Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach.

The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with ß-sitosterol (100 mg/kg b wt), ß-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds ß-sitosterol, ß-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.

Pneumocystis jirovecii pneumonia in a patient treated with trastuzumab-deruxtecan.

Trastuzumab-deruxtecan (T-DXd) is a novel antibody drug conjugate that has improved treatment outcomes in patients with ERBB2-positive cancer, including locally advanced or metastatic gastric and gastro-oesophageal junction adenocarcinoma. One of the reported side effects of this medication is drug-induced pneumonitis. We present in this case report, a diagnostic dilemma of a patient presenting with clinical and radiographical features of drug-induced pneumonitis but was found to have pneumocystis jirovecii pneumonia (PJP). Our case is the first of PJP in a patient treated with T-DXd, highlighting the increasing incidence of this opportunistic infection in patients with solid malignancy. It also highlights the clinical and radiographical similarities between the PJP and drug-induced pneumonitis.

A 48-Year-Old Woman With Chronic Cough, Dyspnea, and Bronchiectasis.

CASE PRESENTATION: A 48-year-old woman sought a second opinion for dyspnea and chronic productive cough; she was a never smoker. Mild respiratory symptoms persisted since childhood and had progressively worsened over the previous decade. In addition, an unintentional 30-pound weight loss had occurred over several years. Six years previously, a diagnosis of hypersensitivity pneumonitis was made following right upper lobe wedge resection that revealed chronic bronchiolitis with interstitial pneumonia and non-necrotizing granulomatous inflammation. Subsequent use of prednisone elicited mild intermittent improvement. She had used feather pillows in the past without any other significant exposures. There were no reports of sinus or GI symptoms.

Do we need to see to believe?-radiomics for lung nodule classification and lung cancer risk stratification.

Despite multiple recent advances, the diagnosis and management of lung cancer remain challenging and it continues to be the deadliest malignancy. In 2011, the National Lung Screening Trial (NLST) reported 20% reduction in lung cancer related mortality using annual low dose chest computed tomography (CT). These results led to the approval and nationwide establishment of lung cancer CT-based lung cancer screening programs. These findings have been further validated by the recently published Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) and Multicentric Italian Lung Detection (MILD) trials, the latter showing benefit of screening even beyond the 5 years. However, the implementation of lung cancer screening has been impeded by several challenges, including the differentiation between benign and malignant nodules, the large number of false positive studies and the detection of indolent, potentially clinically insignificant lung cancers (overdiagnosis). Hence, the development of non-invasive strategies to accurately classify and risk stratify screen-detected pulmonary nodules in order to individualize clinical management remains a high priority area of research. Radiomics is a recently coined term which refers to the process of imaging feature extraction and quantitative analysis of clinical diagnostic images to characterize the nodule phenotype beyond what is possible with conventional radiologist assessment. Even though it is still in early phase, several studies have already demonstrated that radiomics approaches are potentially useful for lung nodule classification, risk stratification, individualized management and prediction of overall prognosis. The goal of this review is to summarize the current literature regarding the radiomics of screen-detected lung nodules, highlight potential challenges and discuss its clinical application along with future goals and challenges.

Lung Cancer Screening: Characteristics of Nonparticipants and Potential Screening Barriers.

BACKGROUND: Patients eligible and referred for lung cancer screening (LCS) may not complete the visit. We aimed to identify differences in demographic, clinical, and socioeconomic characteristics between LCS participants and LCS-eligible nonparticipants and determine potential reasons for nonparticipation. MATERIALS AND METHODS: LCS-eligible patients referred between April 2015 and August 2016 were divided into participants and nonparticipants. Retrospective data were collected. A telephone survey was conducted in a subset of nonparticipants to identify reasons for not participating and assess their understanding of the benefits and harms of LCS. RESULTS: We identified 542 participants and 276 LCS-eligible nonparticipants. Female sex, lower pack-years, active smoking, the absence of a history of chronic obstructive pulmonary disease, coronary artery disease, or liver disease, and chronic kidney disease or a history of malignancy were associated with not participating. One hundred nonparticipants completed the telephone survey-29% were unaware of the appointment; 19% had concerns about the distance from the screening site and 14% with insurance coverage; 10% had fear of the imaging result; and 10% felt the computed tomography scan was unnecessary. Eighteen percent knew the benefit of LCS, and 69% were not aware of any screening harms. CONCLUSIONS: LCS-eligible nonparticipants are more likely to be female, active smokers, have fewer total pack-years of smoking, chronic kidney disease, a history of prior malignancy, and not have chronic obstructive pulmonary disease, coronary artery disease, or liver disease. Targeted education about the benefits and harms of LCS, verification of insurance coverage, and providing convenient screening locations may improve participation.

