The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3-11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

In humans, striato-pallido-thalamic projections are largely segregated by their origin in either the striosome-like or matrix-like compartments.

Cortico-striato-thalamo-cortical (CSTC) loops are fundamental organizing units in mammalian brains. CSTCs process limbic, associative, and sensorimotor information in largely separated but interacting networks. CTSC loops pass through paired striatal compartments, striosome (aka patch) and matrix, segregated pools of medium spiny projection neurons with distinct embryologic origins, cortical/subcortical structural connectivity, susceptibility to injury, and roles in behaviors and diseases. Similarly, striatal dopamine modulates activity in striosome and matrix in opposite directions. Routing CSTCs through one compartment may be an anatomical basis for regulating discrete functions. We used differential structural connectivity, identified through probabilistic diffusion tractography, to distinguish the striatal compartments (striosome-like and matrix-like voxels) in living humans. We then mapped compartment-specific projections and quantified structural connectivity between each striatal compartment, the globus pallidus interna (GPi), and 20 thalamic nuclei in 221 healthy adults. We found that striosome-originating and matrix-originating streamlines were segregated within the GPi: striosome-like connectivity was significantly more rostral, ventral, and medial. Striato-pallido-thalamic streamline bundles that were seeded from striosome-like and matrix-like voxels transited spatially distinct portions of the white matter. Matrix-like streamlines were 5.7-fold more likely to reach the GPi, replicating animal tract-tracing studies. Striosome-like connectivity dominated in six thalamic nuclei (anteroventral, central lateral, laterodorsal, lateral posterior, mediodorsal-medial, and medial geniculate). Matrix-like connectivity dominated in seven thalamic nuclei (centromedian, parafascicular, pulvinar-anterior, pulvinar-lateral, ventral lateral-anterior, ventral lateral-posterior, ventral posterolateral). Though we mapped all thalamic nuclei independently, functionally-related nuclei were matched for compartment-level bias. We validated these results with prior thalamostriate tract tracing studies in non-human primates and other species; where reliable data was available, all agreed with our measures of structural connectivity. Matrix-like connectivity was lateralized (left > right hemisphere) in 18 thalamic nuclei, independent of handedness, diffusion protocol, sex, or whether the nucleus was striosome-dominated or matrix-dominated. Compartment-specific biases in striato-pallido-thalamic structural connectivity suggest that routing CSTC loops through striosome-like or matrix-like voxels is a fundamental mechanism for organizing and regulating brain networks. Our MRI-based assessments of striato-thalamic connectivity in humans match and extend the results of prior tract tracing studies in animals. Compartment-level characterization may improve localization of human neuropathologies and improve neurosurgical targeting in the GPi and thalamus.

Prevalence of Type 2 Diabetes Mellitus Among Men in the Middle East: A Retrospective Study.

The rising prevalence of diabetes mellitus (DM) is a serious global health concern. The world is experiencing type 2 diabetes epidemics and prevalence differs by gender, regions, and level of socioeconomic development. Type 2 diabetes mellitus (T2DM) in men increased at a faster rate and numbers are continuing to rise in some regions of the world. This study aimed to estimate the prevalence of T2DM among men in the Middle East countries. Seventy-four research articles were identified through search engines including Web of Science, Medline, PubMed, EMBASE, Scopus, and Ovid databases by using keywords "epidemiology," "prevalence," "diabetes mellitus," and individual names of the Middle East states. Finally, 17 studies were included for the assessment of prevalence of T2DM among men in the Middle East. In the Middle East, high prevalence of T2DM among men was identified in Bahrain (33.60%), Saudi Arabia (29.10%), United Arab Emirates (UAE; 25.83%), and Kuwait (25.40%), whereas low prevalence was reported in Iran (9.90%) and Yemen (9.80%). The random pooled prevalence in the Gulf Cooperation Council (GCC) states was (24.0%) compared to non-GCC states (16.0%), and in both GCC and non-GCC countries combined, it was 19%. The prevalence was significantly associated with the gross domestic product of these states ( p = .0005). Despite different socioeconomic and cultural settings in the Middle East, the rising T2DM prevalence among men was identified in Bahrain, Saudi Arabia, UAE, and Kuwait. These states must incorporate future diabetes defensive strategies targeting the Middle East population to minimize the burden of DM from the region.

