COVID-19-associated Coagulopathy and Thromboembolism: Determination of Their Patterns and Risk Factors as Predictors of Mortality Among Severe COVID-19 Patients.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is associated with Coagulopathy (CAC) and Venous Thromboembolism (VTE). These are well-reported complications of COVID-19 infection. Earlier publications have shown that CAC and thromboembolism are predictors of mortality among COVID-19 patients with severe disease. MATERIALS AND METHODS: A prospective study was conducted in the Intensive Care Unit (ICU) where all confirmed COVID-19 patients were enrolled and followed until death or ICU discharge. CAC, VTE, along with all comorbidities, were recorded. Predictors of mortality were determined by univariate and multivariate regression. RESULTS: Among 261 patients with COVID-19, 48.3% survived and 51.7% died. CAC was present in 53.2% and 76.3% of the survivors and non-survivors, respectively (p<0.001); 89 patients (31.4%) had VTE (p=0.36) and 11 patients (4.2%) had arterial thrombosis (p=0.76) among survivors and nonsurvivors. Age between 71-80 years (p=0.009), male gender (p=0.045), CAC (p<0.001), comorbidities like chronic kidney disease (CKD, p=0.013), chronic obstructive pulmonary disease (COPD, p=0.001) and asthma (p=0.046), were significant predictors of mortality. CONCLUSION: A severe complication of COVID-19 is CAC, such as sepsis-induced coagulopathy, overt disseminated-coagulopathy and VTE. Old age, various comorbidities (e.g., COPD, CKD, or asthma), CAC, VTE (pulmonary embolism) and coagulation parameters with critical severity score (D-dimers, platelets, prothrombin time) and the SOFA (Sequential Organ Failure Assessment) score were significant predictors of mortality among COVID-19 patients.

The Neuro-Vascular Consequence of Diabetes: Foot Amputation and Evaluation of its Risk Factors and Health-Related Economic Impact.

BACKGROUND: The rising prevalence of type 2 diabetes mellitus (T2DM) with the huge burden of diabetic foot amputation is a challenge to the health economy of Pakistan and other countries. Identification of various risk factors for amputation, along with its financial burden, is needed to address this problem. OBJECTIVES: This study aimed to determine the financial burden and risk factors associated with T2DMrelated foot amputation. METHODS: Retrospective hospital-based study from January 2017 to December 2018. Patients with T2DM with and without amputation were enrolled. The direct medical costs of amputation along with various risk factors, were determined. Risk factors were evaluated by logistic regression analysis. RESULTS: A total of 1460 patients with T2DM were included; 484 (33%) patients had an amputation. The mean total cost of below knee, fingers and toe amputation was 886.63±23.91, 263.35 ±19.58 and 166.68 ± 8.47 US$, respectively. This difference among groups was significant (p<0.0001). Male gender (odds ratio, OR: 1.29, 1.01-1.63, p=0.037), peripheral artery disease (OR: 1.93, 1.52-2.46, p=0.000), peripheral neuropathy (OR: 1.31, 1.40-1.63, p=0.000), prior diabetic foot ulcer (OR: 2.02, 1.56- 2.56, p=0.000) and raised glycated haemoglobin (HbA1c) (OR: 3.50, 2.75-4.4, p=0.000) were risk factors for amputation. CONCLUSION: The health-related financial impact of amputations is high. Peripheral artery disease, peripheral neuropathy, prior diabetic foot ulcer and raised HbA1c were risk factors for amputation.

Restless Leg Syndrome in Patients with Liver Cirrhosis! Its Frequency, Severity, and Correlation.