80-year-old man with dyspnoea and bilateral groundglass infiltrates: an elusive case of COVID-19.

COVID-19 is a novel viral infection caused by severe acute respiratory syndrome-coronavirus-2 virus, first identified in Wuhan, China in December 2019. COVID-19 has spread rapidly and is now considered a global pandemic. We present a case of a patient with minimal respiratory symptoms but prominent bilateral groundglass opacities in a 'crazy paving' pattern on chest CT imaging and a negative initial infectious workup. However, given persistent dyspnoea and labs suggestive of COVID-19 infection, the patient remained hospitalised for further monitoring. Forty-eight hours after initial testing, the PCR test was repeated and returned positive for COVID-19. This case illustrates the importance of clinical vigilance to retest patients for COVID-19, particularly in the absence of another compelling aetiology. As COVID-19 testing improves to rapidly generate results, selective retesting of patients may uncover additional COVID-19 cases and strengthen measures to minimise the spread of COVID-19.

Diagnosis and treatment of acute pulmonary inflammation in critically ill patients: The role of inflammatory biomarkers.

Pneumonia and acute respiratory distress syndrome are common and important causes of respiratory failure in the intensive care unit with a significant impact on morbidity, mortality and health care utilization despite early antimicrobial therapy and lung protective mechanical ventilation. Both clinical entities are characterized by acute pulmonary inflammation in response to direct or indirect lung injury. Adjunct anti-inflammatory treatment with corticosteroids is increasingly used, although the evidence for benefit is limited. The treatment decisions are based on radiographic, clinical and physiological variables without regards to inflammatory state. Current evidence suggests a role of biomarkers for the assessment of severity, and distinguishing sub-phenotypes (hyper-inflammatory versus hypo-inflammatory) with important prognostic and therapeutic implications. Although many inflammatory biomarkers have been studied the most common and of interest are C-reactive protein, procalcitonin, and pro-inflammatory cytokines including interleukin 6. While extensively studied as prognostic tools (prognostic enrichment), limited data are available for the role of biomarkers in determining appropriate initiation, timing and dosing of adjunct anti-inflammatory treatment (predictive enrichment).

A 31-Year-Old Man With Airflow Obstruction, Intrathoracic Adenopathy, and Pulmonary Nodules.

CASE PRESENTATION: A 31-year-old white man presented for evaluation of productive cough and dyspnea on exertion of 2 months' duration. Associated symptoms included wheezing, chest tightness, and postnasal drip. He was recently treated for pneumonia with a 7-day course of levofloxacin because of an abnormal chest radiograph demonstrating bilateral infiltrates, but his symptoms failed to improve. He had a medical history of mild intermittent asthma and was on no active treatment. He was a nonsmoker. He was born in the United States. He denied any recent travel within or outside the United States, sick contacts, or illicit drug use. He did not have any pets and denied exposure to mold, hot tubs, a down comforter, or pillows. He worked in a vocational program and his hobbies included refinishing wood floors.

Frequency of Incidental Findings and Subsequent Evaluation in Low-Dose Computed Tomographic Scans for Lung Cancer Screening.

RATIONALE: The U.S. Preventive Services Task Force recommends lung cancer screening with low-dose chest computed tomographic scans (LDCT) for a well-defined high-risk population. Data on the frequency and impact of incidental findings (IFs) based on LDCT scans performed within a centralized lung cancer screening program have not been reported. OBJECTIVES: Researchers in previous studies have reported IFs in the setting of clinical trials. We present our findings in a real clinical setting where the decision to manage these findings may depend on factors that are not captured in a research trial such as disclosing IFs, patient preferences, severity of comorbidities, and physician expertise. METHODS: We conducted a retrospective chart review of participants in the Cleveland Clinic Lung Cancer Screening Program from April 1, 2015, to February 17, 2016. Lung Imaging Reporting and Data System categories and all reported findings were extracted from the structured radiology report. Downstream investigations that occurred as a result of the imaging findings were recorded. Medicare reimbursement rates were documented for all screening-related testing and treatment. RESULTS: A total of 320 LDCT-screened patients' records were reviewed. The most commonly reported IFs were pulmonary (69.6%), cardiovascular (67.5%), and gastrointestinal (25.9%). Fifteen percent of the scans had an IF that resulted in further evaluation. The majority of patients who underwent further testing had cardiovascular findings (10.3%); less frequently, they had thyroid or adrenal nodules (2.1%), hepatic lesions (0.9%), renal masses (0.6%), or pulmonary disease (0.6%). The most frequently ordered investigations were echocardiography (n = 9), cardiac stress test (n = 9), and CT angiography (n = 6). Reimbursement for the screening process, evaluation, and treatment of screening-detected findings averaged $817 per screened patient. CONCLUSIONS: Clinically significant IFs on LDCT scans for lung cancer screening are common, and their potential impact should be included in the shared decision-making process. Screening program staff should develop a standard approach for the evaluation of these findings and consider the financial impact when seeking infrastructure support for screening program implementation.

