesthesia. All 74(100%) patients on early visits had pain and discomfort, 5(6.8%) had infection and none had ischaemic insult. CONCLUSIONS: Using vertical figure-of-eight tension sutures was found to be a simple technique which helped in proper healing of distal phalanx fractures and a non-deformed fingertip.

Surgical Management of Post Burn Hand Deformities.

OBJECTIVE: To evaluate the efficacy of different surgical procedures on post burn contracture of hand. METHODS: A quasi-experimental study design was conducted at the Department of Plastics and Reconstructive Surgery, Dow University of Health Science, DR. Ruth KM Pfau, Civil Hospital, Karachi, Pakistan from 1st June 2019 to 30th November 2019. Ninety-three participants of burned hand contracture of either gender, aged between 6- 60 years were included in the study. Resurfacing surgery with skin graft and loco-regional flaps were done according to type of contracture with individualization for each patient. All patients were kept under follow up for ninety days to assess efficacy of contracture release for each surgical procedure was noted. SPSS version 23 was used to analyse data. RESULTS: Full thickness skin graft (FTSG) was performed in 60.2% cases, 17.2% with split thickness skin graft (STSG) and 12.9% with cross finger flaps. About 25% of recurrence was observed in cross finger flaps, whereas no recurrence was seen in Z-plasties and posterior interosseous flap. The significant association was between recurrence and surgical procedures (p<0.05). CONCLUSION: Z-plasty followed by FTSG was effective in the management of post burn contractures of hand.

It is time to change the way we manage mild asthma: an update in GINA 2019.

Asthma is a heterogeneous lung disease, usually characterised by chronic airway inflammation. Although evidence-based treatments are available in most countries, asthma control remains suboptimal, and asthma-related deaths continue to be an ongoing concern. Generally, it is believed that between 50 to 75% of patients with asthma can be considered as having mild asthma.Previous versions of Global Initiative for Asthma (GINA) suggested that mild asthma in adults can be well managed with either reliever medications, for example, short-acting beta2 agonists (SABA) alone or with the additional use of controllers such as regular low-dose inhaled corticosteroids (ICS). Given the low frequency or non-bothersome nature of symptoms in mild asthma, patients' adherence towards their controller medications, especially to ICS is usually not satisfactory. Such patients often rely on SABA alone to relieve symptoms, which may contribute to SABA over-reliance. Overuse of relievers such as SABAs has been associated with poor asthma outcomes, such as exacerbations and even deaths. The new GINA 2019 asthma treatment recommendations represent significant shifts in asthma management at Steps 1 and 2 of the 5 treatment steps. The report acknowledges an emerging body of evidence suggesting the non-safety of SABAs overuse in the absence of concomitant controller medications, therefore does not support SABA-only therapy in mild asthma and has included new off-label recommendations such as symptom-driven (as-needed) low dose ICS-formoterol and "low dose ICS taken whenever SABA is taken".The GINA 2019 report highlights significant updates in mild asthma management and these recommendations represent a clear deviation from decades of clinical practice mandating the use of symptom-driven SABA treatment alone in those with mild asthma. While the new inclusions of strategies such as symptom-driven (as-needed) ICS-formoterol and "ICS taken whenever SABA is taken" are based on several key trials, data in this context are still only emergent data, with clear superiority of as needed ICS-formoterol combinations over maintenance ICS regimens yet to be established for valid endpoints. Nevertheless, current and emerging data position the clinical asthma realm at a watershed moment with imminent changes for the way we manage mild asthma likely in going forward.

Evaluation of Adverse Reactions Induced by Anti-Tuberculosis Drugs in Hospital Pulau Pinang.

BACKGROUND: The use of multi-drug regimens in tuberculosis (TB) treatment has been associated with undesirable adverse drug reactions (ADRs). This study aims to assess the incidence and impact of ADRs on TB treatment in Hospital Pulau Pinang. METHODS: This cross-sectional study was conducted via retrospective review of outpatients' medical records. Details regarding ADRs were identified by a pharmacist and verified by a consultant respiratory physician. RESULTS: A total of 91 cases, out of 210 patients enrolled in this study, were detected with 75 patients (35.7%) experienced at least one ADR. The three most common ADRs detected were cutaneous adverse drug reactions (CADRs) (21.0%), drug-induced hepatitis (DIH) (7.1%) and gastrointestinal disturbance (4.8%). Pyrazinamide was the most common causative agent and 15.7% of all TB patients required treatment modification due to ADRs. Females were shown to have a higher tendency to develop ADRs than the males in this study (P = 0.009). The development of ADRs was shown not to affect the TB treatment outcomes (P = 0.955). CONCLUSION: The incidence of ADRs in this study was high so it is important to identify the risk factors for ADRs and the individuals who have those risk factors when initiating anti-TB drugs. These individuals require special attention when anti-TB drugs are initiated.