BACKGROUND: Restless leg syndrome (RLS) has been recognized as a typical additional manifestation among patients with cirrhosis of the liver. RLS prevalence in liver cirrhosis further worsens the quality of life, which has already been compromised with the disease-related complications of cirrhosis itself. AIMS: The study aimed to determine the frequency and severity of Restless Leg Syndrome (RLS) among patients with cirrhosis of the liver and to correlate its severity with the severity of cirrhosis. METHODS: This prospective cross-sectional study was carried out at Ruth K.M. Pfau Civil Hospital (Karachi, Pakistan) from December 2019 to February 2020. Three hundred and fifteen cirrhotic patients with any etiology were included in the study after informed written consent. Restless leg syndrome with its severity was determined in all cirrhotic patients. For continuous variables, means and medians with standard deviations were calculated, while percentages and proportions were used for discrete variables. Spearman correlation was used to find significance between RLS Severity Score (RSS) and Model of End-stage Liver Disease MELD Score. A p value of < 0.05 was considered significant for all analyses. RESULTS: The frequency of RLS among cirrhotic patients was 38.4%. More than half (54.5%) of the patients had severe RLS. Viral related hepatitis C and hepatitis B were the most common cause of cirrhosis of the liver (57.8% and 30.8%). A significant difference was found between as patients both with or without RLS in terms of age (p=0.003), gender (p=0.005), hemoglobin (p=0.00), and serum albumin (p=0.01). No significant association was found between RLS severity score and MELD Score (p=0.693). CONCLUSION: Prevalence of RLS is very high among cirrhotic patients, but no correlation was found between the severity of RLS and cirrhosis. Further studies should be carried out to assess the quality of life in cirrhotic patients having RLS.

Haemorrhagic versus non haemorrhagic ascites in cirrhosis: Their relationship and impact on prognosis of liver cirrhosis.

OBJECTIVES: To evaluate the impact of haemorrhagic ascites on prognosis of patients with advance cirrhosis, this study was further aimed to assess the relationship between haemorrhagic ascites and advance cirrhosis and its effect on prognosis. METHODS: Eight hundred and thirty-eight patients having liver cirrhosis with ascites were analyzed retrospectively (over three years) while segregated into two groups haemorrhagic and non haemorrhagic ascites. Patient outcome variables were identified among both groups and independent predictors for survival were analyzed. Kaplan-Meier survival estimates determined survival rate comparison between groups. RESULTS: Haemorrhagic ascites was detected in (26.6%) patients. Spontaneous haemorrhagic ascites(79%) was the main cause of haemorrhagic ascites followed by hepatocellular carcinoma (14%) and iatrogenic (7.6%). Spontaneous bacterial peritonitis and acute kidney injury were statistically significant (p= 0.0001, 0.0001) among groups. Overall mortality at year three was higher (83%) in haemorrhagic ascites group. Survival among both groups (haemorrhagic versus non haemorrhagic) at one month, one year and three year was found to be significant (p= 0.000, 0.000 and 0.000). CONCLUSION: Haemorrhagic ascites impact overall survival with more mortality in comparison to non haemorrhagic ascites. Haemorrhagic ascites was an independent predictor of survival. Haemorrhagic ascites is possibly considered another predictor of survival among advance cirrhosis.

Covalent immobilization of luminescent oxygen indicators reduces cytotoxicity.

Luminescence-based oxygen sensing is a widely used tool in cell culture applications. In a typical configuration, the luminescent oxygen indicators are embedded in a solid, oxygen-permeable matrix in contact with the culture medium. However, in sensitive cell cultures even minimal leaching of the potentially cytotoxic indicators can become an issue. One way to prevent the leaching is to immobilize the indicators covalently into the supporting matrix. In this paper, we report on a method where platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin (PtTFPP) oxygen indicators are covalently immobilized into a polymer matrix consisting of polystyrene and poly(pentafluorostyrene). We study how the covalent immobilization influences the sensing material's cytotoxicity to human induced pluripotent stem cell-derived (hiPSC-derived) neurons and cardiomyocytes (CMs) through 7-13 days culturing experiments and various viability analyses. Furthermore, we study the effect of the covalent immobilization on the indicator leaching and the oxygen sensing properties of the material. In addition, we demonstrate the use of the covalently linked oxygen sensing material in real time oxygen tension monitoring in functional hypoxia studies of the hiPSC-derived CMs. The results show that the covalently immobilized indicators substantially reduce indicator leaching and the cytotoxicity of the oxygen sensing material, while the influence on the oxygen sensing properties remains small or nonexistent.

Progress on Electrolytes Development in Dye-Sensitized Solar Cells.

