Digital eye strain and its associated factors among radiology physicians in Pakistan: a cross-sectional survey using logistic regression analysis.

Background and aims: Increased use of digital devices in the modern era has led to the development of digital eye strain (DES) or computer vision syndrome in their users. This can result in the development of various ocular and visual symptoms among them. In this study, the authors aimed to view the prevalence of digital eye strain among radiology physicians in Pakistan and their associated risk factors. Materials and methods: A cross-sectional study was conducted to evaluate occupational DES among radiology physicians in Pakistan. The data collection was done using the convenience sampling technique, and the data were analyzed using IBM SPSS for Windows, Version 25.0. Results: Out of the 247 respondents, 33.6% were males and 66.4% were females. 41.7% of them were between 30 and 40 years of age and 51.8% of them were radiology residents. 52.2% of the participants had a refractive error and were using a corrective lens. The majority of the radiologists in our study (84.2%) preferred picture archiving and communication system (PACS) over films and 82.2% of them reported having breaks of less than 15 min. Major symptoms reported by the participants were tired or heavy eyes (69.6%) and headache (69.3%). The proportion of developing DES was higher in females [P=0.001, adjusted odds ratio (aOR)=2.94], radiology residents (P=0.031, aOR=3.29), and working hours of more than 4 h per day (P<0.001, aOR=0.04). Conclusion: With recent advances in the field of radiology in Pakistan, the frequency of developing DES among radiologists is increasing. Being a female, having long working hours, and having noticeable flickers on the digital screens were among the significant factors in developing DES among radiologists.

Consanguineous marriages increase the incidence of recurrent tuberculosis: Evidence from whole exome sequencing.

BACKGROUND: In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases. METHODOLOGY: First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed. RESULTS: The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rß1. Exon 7 of the IL-12Rß1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function. CONCLUSION: Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rß-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rß1, TYK2, or JAK2 in IFN-γ production, warranting further investigation.

Infective Endocarditis Complicated by Iatrogenic Intracranial Hemorrhage Secondary to Cefazolin-Induced Coagulopathy.

Infective endocarditis can be acute or subacute. It can be caused by viral, bacterial, fungal, and sometimes nonbacterial etiologies. It is an important cause of mortality and morbidity in children as well as adolescents, despite advances in management. A 59-year-old male with a past medical history of aortic valve (AV) replacement on warfarin presented to the Emergency Department with dull right flank pain and poor dentition on examination. Computerized tomography (CT) scans of the abdomen revealed the presence of splenic and renal infarcts. Warfarin was held after the international normalized ratio (INR) was noted to be elevated at 11. Following the activation of the sepsis bundle in the ER, he received intravenous fluids (30 cc/kg) and was started on vancomycin and ceftriaxone. On further evaluation, the transesophageal echocardiogram revealed mobile densities on the aortic surface concerning vegetation. Antibiotics were transitioned to cefazolin, gentamycin, and rifampin for the management of prosthetic valve endocarditis. The patient's INR improved to 3.5 on the third day of hospitalization, and heparin was initiated to maintain anticoagulation for the prosthetic valve. However, on the eighth day of hospitalization, the patient developed left-sided weakness and slurred speech. The CT head showed acute frontoparietal intracranial hemorrhage (ICH), with an INR noted to be 5. Heparin was reversed with protamine sulfate, and vitamin K was administered, following which the INR improved to 2.3. The patient was transferred to intensive care, but on the second day of the ICU stay, the INR again shot up to 6 with normal LFTS. The patient received vitamin K, but the INR only improved to 5. Subsequently, antibiotics were changed from cefazolin to nafcillin. INR thus fell to 1.6 in two days after changing the antibiotics. The patient was soon transferred to a higher center for aortic valve replacement. While few case reports have described severe coagulopathy induced by cefazolin, it is particularly seen with impaired renal function; however, our patient's renal function was completely normal. Coagulopathy is due to the drug's effect on intestinal flora and its structural methyl-thiadiazole side chain, which has similar effects as epoxide reductase inhibitors and results in INR elevation. Patients on cefazolin need to be closely monitored for INR levels every day, as there is a high likelihood of developing complications like ICH, as noted in this patient. While the monitoring of cefazolin levels is not necessarily indicated, it is necessary to place patients on fall precautions and monitor INR levels every day, as mentioned above.

Systemic AL amyloidosis: current approach and future direction.

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

When Hormones are Being Difficult: A Rare Case and the Literature Review of Pembrolizumab-Induced Polyendocrinopathy.

Immune Checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, and ipilimumab are monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4) or program death (PD)1 and its ligand PDL1. Agents targeting PD1, such as pembrolizumab, have shown widespread efficacy in the past and are also associated with a wide range of immune-related adverse events (irAEs), including endocrine toxicities. A 31-year-old female with a medical history significant for Stage IIb Breast cancer on chemo and immunotherapy (pembrolizumab) presented with nausea, vomiting, and generalized abdominal pain. Laboratory studies showed a blood glucose level of 356 mg/dl, elevated Anion gap 18 meq/L, beta-hydroxybutyrate 46 mg/d, and low C-peptide levels <0.10 ng/ml. The patient was treated for Diabetic Ketoacidosis (DKA). Further testing revealed high Thyroid Stimulating Hormone (TSH) levels along with elevated thyroid peroxidase levels of 38 IU/L. After discharge from the hospital on insulin and levothyroxine therapy, the patient reported increasing fatigue and further testing revealed low cortisol levels <0.5 mcg/dl with elevated ACTH consistent with primary adrenal insufficiency. The patient was started on hydrocortisone therapy with improvement in symptoms. Endocrine toxicities are not uncommon in patients receiving pembrolizumab, but polyendocrinopathy in a relatively rare side effect of pembrolizumab. Only a few cases of pembrolizumab-induced polyendocrinopathy have been reported so far which we have mentioned in this article. While patients are on immunotherapy, close monitoring for clinical signs & symptoms can lead to an early diagnosis, substantially improving morbidity and mortality.

