Hypomagnesaemia in Acute Exacerbation Chronic Obstructive Airway Disease; Association with Anthonisen’s Levels of Exacerbation

Background: COPD is major public health issue causing morbidity and mortality. Lower serum magnesium levels are seen in patients with acute exacerbations compared to stable COPD patients. This study aims at identifying hypomagnesemia as predictor of COPD exacerbations that may help reduce the burden of readmissions and mortality. Material and Methods: The Descriptive cross-sectional study was conducted –removed for blind review---from 16 July 2016 to 15 Jan 2017 after the ethical approval and informed consent. The indoor adult (>18years) diagnosed cases of COPD exacerbation were included by consecutive sampling. Patients with malignancy, pregnancy and receiving magnesium supplements were excluded.  Demographic details documented and after complete clinical evaluation, serum Magnesium levels of were assessed. Serum Magnesium < 1.80 mg/dl labeled hypomagnesaemia.  Data was analyzed by SPSS with significant p< 0.05. Results: Amongst 176 patients; there were 93(52.8%) males and 83(47.2%) females. Mean age was 56+7 years. Mean duration of COPD was 6.56 + 5.24 years (2-10 years).  Mean height in the study was 181 +12 cm and mean weight was 56.06 + 7.08 kg. The mean serum magnesium level was 1.5 + .49mg/dl. Low serum magnesium (<1.8 mg/dl) observed in 103(58.5%), gender wasn’t associated with hypomagnesaemia (p=0.294). Hypomagnesaemia in accordance to types of Anthonisen’s criteria was observed in 19(44.2%) with Type I, 37(57.8%) with Type II and 47(68.1%) with Type III COPD exacerbation. Hypomagnesaemia had significant association with Anthinosen’s levels of exacerbation (p=0.043). The mean age in patients with hypomagnesaemia was 56.61+6.78 Vs.  55.30+7.47 in patients without hypomagnesaemia (p=0.228). Conclusion: The study concludes mean serum magnesium levels are significantly lower in patients with acute exacerbation of COPD (58.5%), particularly in type II and III. Magnesium levels should be performed in all COPD exacerbations irrespective of gender and age. Replacement of magnesium may be helpful in alleviating symptoms and reducing frequency of exacerbations. KEYWORDS:   COPD.   Acute exacerbation.  Serum Magnesium levels. Hypomagnesaemia

Hypomagnesaemia in Acute Exacerbation Chronic Obstructive Airway Disease; Association with Anthonisen’s Levels of Exacerbation

Background: COPD is major public health issue causing morbidity and mortality. Lower serum magnesium levels are seen in patients with acute exacerbations compared to stable COPD patients. This study aims at identifying hypomagnesemia as predictor of COPD exacerbations that may help reduce the burden of readmissions and mortality. Material and Methods: The Descriptive cross-sectional study was conducted –removed for blind review---from 16 July 2016 to 15 Jan 2017 after the ethical approval and informed consent. The indoor adult (>18years) diagnosed cases of COPD exacerbation were included by consecutive sampling. Patients with malignancy, pregnancy and receiving magnesium supplements were excluded.  Demographic details documented and after complete clinical evaluation, serum Magnesium levels of were assessed. Serum Magnesium < 1.80 mg/dl labeled hypomagnesaemia.  Data was analyzed by SPSS with significant p< 0.05. Results: Amongst 176 patients; there were 93(52.8%) males and 83(47.2%) females. Mean age was 56+7 years. Mean duration of COPD was 6.56 + 5.24 years (2-10 years).  Mean height in the study was 181 +12 cm and mean weight was 56.06 + 7.08 kg. The mean serum magnesium level was 1.5 + .49mg/dl. Low serum magnesium (<1.8 mg/dl) observed in 103(58.5%), gender wasn’t associated with hypomagnesaemia (p=0.294). Hypomagnesaemia in accordance to types of Anthonisen’s criteria was observed in 19(44.2%) with Type I, 37(57.8%) with Type II and 47(68.1%) with Type III COPD exacerbation. Hypomagnesaemia had significant association with Anthinosen’s levels of exacerbation (p=0.043). The mean age in patients with hypomagnesaemia was 56.61+6.78 Vs.  55.30+7.47 in patients without hypomagnesaemia (p=0.228). Conclusion: The study concludes mean serum magnesium levels are significantly lower in patients with acute exacerbation of COPD (58.5%), particularly in type II and III. Magnesium levels should be performed in all COPD exacerbations irrespective of gender and age. Replacement of magnesium may be helpful in alleviating symptoms and reducing frequency of exacerbations. KEYWORDS:   COPD.   Acute exacerbation.  Serum Magnesium levels. Hypomagnesaemia

Severity Index and Outcome of Hospitalized COVID-19 Patients in Capital Hospital, CDA, Islamabad