Dye-sensitized solar cells (DSSCs) have been intensely researched for more than two decades. Electrolyte formulations are one of the bottlenecks to their successful commercialization, since these result in trade-offs between the photovoltaic performance and long-term performance stability. The corrosive nature of the redox shuttles in the electrolytes is an additional limitation for industrial-scale production of DSSCs, especially with low cost metallic electrodes. Numerous electrolyte formulations have been developed and tested in various DSSC configurations to address the aforementioned challenges. Here, we comprehensively review the progress on the development and application of electrolytes for DSSCs. We particularly focus on the improvements that have been made in different types of electrolytes, which result in enhanced photovoltaic performance and long-term device stability of DSSCs. Several recently introduced electrolyte materials are reviewed, and the role of electrolytes in different DSSC device designs is critically assessed. To sum up, we provide an overview of recent trends in research on electrolytes for DSSCs and highlight the advantages and limitations of recently reported novel electrolyte compositions for producing low-cost and industrially scalable solar cell technology.

The ability of the new ALBI scoring in predicting mortality, complications and prognostic comparison among cirrhotics.

INTRODUCTION: Albumin-bilirubin (ALBI) is a newly devised scoring system for prognostication of liver cirrhosis. The ALBI has recently been validated and found superior to Child-Turcotte-Pugh score (CTP) and Model for End stage Liver Disease (MELD) in assessing severity of liver disease. AIM: To determine the ALBI score's mortality prediction among cirrhotics, associated complications and to compare its prognostic proficiency to that of MELD and CTP. MATERIAL AND METHODS: The diagnostic accuracy of CTP, MELD and ALBI scores for mortality in hospitalized cirrhotic patients was determined by receiver operating characteristic curve (ROC) analysis. The areas under the ROC curve were calculated, with confidence intervals (CI) of 95%. The best cut-off values were ascertained with the greatest specificity and sensitivity. RESULTS: The study showed overall in-hospital mortality of 25.5%. Median CTP score was 10.2 (IQR = 3) and area under curve (AUC) was 0.842 (95% CI: 0.817-0.868, p < 0.001) with sensitivity of 75.0% and specificity of 79.2%. Median MELD score was 20.9 (IQR = 7.2) and AUC was 0.836 (95% CI: 0.810-0.863, p < 0.001) with sensitivity of 76.6% and specificity of 76.7%. Median ALBI score was -1.1 (IQR = 1.0), and AUC of ALBI was 0.852 (95% CI: 0.826-0.879, p < 0.001) with sensitivity and specificity of 78.1%. CONCLUSIONS: The objective prognostication and easy utilization of ALBI make it a useful alternative to MELD and CTP and therefore favour its applicability in clinical practice. Further validations in large prospective cohorts are needed for prognostic value of ALBI in cirrhosis and its complications.

Deal a death blow! HCC in cirrhotics - thrombotic complications: their frequency, characteristics, and risk factors.

INTRODUCTION: The hepatocellular carcinoma (HCC), being the commonest primary cancer, holds the sixth slot in the list of common cancers worldwide. Thrombotic complications in the form of portal vein tumour thrombosis (PVTT) and bland portal vein thrombosis with HCC are common with a bad prognosis. AIM: The study aims to determine the demographic, clinical, and biochemical parameters of HCC patients. The study also compares the clinical and biochemical parameters among patients having HCC with and without thrombotic complication. It further aims to assess the risk factors for thrombotic complication. MATERIAL AND METHODS: This was a retrospective study with a cross sectional design. Clinical and biochemical parameters among patients having HCC with and without thrombotic complication were determined. Tests of statistical significance were applied where a p-value < 0.05 was statistically significant. RESULTS: Overall 118/305 (38.7%) patients of HCC had thrombotic complications. Most of the patients (74.5%) had PVTT whereas in 25.5% bland PVT was found. Higher age, male gender, greater tumour size, advanced stage of HCC (Okuda II, III), multifocal/massive tumour morphology and presence of oesophageal varices, upper GI bleeding, ascites and hepatic encephalopathy, and extrahepatic spread were found to be statistically significant for thrombotic complication (p < 0.05 for each). CONCLUSIONS: Viral related HCC is a commonly reported problem. Thrombotic complication is mainly due to tumour thrombosis rather than bland portal vein thrombosis. Age, gender, greater tumour size, advanced stage of HCC (Okuda II, III), and multifocal/massive tumour morphology were important risk factors for thrombotic complication.