Management of bleeding gastric varices: a single session of histoacryl injection may be sufficient.

OBJECTIVE: Gastric variceal bleeding is one of the most feared complications of portal hypertension and hence merits investigation for its optimal therapy. We aimed to evaluate the efficacy and long-term outcome(s) of patients treated with a single session of histoacryl sclerotherapy for active gastric variceal bleeding. METHODS: The medical records of patients who presented with active gastric variceal bleeding between 1998 and 2011 in a tertiary care setting were evaluated retrospectively and the eventual outcome(s) (initial hemostasis, rebleeding, and mortality rate) was assessed at least 1 year after the index bleed. RESULTS: Ninety-seven patients were included. The mean age of the patients was 51.0 ± 12.5 years; 62% were men. Hepatitis C was the most common etiology, found in 63 (65%) patients. The majority of the patients were classified as Child-Pugh grade B and C: 44 (46%) and 29 (31%) patients, respectively. A total of 40 (41%) patients were IGV1, 35 (36%) patients were GOV 2, 20 (21%) patients were GOV 1, and 2 (2%) patients were IGV2. A single session of histoacryl was successful in controlling bleeding in 83 (86%) patients. Seven (7%) patients died during the hospital stay. Rebleeding was observed in 24 (27%) patients during the 1-year follow-up, of whom 12 (50%) were managed successfully with repeated histoacryl injection. The overall mortality rate at 6 weeks, 6 months, and 1 year was 14 (14%), 19 (20%) and 26 (27%) patients, respectively. Child-Pugh classification was a significant prognostic factor of survival (P<0.001). CONCLUSION: A single session of histoacryl sclerotherapy is effective in the majority of patients with active gastric variceal bleeding. Rebleeding was observed in one-fourth of patients, half of whom were controlled successfully by repeated histoacryl sclerotherapy.

Clinical course and outcome of acute severe asthma (status asthmaticus) in adults.

OBJECTIVE: To evaluate the clinical course and outcomes in patients with acute severe asthma in a tertiary care setting. METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of patients of age 16 and above who were admitted with a diagnosis of acute severe asthma from January 2000 to December 2013. These patients had undergone clinical evaluation to assess the severity of illness as well as the complications and eventual outcomes. SPSS 16 was used for statistical analysis. RESULTS: Of the 50 patients in the study, 41 (82%) were females. The overall mean age was 53.1±20.3 years. Ventilator support was required by 37(74%) patients. Presence of acidaemia was associated with the need for invasive ventilation (p<0.033) which in turn was associated with increased hospital stay (p<0.043). Complications were observed in 37(74%) patients, the most common being respiratory failure in 35(70%) and arrhythmias in 8(16%). Use of both non-invasive and invasive ventilation was found to be significantly associated with development of complications (p<0.001 and p<0.009). A total of 4(8%) patients died. Presence of acidaemia was found to be significantly associated with mortality (p<0.032). CONCLUSION: Overt acidaemia at initial presentation in patients with acute severe asthma was significantly associated with higher rates of invasive ventilation leading to increased hospital stay, complications and higher mortality rate.

Clinically significant contrast induced acute kidney injury after non-emergent cardiac catheterization--risk factors and impact on length of hospital stay.