Assessing Airflow Limitation among Smokers in a Primary Care Setting.

BACKGROUND: Many smokers have undiagnosed chronic obstructive pulmonary disease (COPD), and yet screening for COPD is not recommended. Smokers who know that they have airflow limitation are more likely to quit smoking. This study aims to identify the prevalence and predictors of airflow limitation among smokers in primary care. METHODS: Current smokers ≥ 40 years old who were asymptomatic clinic attendees in a primary care setting were recruited consecutively for two months. We used a two-step strategy. Step 1: participants filled in a questionnaire. Step 2: Assessment of airflow limitation using a pocket spirometer. Multiple logistic regression was utilised to determine the best risk predictors for airflow limitation. RESULTS: Three hundred participants were recruited. Mean age was 58.35 (SD 10.30) years old and mean smoking history was 34.56 pack-years (SD 25.23). One in two smokers were found to have airflow limitation; the predictors were Indian ethnicity, prolonged smoking pack-year history and Lung Function Questionnaire score ≤ 18. Readiness to quit smoking and the awareness of COPD were low. CONCLUSIONS: The high prevalence of airflow limitation and low readiness to quit smoking imply urgency with helping smokers to quit smoking. Identifying airflow limitation as an additional motivator for smoking cessation intervention may be considered. A two-step case-finding method is potentially feasible.

Association between Body Mass Index and Hospital Outcomes for COVID-19 Patients: A Nationwide Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused significant morbidity and mortality worldwide. There is limited information describing the hospital outcomes of COVID-19 patients in regard to specific body mass index (BMI) categories. METHODS: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult patients (≥18 years of age) with a primary hospitalization for COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization, and compare the outcomes among patients categorized according to BMI. RESULTS: A total of 305,284 patients were included in this study. Of them, 248,490 had underlying obesity, defined as BMI ≥ 30. The oldest patients were observed to have BMI < 19, while youngest patients were in the BMI > 50 category. BMI < 19 category had the highest crude in-hospital mortality rate. However, after adjusted regression, patients with BMI > 50 (adjusted odds ratio (aOR) 1.63, 95% CI 1.48-1.79, p-value < 0.001) had the highest increased odds, at 63%, of in-hospital mortality compared to all other patients in the study. Patients with BMI > 50 also had the highest increased odds of needing invasive mechanical ventilation (IMV) and mortality associated with IMV compared to all other patient, by 37% and 61%, respectively. Obese patients were noted to have shorter average hospital length of stay (LOS), by 1.07 days, compared to non-obese patients, but there was no significant difference in average hospitalization charges. CONCLUSION: Among obese patients primarily hospitalized with COVID-19, those with BMI ≥ 40 had significantly increased rates of all-cause in-hospital mortality, need for IMV, mortality associated with IMV, and septic shock. Overall, obese patients had shorter average hospital LOS, however, did not have significantly higher hospitalization charges.

Association between COVID-19 preventive behavioral changes and anxiety in Karachi, Pakistan: A cross-sectional pilot study.

Background: COVID-19 has turned into emergent psychological impacts across cohorts with devastating consequences related to preventive measures. Health organizations recommended some preventive measures (e.g., wearing masks, frequent handwashing, etc.) to overcome the COVID-19 pandemic. However, performing these behaviors may increase anxiety among populations. Thus, the present study aimed to investigate the role of behavioral changes to prevent COVID-19 infection and anxiety during the COVID-19 pandemic in Pakistan. Subjects and methods: The present cross-sectional study was conducted for 10 days during July 2020 among the general public of Karachi after the imposition of lockdown amid the COVID-19 pandemic, with a sample size of 331 participants. The questionnaire consisted of three parts i.e., (i) socio-demographics, (ii) perception and preventive behaviors towards COVID-19, and (iii) anxiety-related questions using the Urdu Generalized Anxiety Disorder (GAD-7). The data was analyzed using logistic regression to investigate the association between behavior change and anxiety. Results: Almost half of the participants (i.e., 48.9%) reported being anxious. Although most of the participants were compliant with preventive behavioral changes in their daily lives but no associations between preventive behaviors and anxiety were found. There were significant associations between anxiety and some of the socio-demographic variables (i.e., gender: females were more anxious; age group and marital status single participants were more anxious). Conclusion: Based on the present findings, it is clearly evident that Pakistani people are suffering psychiatric problems during the COVID-19 pandemic. Hence, appropriate initiatives should be adopted as soon as possible. Besides, COVID-19 related preventive behavioral measures are highly recommended to practice without putting anything back for psychological fears.