Better prognostic marker in ICU - APACHE II, SOFA or SAP II!

OBJECTIVES: This study was designed to determine the comparative efficacy of different scoring system in assessing the prognosis of critically ill patients. METHODS: This was a retrospective study conducted in medical intensive care unit (MICU) and high dependency unit (HDU) Medical Unit III, Civil Hospital, from April 2012 to August 2012. All patients over age 16 years old who have fulfilled the criteria for MICU admission were included. Predictive mortality of APACHE II, SAP II and SOFA were calculated. Calibration and discrimination were used for validity of each scoring model. RESULTS: A total of 96 patients with equal gender distribution were enrolled. The average APACHE II score in non-survivors (27.97+8.53) was higher than survivors (15.82+8.79) with statistically significant p value (<0.001). The average SOFA score in non-survivors (9.68+4.88) was higher than survivors (5.63+3.63) with statistically significant p value (<0.001). SAP II average score in non-survivors (53.71+19.05) was higher than survivors (30.18+16.24) with statistically significant p value (<0.001). CONCLUSION: All three tested scoring models (APACHE II, SAP II and SOFA) would be accurate enough for a general description of our ICU patients. APACHE II has showed better calibration and discrimination power than SAP II and SOFA.

The heart matters when the liver shatters! Cirrhotic cardiomyopathy: frequency, comparison, and correlation with severity of disease.

INTRODUCTION: Cirrhotic cardiomyopathy is a visor complication among patients with cirrhosis of the liver, manifesting during stress, exertion, transjuglar intrahepatic portosystemic shunt (TIPS), or liver transplantation. Cirrhotic cardiomyopathy is reported to be most common cause of post transplant mortality after rejection of 7% to 21%. AIM: To determine the frequency of cirrhotic cardiomyopathy and was further designed to compare parameters of cardiac dysfunction in patients with or without cirrhotic cardiomyopathy. MATERIAL AND METHODS: All confirmed cases of cirrhosis with various aetiologies were enrolled. Resting ejection fraction (EF) was determined in all patients. Patients were grouped with resting EF < 55% (suspected cardiomyopathy) or > 55% (without cardiomyopathy). Stress echocardiography with dobutamine infusion in both groups yielded an increase of less than 10% in left ventricular (LV) EF at peak dobutamine infusion confirming systolic dysfunction. The diastolic dysfunction (E/A ratio), electrocardiographic parameter (prolong QT interval), and cardiac biomarker (NT-proBNP) were also determined in both the groups to confirm cirrhotic cardiomyopathy. RESULTS: Among 89 patients with cirrhosis, 35 (39.32%) had cirrhotic cardiomyopathy. All components of cirrhotic cardiomyopathy, like systolic dysfunction, diastolic dysfunction, prolong QT interval, and cardiac biomarkers, were found to be statistically significant (p = 0.001) when compared with patients without cardiomyopathy. Cirrhotic cardiomyopathy parameters were positively correlated with advancing liver disease. CONCLUSIONS: Cirrhotic cardiomyopathy is a frequent but unmasked complication in cirrhosis of the liver. All components of cardiac dysfunction, such as systolic, diastolic, and electrocardiographic changes, are present in patients with cirrhotic cardiomyopathy. Cirrhotic cardiomyopathy is positively correlated to severity of liver disease.

Typhidot - A blessing or a menace.