OBJECTIVE: To evaluate the frequency and risk factors associated with clinically significant contrast-induced nephropathy (CIN) in patients undergoing non-emergent coronary angiography. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 2005 to December 2007. METHODOLOGY: Case records of patients who underwent coronary angiography with a serum creatinine of 1.5 mg/dl at the time of procedure were evaluated. Clinically significant contrast induced nephropathy (CSCIN) was defined as either doubling of serum creatinine from baseline value within a week following the procedure or need for emergency hemodialysis after the procedure. RESULTS: One hundred and sixteen patients met the inclusion criteria. Mean age was 64.0 ± 11.5 years, 72% were males. Overall prevalence of CIN was 17% (rise of serum creatinine by ≥ 0.5 mg/dl) while that of clinically significant CIN (CSCIN) was 9.5% (11 patients). Patients with CSCIN had significantly lower left ventricular ejection fraction (p = 0.03, OR: 0.24; 95% CI = 0.06 - 0.91) and higher prevalence of cerebrovascular disease (p < 0.001, OR: 14.66; 95% CI = 3.30 - 65.08). Mean baseline serum creatinine was significantly higher, 3.0 ± 1.5 vs. 2.0 ± 1.1 mg/dl (p = 0.03, OR: 1.47; 95% CI = 1.03 - 2.11) whereas mean GFR estimated by Cockcroft-Gault formula was significantly lower at 25 ± 7.4 vs. 41.0 ± 14.6 ml/minute (p = 0.001, OR = 0.89, 95% CI = 0.84 - 0.95) at the time of procedure in patients with CSCIN. Mean length of hospital stay was significantly higher in this group compared to those without CIN, 9.0 ± 5.1 vs. 3.0 ± 3.2 days (p = 0.001, OR = 1.31, 95% CI = 1.12 - 1.54). Multivariate analysis revealed low GFR (p = 0.001, OR = 0.88; 95% CI = 0.82 - 0.95) and low ejection fraction (p = 0.03, OR = 0.20; 95% CI = 0.04 - 0.91) to be independent factors associated with CSCIN. No significant differences were noted between the two groups in patients with hypertension, diabetes and heart failure. CONCLUSION: CSCIN is a significant concern in high risk groups despite prophylaxis. Patients with lower EF, cerebrovascular disease and low GFR at the time of procedure are more likely to have CIN.

Sleep duration and breast cancer phenotype.

Emerging evidence suggests that short sleep is associated with an increased risk of cancer; however, little has been done to study the role of sleep on tumor characteristics. In this study, we evaluated the relationship between sleep duration and tumor phenotype in 972 breast cancer patients. Sleep duration was inversely associated with tumor grade (univariate P = 0.032), particularly in postmenopausal women (univariate P = 0.018). This association did not reach statistical significance after adjustments for age, race, body mass index, hormone replacement therapy use, alcohol consumption, smoking, and physical activity in the entire study sample (P = 0.052), but it remained statistically significant (P = 0.049) among post-menopausal patients. We did not observe a statistically significant association between sleep duration and stage at diagnosis, ER, or HER2 receptor status. These results present a modest association between short duration of sleep and higher grade breast cancer in post-menopausal women. Further work needs to be done to validate these findings.

A rare aetiology of respiratory failure in a 10-year-old boy: inflammatory myofibroblastic tumour.

Primary neoplasms of the respiratory tract are rarely encountered in the paediatric population. Inflammatory myofibroblastic tumour (IMT) is a rare soft tissue mesenchymal tumour but a distinct disease entity accounting for less than 1% of all primary lung tumours. We report a case of a 10-year-old boy who presented with respiratory failure and left lung collapse. On flexible fiberoptic bronchoscopy, a pedunculated mass in the lower part of the trachea originating from the left main stem bronchus was identified. The patient subsequently underwent a left-sided pneumonectomy with complete resection of the mass. The histopathological analysis was consistent with IMT. Two years of follow-up and the patient remains well.

Wilson's disease in pregnancy: case series and review of literature.

BACKGROUND: Wilson's disease is a rare, autosomal recessive inherited disorder characterized by impaired liver metabolism of copper leading to decreased biliary excretion and incorporation of ceruloplasmin levels mainly in the liver and brain. Untreated Wilson's disease has been shown to cause subfertility and even in cases where pregnancy occurs, it often results in spontaneous miscarriage. CASE PRESENTATIONS: We present four cases of successful pregnancy outcomes in three patients diagnosed with Wilson's disease along with the literature review. All the patients were managed with zinc sulphate without any postnatal complications. CONCLUSION: Patients with Wilson's disease receiving regular treatment who remain asymptomatic are usually able to conceive and achieve successful outcomes. However, these pregnancies should be considered high risk and merit regular surveillance.

How well can physicians manage tuberculosis? A public-private sector comparison from Karachi, Pakistan.