Can a diabetic foot be malignant?

Diabetes has been linked with malignancies like colon, rectum, liver, biliary tract, pancreas, kidney, leukaemia and melanoma. Melanoma can sometimes manifest as a diabetic foot ulcer.We describe an elderly male with Type 2 diabetes, who had presented to us with a non-healing wound at the right heel, that later turned out to be an invasive malignant melanoma.

Physiological changes during fasting in Ramadan.

Fasting during Ramadan is one of the five fundamental pillars of Islam and mandatory for all healthy adult Muslims to fast from sunrise to sunset for a period of a month. During fasting, Muslims are required to refrain from all intakes of food, water, beverages, smoking and from sexual intercourse. Ramadan fasting causes many physiological, biochemical, metabolic and spiritual changes in the body. Ramadan Fasting increases the Red Blood Cells (RBCs), White Blood Cells (WBCs), platelet (PLT) count, High Density Lipoprotein Cholesterol (HDL-c), and decreases the blood cholesterol, triglycerides, Low Density Lipoprotein Cholesterol (LDL-c) and Very Low Density Lipoprotein Cholesterol (VLDL-c). Moreover, it reduces body weight, waist circumference, body mass index, body fat, blood glucose, systolic and diastolic blood pressure and anxiety levels. Furthermore, Ramadan fasting decreases the inflammation, pro-inflammatory cytokines IL-1b, IL-6, tumour necrosis factor a and cancer promotion. Among healthy adults, there are no adverse effects of Ramadan fasting on the brain, heart, lung, liver, kidney, haematologic, endocrine profile and cognitive functions. Ramadan fasting is a healthy non pharmacological means for minimizing the risk factors and improving health. Although Ramadan fasting is safe for all healthy individuals, but those with various illnesses such as diabetes mellitus, coronary artery disease, renal and eye illness should consult their physicians and firmly follow the scientific recommendations.

Medical education research in GCC countries.

BACKGROUND: Medical education is an essential domain to produce physicians with high standards of medical knowledge, skills and professionalism in medical practice. This study aimed to investigate the research progress and prospects of GCC countries in medical education during the period 1996-2013. METHODS: In this study, the research papers published in various global scientific journals during the period 1996-2013 were accessed. We recorded the total number of research documents having an affiliation with GCC Countries including Saudi Arabia, Bahrain, Kuwait, Qatar, United Arab Emirates and Oman. The main source for information was Institute of Scientific Information (ISI) Web of Science, Thomson Reuters. RESULTS: In ISI-Web of Science, Saudi Arabia contributed 40797 research papers, Kuwait 1666, United Arab Emirates 3045, Qatar 4265, Bahrain 1666 and Oman 4848 research papers. However, in Medical Education only Saudi Arabia contributed 323 (0.79%) research papers, Kuwait 52 (0.03%), United Arab Emirates 41(0.01%), Qatar 37(0.008%), Bahrain 28 (0.06%) and Oman 22 (0.45%) research papers in in ISI indexed journals. In medical education the Hirsch index (h-index) of Saudi Arabia is 14, United Arab Emirates 14, Kuwait 11, Qatar 8, Bahrain 8 and Oman 5. CONCLUSION: GCC countries produced very little research in medical education during the period 1996-2013. They must improve their research outcomes in medical education to produce better physicians to enhance the standards in medical practice in the region.

A cross-sectional assessment of health-related quality of life among type 2 diabetes patients in Riyadh, Saudi Arabia.