OBJECTIVES: Typhoid remain an increasing problem in Third world countries like Pakistan. A reliable, easy and affordable rapid diagnostic test is a need for our clinicians, many of whom consider Typhidot to be promising. Typhidot has been used as the only tool to diagnose typhoid fever by general practitioners and consultants despite its low sensitivity and specificity causing misdiagnosis and treatment. We therefore conducted this study to evaluate the sensitivity and specificity of Typhidot in patients with fever. METHODS: A retrospective analysis of a total of 145 febrile patients was done. Blood culture and Typhidot along with other relevant investigations had been performed in each case. Sensitivity, specificity and the association of Typhidot to the diagnosis was found using SPSS v16.0. RESULTS: Out of 145 patients, 15(10.3%) had positive blood culture for Salmonella typhi, 7 (4.8%) had positive culture for salmonella paratyphi and 94(64.8%) had positive culture for other organisms. Twenty nine (20%) patients had negative culture results. Forty seven (32.4%) patients had only IgM positive on Typhidot, 7(4.8%) had both IgM and IgG positive and 91(62.8%) had both IgM and IgG negative. Amongst the 130 patients with diseases other than typhoid, 50(38.5%) showed a positive Typhidot result. Amongst the 15 patients with typhoid, 11(73.3%) showed a negative Typhidot result. The sensitivity of Typhidot was found to be 26.7% and the specificity was 61.5%. The Positive Predictive Value (PPV) was 7.4% and the Negative Predictive Value (NPV) was 87.9%. CONCLUSION: Even though Typhidot is rapid, easy and affordable, its use should be discouraged due to low sensitivity and specificity and insignificant (p=0.067) association to the disease.

Inpatient management of type 2 Diabetes Mellitus: Does choice of insulin regimen really matter?

OBJECTIVE: To assess inpatient management of non-critically ill type 2 diabetics with different insulin regimen. METHODS: We reviewed the medical records of all non-critically ill type 2 diabetic patients more than 18 years of age in medical department of civil hospital Karachi and Dow University of Health Sciences from January 2011 to December 2012. We collected the data from case records in data collection sheets that fulfill the inclusion criteria and divided the study subjects into three groups according to insulin regimen they received. RESULTS: A total of 416 patients were analyzed out of which 220 were male. Subjects were divided into three groups according to insulin regimen they received. Majority were put on sliding scale of insulin (44.7%), while 33.1% and 22.1% subjects received basal bolus and pre-mixed insulin regimen respectively. Patients treated with basal bolus regimen had greater improvement in glycaemic control with short duration of hospital stay as compared to other two groups. The mean hyperglycaemic events were higher in sliding scale group while mean hypoglycaemic events were higher in basal bolus group. CONCLUSION: In non-critically ill type 2 diabetic patients the basal bolus regimen is superior to sliding and pre-mixed insulin regimen. Sliding scale should be discouraged in non-critically ill type 2 diabetic patients.

Waldenstroms Macroglobulinemia Patient Presenting with Rare 'lytic' Lesions and Hypercalcemia: A Diagnostic Dilemma.

Waldenstroms macroglobulinemia (WM) is an uncommon B-cell lymphoproliferative neoplasm characterized by lymphoplasmacytic cells infiltrating the Bone Marrow, along with demonstration of an IgM monoclonal gammopathy in the serum. Lytic lesions are considered one of the basis for differentiating a patient of Multiple Myeloma (MM) and WM. However, very few cases have been reported with a patient presenting with lytic lesions in a WM patient, thereby, complicating the disease. By finding the extent of these lytic lesions and bone involvement, Not only can we signify the presence or absence of bone lesions, but we can also direct the more efficient use of skeletal X-rays for documentation of the extent, location, and response of bone abnormalities to interventional chemotherapy and radiation therapy. Our case was mimicking the classic case of MM. Using the International Criteria for diagnosis for WM, diagnosis for MM was excluded and diagnosis for WM was made. After two weeks of therapy, the patient showed marked clinical improvement.

Clinical course, complications and predictors of mortality in patients with tuberculous meningitis--an experience of fifty two cases at Civil Hospital Karachi, Pakistan.