Objective: To assess clinical characteristics and outcome of patients with Covid-19 infection. Study design: Descriptive cross-sectional study.Place and duration of study: Department of Medicine, Capital Hospital Islamabad from February 01, 2021 to April 25, 2021.Methodology: A manual medical record of total of 221 patients was conducted, more than 18 years of age, both genders, who presented with features suggestive of Covid-19 infection were included. Patients were tested for COVID-19 PCR, blood complete picture and inflammatory markers. The data was analyzed by using SPSS version 42.Results: Among 221 patients, there were 125(56.6%) males and 96(43.4%) females. Mean age was 57.20+13.17 years. Total 155(70%) cases were Covid PCR +ve and 66(30%) –ve. 86(38.9%) cases had mild, 91(41.2%) had moderate and 44(19.9%) had severe covid-19 infection. Lymphopenia was observed in 154(69.7%) cases. C-reactive protein was positive in 178(80.5%) cases. Serum ferritin was raised in 114(51.5%) cases, D-dimers in 139(66.9%), lactic dehydrogenase in 167(75.5%) cases with significant association with disease severity. Serum interleukin, performed in moderate and severe cases only, had mean value of 54.1+105.94pg/ml. Diabetes mellitus was found significantly associated with mortality (p=0.007) as well as hypertension (p<0.0001). 207 cases were managed and discharged, 14 cases expired (6.33%). Mortality was significantly associated with disease severity (p<0.001). Remdesivir was given to symptomatic patients and 94.4 % patients were discharged vs 5.6 % expired. Remdesivir and tocilizumab was given in combination in severe/critical patients and 76.5% patients were discharged vs 23.5% expired.Conclusion: Covid-19 is a disease with variable presentations. Severity of Covid-19 infection is directly related to lymphopenia as well as inflammatory markers. IL-6 levels, raised in more severe cases, signify immune response to Covid-19. Disease is more severe in patients with comorbids. In moderate to severe disease remdesivir and in severe covid disease with high IL-6 levels combination of antiviral and tocilizumab may help to improve outcome

NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines

<p>Abstract</p> <p>Background</p> <p>YB-1 is a multifunctional protein that affects transcription, splicing, and translation. Overexpression of YB-1 in breast cancers causes cisplatin resistance. Recent data have shown that YB-1 is also overexpress in colorectal cancer. In this study, we tested the hypothesis that YB-1 also confers oxaliplatin resistance in colorectal adenocarcinomas.</p> <p>Results</p> <p>We show for the first time that transfection of YB-1 cDNA confers oxaliplatin resistance in two colorectal cancer cell lines (SW480 and HT29 cell lines). Furthermore, we identified by mass spectrometry analyses important YB-1 interactors required for such oxaliplatin resistance in these colorectal cancer cell lines. A tagged YB-1 construct was used to identify proteins interacting directly to YB-1 in such cells. We then focused on proteins that are potentially involved in colorectal cancer progression based on the Oncomine microarray database. Genes encoding for these YB-1 interactors were also examined in the public NCBI comparative genomic hybridization database to determine whether these genes are localized to regions of chromosomes rearranged in colorectal cancer tissues. From these analyses, we obtained a list of proteins interacting with YB-1 and potentially involved in oxaliplatin resistance. Oxaliplatin dose response curves of SW480 and HT29 colorectal cancer cell lines transfected with several siRNAs corresponding to each of these YB-1 interactors were obtained to identify proteins significantly affecting oxaliplatin sensitivity upon gene silencing. Only the depletion of either NONO or RALY sensitized both colorectal cancer cell lines to oxaliplatin. Furthermore, depletion of NONO or RALY sensitized otherwise oxaliplatin resistant overexpressing YB-1 SW480 or HT29 cells.</p> <p>Conclusion</p> <p>These results suggest knocking down NONO or RALY significant counteracts oxaliplatin resistance in colorectal cancers overexpressing the YB-1 protein.</p

STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma

Background Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer characterized by complex aberrant genomes. A fundamental goal of current studies is to identify those somatic events arising in the variable landscape of PDA genomes that can be exploited for improved clinical outcomes. Methods We used DNA content flow sorting to identify and purify tumor nuclei of PDA samples from 50 patients. The genome of each sorted sample was profiled by oligonucleotide comparative genomic hybridization and targeted resequencing of STAG2. Transposon insertions within STAG2 in a KRASG12D-driven genetically engineered mouse model of PDA were screened by RT-PCR. We then used a tissue microarray to survey STAG2 protein expression levels in 344 human PDA tumor samples and adjacent tissues. Univariate Kaplan Meier analysis and multivariate Cox Regression analysis were used to assess the association of STAG2 expression relative to overall survival and response to adjuvant therapy. Finally, RNAi-based assays with PDA cell lines were used to assess the potential therapeutic consequence of STAG2 expression in response to 18 therapeutic agents. Results STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon-mediated disruption of STAG2 in a KRASG12D genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (>95% of nuclei positive) was associated with a median survival benefit of 6.41 months (P = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; P = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally, we show that RNAi-mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy. Conclusions Based on these iterative findings we propose that STAG2 is a clinically significant tumor suppressor in PDA