OBJECTIVE: This study aimed to describe the health-related quality of life profile among type 2 diabetes patients in Riyadh, Saudi Arabia. METHOD: A cross-sectional study was undertaken using a cohort of 75 patients attending the University Diabetic Centre at King Abdulaziz University Hospital, Riyadh, Saudi Arabia. EuroQoL-5 dimension (EQ-5D) scale was used for the assessment of health-related quality of life. EQ-5D was scored using values derived from the UK general population survey. Inferential statistics were applied to evaluate associations between study variables. The Statistical Package for Social Sciences version 20.0 was used for data analysis; p <0.05 was set as the level of statistical significance. RESULTS: Fifty-eight (77.35%) respondents were male with a mean 12.6 ± 8.4 years of history of diabetes. Thirty-four (45.3%) were categorised into the age group of 45-55 years with a mean age of 54 ± 9.2 years. Forty-four (58.7%) were using oral hypoglycaemic agents and 40 (53.3%) had a university level of education. A moderate level of health-related quality of life (0.70 ± 0.22) was measured in the study cohort. Gender was significantly associated with health-related quality of life scores (p = 0.001). The mean EQ-5D score was lower in females compared to male patients (0.58 ± 0.23 vs 0.74 ± 0.20). There were no statistically significant associations between health-related quality of life scores and age groups, duration of diabetes, marital status, educational level and type of treatment. CONCLUSION: This study has highlighted that Saudi diabetes patients have low levels of health-related quality of life. Healthcare professionals need to consider this when planning holistic patient treatment approaches.

Prevalence of urinary tract infection and risk factors among Saudi patients with diabetes.

PURPOSE: The aim of this study is to assess the prevalence of urinary tract infection (UTI) and its risk factors among Saudi diabetics. METHOD: A total of 1,000 diabetic patients were included. Patients were interviewed and examined at each visit every 6 months. RESULTS: The prevalence of UTI was 25.3 % in total diabetic population and 7.2 and 41.1 % in males and females, respectively. Females have highest risk of UTI (RR = 6.102; CI = 4.343-8.573; P < 0.001). Age, duration of diabetes and HbA1c did not influence the incidence of UTI, while BMI above 30 kg/m(2) increased the risk (RR = 1.722; CI = 1.532-1.935; P < 0.001). The incidence of UTI in both type 1 and 2 diabetics was similar (23.7 and 25.6 %). There was no significant risk in patients aged above 60 years (RR = 1.054; CI = 0.841-1.321; P = 0.651). The risk factors found to be associated with UTI were hypertension (RR = 1.202; CI = 1.061-1.361; P = 0.006), insulin therapy (RR = 1.411; CI = 1.262-1.578; P < 0.001) and nephropathy (microalbuminuria) (RR = 1.417; CI = 1.036-1.939; P = 0.031). CONCLUSION: The present study has shown that prevalence of UTI is more in diabetic females and diabetics with BMI above 30 kg/m(2). The other risk factors associated with UTI in general diabetic population were found to be microalbuminuria, hypertension and insulin therapy.

Frequency of the metabolic syndrome in type 2 diabetic subjects attending the diabetes clinic of a tertiary care hospital.

OBJECTIVE: To determine the frequency of the metabolic syndrome in patients with type 2 diabetes mellitus wiho attended the diabetes clinic of Liaquat National Hospital, Karachi. METHOD: A descriptive study was conducted at the diabetes clinic of Liaquat National Hospital from June 2004 to December 2004. We enrolled 233 subjects with type 2 diabetes mellitus. Frequency of metabolic syndrome was estimated according to the criteria proposed by National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), with adoption of the Asian criteria for abdominal obesity and recently proposed International Diabetes Federation (IDF) diagnostic criteria for metabolic syndrome. RESULTS: There were 233 patients with type 2 diabetes mellitus in whom 49.8% were men and 50.2% were women. Mean age was 49.9 years. By applying NCEP-ATP III criteria, metabolic syndrome was found in 79.7% type 2 diabetics, (45.5% women and 34.3% men), by applying IDF criteria, metabolic syndrome was identified in 68.1% of type 2 diabetics (43.7% women and 24.4% men). CONCLUSION: In our study the frequency of the metabolic syndrome was found significantly high, especially in women and at a relatively young age of 49.9 years.

An adult with Morquio syndrome.

We report a case of a 25-year-old male who came to endocrine clinic to get medical certificate so as to claim as the shortest man of the world. He was evaluated for short stature and eventually diagnosed with type-IV mucopolysaccharidosis (MPS) or Morquio syndrome.