Eimeria tenella 14-kDa phosphohistidine phosphatase stimulates maturation of chicken dendritic cells and mediates DC-induced T cell priming in a Th1 cytokine interface.

Given the central role of dendritic cells (DCs) in directing cell-mediated immunity, this study investigated the capability of Eimeria tenella 14-kDa phosphohistidine phosphatase (EtPHP14) to mature chicken DCs and initiate DC-induced T cell immunity. With the aim of identifying novel protective Eimeria antigen, EtPHP14 gene was successfully cloned and EtPHP14 recombinant protein (rEtPHP14) was expressed in Escherichia coli expression system. rEtPHP14 binding was identified on the surface of chicken DCs by Immunofluorescence assay. DC phenotypes were evaluated by flow cytometry and results indicated that MHCII, CD80, CD86, CD1.1 and CD11c were up-modulated in DCs following rEtPHP14 treatment. RT-qPCR showed increased transcript levels of DC maturation markers CCL5, CCR7 and CD83 in rEtPHP14-treated DCs. Moreover, transcript profile of genes associated with intracellular signaling pathways that characterize the immunogenic (TLR signaling) or tolerogenic (Wnt signaling) state of DCs revealed that TLR signaling was stimulated and Wnt signaling was inhibited in rEtPHP14-treated DCs. Furthermore, proliferation of T cells and differentiation of CD4+ cells were promoted when rEtPHP14-treated DCs were co-cultured with autologous T cells. DCs incubated with rEtPHP14 alone expressed increased IL-12 and IFN-γ levels while IL-10 and TGF-ß levels remained unaffected. Likewise, similar trend of IFN-γ expression was noted in rEtPHP14 treated DC-T cell coculture, whereas IL-4 expression remained unchanged. These findings indicate that EtPHP14 is an important molecule that can upregulate host immune response, particularly Th1, during host-parasite interaction, suggesting its importance as a novel candidate for coccidiosis vaccine.

Osteoporosis among Patients with Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-analysis of Prevalence, Severity, and Therapeutic Outcomes.

Chronic obstructive pulmonary disease (COPD) can be associated with systemic inflammatory trademarks and can coexist with other chronic debilitating diseases such as osteoporosis, which is considered among the most serious comorbidities of COPD. In this review, we aimed at finding answers for the following questions and tried to encapsulate the available literature: (1) how prevalent is osteoporosis among patients with COPD? (2) What are severity patterns of osteoporosis in case of COPD? (3) What are the therapeutic outcomes for patients with osteoporotic COPD? The total number of patients with COPD from all studies was 3815, majority of which were male (2658) representing 69.67% of patients. The mean ± standard deviation for percentage of forced expiratory volume in 1s (FEV1%) was 55.43 ± 14.62%, body mass index for almost 91.29% of patients was 24.4 ± 4.45 kg/m2, whereas fat-free mass index (FFMI) was 17 ± 0.93 kg/m2 for 17.66%. The percentage of patients with COPD having osteoporosis varied in the analyzed studies from 14% up to 66.6%. The mean prevalence of reported osteopenia from 14 studies (n = 2107) was 39.91%, whereas for osteoporosis, the mean prevalence was 37.62% for all included studies. Osteoporosis was highly prevalent among patients with COPD. It is reasonable to call for osteoporosis screening in patients with COPD who are above 65 years, in advanced stages, with BMI lower than 21 kg/m2 or with FFMI lower than 16 kg/m2 for males and 15 kg/m2 for females. There is a lack of research investigating severity and treatments of osteoporosis in patients with COPD.

Management of fractures of metacarpals and phalanges and associated risk factors for delayed healing.