OBJECTIVE: To assess the clinical course, complications and predictors of mortality in reducing the consequent morbidity and mortality in patients with tuberculous meningitis. METHODS: A prospective study was carried out at Civil Hospital Karachi from January 2009 to January 2011. Fifty-two confirmed cases of tuberculous meningitis were included. The entire clinical course with complications and predictors of mortality were assessed. Data was analyzed using SPSS version 17.0. RESULTS: The mean age of the patients was 36.29 +/- 16.7 years with an equal gender distribution. The presenting complaints were fever 51 (98.1%), neck-stiffness 44 (84.61%), and altered level of consciousness 40 (76.9%), headache 31 (59.6%), vomiting 19 (36.5%) and focal weakness 10 (19.2%). Among CNS signs, 47 (90.4%) patients had signs of meningeal irritation, 14 (26.9%) had cranial nerve palsies with abducent nerve being the most commonly involved cranial nerve (25%). Mean GCS was 11.4 +/- 2.9 and most of the patients presented with medical research council Stage 2 of tuberculous meningitis (which is minimally altered level of consciousness with minor focal neurological signs). Overall mortality was 21.1%. Univariate analysis revealed old age; advanced stage of tuberculous meningitis, serum sodium < 125 mmol/l, TLC > 9000/microL development of hydrocephalus and use of mechanical ventilation as major predictors of mortality. CONCLUSION: Tuberculous meningitis is a frequently reported problem in our part of the world. Hydrocephalus along with other sequelae are common complications. All patients should be assessed for the presence of risk factors affecting mortality of the disease.

Determining the frequency and severity of malnutrition and correlating it with the severity of liver cirrhosis.

BACKGROUND/AIMS: Malnutrition is a significant problem in cirrhosis of the liver worldwide. Inadequate data is available on the nutritional status of Pakistani patients. This study aimed to determine the frequency and severity of malnutrition in patients having cirrhosis of the liver and to compare the degree of malnutrition with the severity of liver disease. MATERIALS AND METHODS: Two hundred ninety-eight patients with liver cirrhosis were included in the study. Nutritional status was assessed using the Royal Free Hospital Global Assessment scheme for cirrhotics. The patients were categorized into well-nourished, and mild to moderately and severely malnourished. Various degrees of malnutrition were compared with severity of disease according to Child-Pugh staging. RESULTS: In the 298 patients with liver cirrhosis, hepatitis C (54,36%) and B (35,90%) were the commonest aetiologies, followed by autoimmune hepatitis (3,35%), primary billiary cirrhosis (2,34%), Wilson's disease (1,34%), haemochromatosis (1,0%), cryptogenic cirrhosis (1,0%), and alcohol being the rare cause (0,67%). 14,42% patients were well-nourished, (54,02%) were mildto moderately malnourished and (31,54%) were severely malnourished. Malnutrition is more frequent in virus-related cirrhosis, and the degree of malnutrition increases with increasing clinical severity as assessed by Child- Pugh stages with statistically significant p-value of 0.001. CONCLUSION: Moderate to severe malnutrition among diverse aetiologies of cirrhosis is quite common in Pakistan. The degree of malnutrition increases with increasing clinical severity of cirrhosis of liver.

Clinical profile and management outcome of diabetic foot ulcers in a tertiary care hospital.

OBJECTIVE: To determine major risk factors and management outcome of diabetic foot ulcers in order to prevent amputation. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Study was conducted at the Department of Medicine, Civil Hospital Karachi, from January 2005 to December 2006. PATIENTS AND METHODS: One-hundred and sixteen consecutive diabetic patients, with foot ulcers of Wagner's grade 1 to 4 were assessed at baseline for demographic information, detailed history, neuropathy, peripheral pulses and frequency of diabetic complication. Glycemic control was determined on the basis of HbA1c levels. Appropriate medical and surgical treatments were carried out and patients were followed-up until healing or for 6 months as end point of study. Outcome was recorded as healed, incomplete healing and amputated. RESULTS: A majority of subjects had type 2 diabetes (95.7%) with male predominance (66%). The mean age was 54.29 +/- 7.71 years. Most of the patients were overweight, hyperglycemic and had diabetes > 10 years duration. Neuropathic ulcers were found in 91 (78.4%) patients, while rest of the 25 (22.6 %) had neuroischemic ulcers. Wound cultures revealed polymicrobial organisms. Foot ulcers of 89 (77.7%) patients healed without amputation and 17 (14.7%) patients had minor or major amputations. Long-duration of diabetes, poor glycemic control and type of foot ulcers had effect on prognosis (p<0.05). CONCLUSION: Effective glycemic control, optimal wound care, aggressive medical management and timely surgical intervention may decrease disabling morbidity with better outcome of diabetic foot ulcer.