BACKGROUND: Tuberculosis (TB) is endemic in Pakistan which ranks fifth amongst the twenty two countries designated to be highly burdened by TB according to the World Health Organization. However, there is paucity of data regarding the knowledge of diagnosis of TB and its management amongst public and private practitioners. In this study, we endeavor to identify this gap in knowledge regarding the diagnosis and management of TB between public and private doctors and the factors affecting these knowledge scores in urban Pakistan. METHODS: This cross sectional survey was conducted between June and December 2011. Doctors from public hospitals, private hospitals and private clinics scattered in all eighteen towns of Karachi were included in the study. Qualified MBBS doctors working in any specialty were eligible to participate whereas doctors working in both the public and private sectors were excluded from the study. Vignette based clinical scenarios were given to assess the knowledge score regarding the diagnosis and management of TB. RESULTS: A total of 196 doctors participated in the study. There was a significant difference between private and public physicians in terms of age and years of practice (p-value <0.05). Significant differences in the proportion of knowledge scores were observed between the public and private doctors and National TB Control Program trained and untrained doctors in Karachi. Factors associated with inadequate knowledge scores were being female gender [OR: 2.76 (95% CI: 1.418-5.384)], private employment status [OR: 1.50 (95% CI: 1.258-2.439)], and not trained by NTP [OR: 2.98 (95% CI: 1.286-3.225)] on multivariate logistic regression analysis. CONCLUSION: It is concluded that a knowledge gap exists between the public and private doctors in Karachi. Strengthening of currently implemented public private mix model along with improvement in the trainings of public and private practitioners is highly recommended to control TB in Pakistan.

Patient communication in radiology: current status of breaking bad news among radiologists and radiology trainees in Pakistan.

Breaking bad news can be an intimidating task for any physician. The aim of this study was to record the practices of breaking bad news to the patients by Pakistani radiologists and trainees. The radiologists and trainees attending the 26th National Radiological Conference in October 2010 in Karachi, Pakistan, were surveyed. The response rate was 76%. The respondents included residents (51%), private practicing radiologists (28%), academic radiologists (13%), and other trainees (8%). Most of the academic radiologists communicated with their patients. The daily frequency of breaking bad news by residents was noted, which was highest in the public teaching hospitals (71%). For severe abnormalities such as malignancy, 50% residents, 55% of the academic radiologists and 74% of the private practicing radiologists were very uncomfortable in disclosure of results. Differences in frequency of communication with patients were noticed with both different training levels, and different settings of practice in a developing country.

Benign granulomatous polyp obstructing the bronchus.

Inflammatory endobronchial polyps are rarely encountered. We report a case of a 14 years old girl with a benign granulomatous polyp originating in the bronchus. Computed tomography scan showed an intraluminal soft tissue opacity while fiberoptic bronchoscopy revealed a large soft tissue mass completely occluding the left lower lobe. Rigid bronchoscopy under general anaesthesia identified a fleshy mass in the left main stem bronchus which was excised via bronchoscopy. The histopathology showed benign polyp with non-specific inflammation. The patient's symptoms improved subsequently and no recurrence was reported till two years of follow-up.

Coronary calcium scoring: are the results comparable to computed tomography coronary angiography for screening coronary artery disease in a South Asian population?

BACKGROUND: The need of having feasible screening tools like Coronary Calcium Scoring (CCS) and CT Coronary Artery (CTCA) for Coronary Artery Disease (CAD) has become paramount. We aimed to evaluate the accuracy of CCS in determining the degree of stenosis of coronary vessels as compared to that determined by CTCA in a South Asian population. METHODS: A retrospective study was conducted at The Aga Khan University Hospital. A total of 539 patient records were reviewed who had undergone CCS and CTCA between 2008 and 2010. Patient records were reviewed by comparing their CCS and CTCA results. RESULTS: About 268 out of 301 (89%) patients with a CCS of 0-9 were found to be free of stenosis on CTCA. On a CCS of 10-99, 110 out of 121 (91%) patients were either free of stenosis or had mild stenosis. About 66 out of 79 (84%) patients had moderate or severe stenosis with a calcium score of 100-400 while none of the patients were free of stenosis. Around 28 out of 38 (74%) patients with a CCS of more than 400 had severe stenosis. However, only 04 patients (11%) were found to have mild stenosis. Spearman's rho revealed a correlation coefficient of 0.791 with a p-value of <0.001. CONCLUSION: Our study reaffirms that in South Asian population, low CCS (<100) is associated with no or minimal stenosis while high CCS warrants further investigation; hence, making it a reliable tool for screening patients with CAD.