When Blood Is Being Difficult: Clotting and Bleeding in a Patient With Antiphospholipid Antibody Syndrome and Supratherapeutic International Normalized Ratio.

Venous thromboembolism includes deep venous thrombosis (DVT) and pulmonary embolism and is the most common cardiovascular disease after coronary artery disease and stroke. Antiphospholipid syndrome (APS) is an autoimmune disorder that is characterized by venous or arterial thrombosis with laboratory evidence of antiphospholipid antibodies. Long-term anticoagulation therapy is required to prevent recurrent DVTs, embolisms, and thrombosis-related complications. Treatment options include vitamin K antagonists, subcutaneous low-molecular-weight heparin, unfractionated heparin, or direct oral anticoagulants. Warfarin (a vitamin K antagonist) remains the mainstay of treatment in APS patients with a prior history of DVT and is associated with elevation of the international normalized ratio which is often used as a marker for therapy appropriateness and warfarin dosing. Here, we describe a unique case of a 65-year-old female with APS on warfarin (given prior lower extremity DVT) presenting with bleeding/hematoma in the left breast and a clot in the left upper extremity.

Design of active fault-tolerant control system for Air-fuel ratio control of internal combustion engines using fuzzy logic controller.

BACKGROUND: Fault-Tolerant Control Systems (FTCS) are used in critical and safety applications to improve performance and stability despite failure modes. As a result, costly production losses related to unusual and unplanned shutdowns can be prevented by incorporating these systems in the critical process plant machines. The Internal Combustion (IC) engines are highly used process plant machines and faults in their sensors will cause their shutdown instigating the need to install FTCS in them. INTRODUCTION: In this paper, an Active Fault-Tolerant Control System (AFTCS) based on a Fuzzy Logic Controller (FLC) is suggested to improve the reliability of the Air-Fuel Ratio (AFR) control system of an IC engine. METHODOLOGY: For analytical redundancy, a nonlinear Fuzzy Logic (FL) based observer is implemented in the proposed system for the Fault Detection and Isolation (FDI) unit for nonlinear sensors of the AFR system. Lyapunov stability analysis was used for designing a stable system in both faulty and normal conditions. To evaluate its performance, this system was developed in the MATLAB/Simulink platform. RESULTS: The simulation results show that the developed system is robust under sensor fault conditions, retaining stability with a minimum decrease of AFR. This study's comparison with the existing literature demonstrates that the proposed system is effective for maintaining the AFR in IC engines during sensor faulty conditions thus reducing shutdown of engine and production loss for increased profits.

Patterns of Hepatocellular Carcinoma After Direct Antiviral Agents and Pegylated-Interferon Therapy.

INTRODUCTION:  The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). METHODS:  A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. RESULTS:  The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. CONCLUSION:  Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.

Social Stigmatization of Drug Abusers in a Developing Country: A Cross-Sectional Study.

INTRODUCTION:  Stigma is a label that differentiates a person from others and associates them with unenviable attributes. There are various forms of stigma: enacted stigma, perceived stigma, and self-stigma manifesting as stereotyping and harboring negative thoughts about the stigmatized group. Stigmatization of the drug abuser leads to effects such as low self-esteem, depression, and personality changes in the stigmatized.  Objectives: The purpose of the study is to know the impact of stigma on patients receiving substance abuse treatment in the Psychiatry Department, Mayo Hospital Lahore, Pakistan. DESIGN: Cross-sectional study.  Place: Psychiatry Department, Mayo Hospital, Lahore, Pakistan Study Period: Six months (February 22, 2020, to July 18, 2020). SUBJECTS AND METHODS: A population-based cross-sectional study was conducted in a tertiary care hospital. A total of 100 patients were recruited in the study. The selection was made on laid down criterion after taking due consent. Interviews were conducted through a pretested questionnaire. Data were collected, compiled, and analyzed through SPSS version 20 (IBM Corp., Armonk, USA), and relevant frequency tables were drawn.  Results: On analyzing the data, various forms of stigma were observed: enacted stigma (81% as considered less capable), perceived stigma (99% as having difficulties in the job seeking and relationships), and self-stigma (94% in having devaluation thoughts). Self-esteem was maintained (73% were content). Social support was present (76% from family). Moderate depression was seen in 17% of participants. Over 83% of our study population is aged 21 to 40 years, 15% between ages 41 and 60 years, and only 2% ranging between ages 1 and 20. A total of 80% of the population belonged to a low socioeconomic status, and 55% of participants abused opium, heroin, or brown sugar, followed by white crystal use in 37% of the study population. The majority reported the drug abuse duration of 1-5 years (70%). CONCLUSION:  Stigma in its various forms affects the drug abuser undergoing treatment. It results in low self-esteem and mild depression. Individuals from the broader socioeconomic range can be added in future studies, and a larger population can be studied by collecting data from other tertiary care hospitals and mental healthcare facilities. They can be assessed for factors contributing to their addiction and the challenges they had to go through to get the help they needed.