OBJECTIVE: To assess the type of fractures of metacarpal and phalanges of hand and their treatment plan, investigate the risk factors (infection, segmental bone loss, associated soft tissue injuries) for the development of delayed union of the fracture site. METHODS: This descriptive study was conducted at Plastic, Reconstructive and Hand Surgery Unit, Liaquat National Hospital, Karachi. It included 120 patients who attended Accident and Emergency Department with metacarpals and phalanges fractures during August 2005 to January 2006. Severely traumatized patients or patients with amputated hand or digits were excluded. The data was collected through hand injury chart which fulfilled the inclusion criteria. Data was analyzed by SPSS version-10. RESULTS: In 120 patients with 226 fractures of the metacarpals and phalanges male to female ratio was 5:1. Metacarpal fractures were 38.9% and the fracture of the phalanges was 61.1%. Oblique fractures were 47%, transverse 28.3%, comminuted 13.27%, spiral 8.9%, and avulsion fractures were 2.6%. Surgically treated patients were 78.3% while 21.7% were managed conservatively. For fixation of fractures Kirschner wires (K-wire) were used in 89.36% cases, miniplates and lag screw in 4.25% and external fixators in 2.1%. Infection was found in 5 (2.2%) of the total fractures, out of these 2/5 (40%) had developed non union of the fracture site. Bony defect was found in 30 (13.3%) of the total fractures, of these 4/30 (13.3%) developed non union. Associated soft tissue injury was found in 130 (57.5%) and of these 11/130 (8.46%) developed non union. CONCLUSION: Most of the fractures of the metacarpals and phalanges were oblique in configuration, followed by transverse fractures. More then 75% of these fractures where treated surgically. K-wiring was the most commonly performed procedure. Infection, segmental bone loss and associated soft tissue injuries were predisposed to non union in small percentage of cases.

Gender difference in metacarpal descent of fifth metacarpal.

OBJECTIVE: To determine the difference in metacarpal descent of fifth metacarpal between men and women. STUDY DESIGN: Descriptive study. PLACE AND DURATION: The outpatient department of plastic, reconstructive and hand surgery at Liaquat National Hospital, Karachi, from August 2005 to February 2006. PATIENTS AND METHODS: Skyline of the 2nd and 3rd metacarpals were used as reference line, from which the descent of the 5th metacarpal head was measured. The position of 5th metacarpal head was documented as angle X. Metacarpal descent was defined as the difference between angle "X" in relaxed and clenched fist position. The relaxed position was standardized by placing the forearm, wrist and palm on a shaped woodblock such that the wrist would be held in 25 - 30 degree in extension by a triangular spur, supported the 3rd metacarpal only. It was ensured that the movement of 4th and 5th metacarpals were not impaired. Analysis of variance was performed to compare the significance of means between genders at p<0.05 level of significance. RESULTS: Metacarpal descent of the 5th metacarpal of both hands was significantly greater for women, with a mean of 7 degree as compared with a mean of 4 degree for the men. This decrease in angle "X" was significant for the right 5th metacarpal relaxed and fist position and the fist position on the left. In contrast, women showed no significant differences between the various age groups for any of the variables tested. There was no relationship between metacarpal descent and hand dominance. CONCLUSION: Difference in metacarpal descent between men and women is significant and must be kept in mind when hand function is evaluated in both genders to assess the outcome of treatment and rehabilitation.

Reliability of rodent animal models in biomedical research.

Despite the discrepancies observed between the data generated from humans and animals, it is a usual practice that the results obtained from animal models are extrapolated on humans. This review stresses that while animal models are essential for the research and development, a critical caution needs to be practiced in interpreting the results. Uncritical reliance on the results of animal experimentation can be dangerously misleading and has resulted in damages to human health in several cases. This review also discusses the role of certain confounding factors in using animal models due to which appropriate precautions need to be taken while deciding to conduct a study using animal models and caution is warranted in extrapolating the data obtained from pre-clinical studies on humans.

Myocardial ischaemia and reperfusion injury: reactive oxygen species and the role of neutrophil.

A growing body of evidence suggests that oxygen radicals can mediate myocardial tissue injury during ischaemia and, in particular, during reperfusion. This review focuses on the role of neutrophil as a mediator of myocardial damage. Upon reperfusion, neutrophils accumulate and produce an inflammatory response in the myocardium that is responsible, in part, for the extension of tissue injury associated with reperfusion. It has shown that the inhibition of neutrophil accumulation and adhesion is associated with decreased infarct size. This strongly suggests that myocardial cells at risk region undergo irreversible changes upon reperfusion and accumulation of neutrophils. Several pharmacological agents (ibuprofen, allopurinol, prostacyclin, and prostaglandin E analogues) protect the myocardium from reperfusion injury. In addition, the mechanisms by which these agents act and directions of research that may lead to therapeutically useful approaches are also discussed in this review.

Acute Kidney Injury Recognition and Management: A Review of the Literature and Current Evidence.

Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration.