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1.
J Assoc Physicians India ; 72(4): 68-78, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38881086

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) management is one of the most significant facets of interventional cardiology. Evidence from several clinical trials has redefined the drug management of CAD, including optimizing the duration of antiplatelet treatment regimens in the management of CAD, which is an intricate clinical issue. The available evidence indicates that East Asians have a higher bleeding risk. However, the Indian phenotype differs from that of East Asians, making this data confounding when applied to clinical decision-making among Indian patients. There is a need for a close understanding of Indian interventional cardiologists' perceptions of complex decision-making pertaining to antiplatelet agents among Indian CAD patients in real-world clinical settings. AIM: This Indian Perspective on De-escalation from Dual Antiplatelet Therapy to Single Antiplatelet Therapy (INDEPTH) study aims to assess the perspective of Indian interventional cardiologists regarding de-escalating from dual antiplatelet therapy (DAPT) to single antiplatelet therapy (SAPT), approach to decision-making, barriers, and related challenges in CAD management. METHODS: A cross-sectional knowledge, attitude, and practice (KAP) study survey was carried out among Indian interventional cardiologists practicing across different regions of India. A total of 209 responses were received. Descriptive statistics was used to summarize all the parameters. IBM Statistical Package for the Social Sciences (SPSS) statistics was used for biostatistical analysis. RESULTS: The study indicated that >90% of CAD patients received DAPT therapy immediately after percutaneous coronary intervention (PCI) (86.1%, p < 0.001). About 115 (55%) of the respondents reported using calculator-based scoring for evaluating bleeding risk in patients on DAPT therapy for the management of acute coronary syndrome (ACS) with post-PCI (p = 0.167). Regarding the usual duration of DAPT therapy post-ACS, nearly half of the respondents, 94 (45%), said that 6-12 months is the usual duration for DAPT therapy in post-ACS patients, followed by > 12 months 94 (45%) of the respondents; 17 (8.1%) of the respondents reported it is 3-6 months, and lastly up to 3 months as per four (1.9%) of the respondents (p < 0.001). A total of 128 (61%) of the respondents strongly believe that balancing bleeding with ischemic risk influenced the choice of antiplatelet agent when treating established CAD. As per interventional cardiologists surveyed, the perfect de-escalation time frame for Indian CAD patients with high bleeding risk (HBR) is up to 3 months (35.9%, p < 0.001), 6-12 months for medium bleeding risk (48.8%, p < 0.001), and >12 months for low bleeding risk (65.6%, p < 0.001). Regarding SAPT therapy, almost one-third of the respondents, 65 (31.1%), reported that they prescribed antiplatelet therapy other than aspirin in 20-40% of their SAPT-eligible patients. Furthermore, 69 (33%) of the respondents said that they preferred to prescribe clopidogrel in 50-75% of SAPT-eligible patients. While 64 (30.5%) prescribed in 25-50%, 53 (25.4%) prescribed in <25% and 23 (11%) of the respondents prescribed the drug in >75% of the SAPT-eligible patients. (p < 0.001). "Atorvastatin + clopidogrel" is the most preferred combination of SAPT primarily for the management of CAD among the majority of interventional cardiologists [33%, 95% confidence interval (CI): 1.97-2.24, p < 0.001]. The study respondents also indicated a need for Indian-specific guidelines on de-escalating from DAPT to SAPT in CAD management. CONCLUSION: The INDEPTH study indicated that the majority of CAD patients received DAPT immediately after PCI. The perfect de-escalation time frame for Indian CAD patients with "high-bleeding" risk is up to 3 and 6-12 months for "medium-bleeding" risk and >12 months for "low-bleeding" risk. One-third of respondents used clopidogrel as an antiplatelet agent in 50-75% of SAPT-eligible patients. Atorvastatin + clopidogrel is predominantly the most preferred combination of statin + SAPT for the management of CAD. Although the current international guidelines cover the Indian perspective to some extent, there is a need for Indian-specific guidelines on de-escalating from DAPT to SAPT.


Subject(s)
Cardiologists , Coronary Artery Disease , Dual Anti-Platelet Therapy , Platelet Aggregation Inhibitors , Humans , India , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/therapeutic use , Dual Anti-Platelet Therapy/methods , Coronary Artery Disease/drug therapy , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Practice Patterns, Physicians'/statistics & numerical data , Percutaneous Coronary Intervention/methods , Female , Male , Clinical Decision-Making
2.
J Postgrad Med ; 69(1): 53-55, 2023.
Article in English | MEDLINE | ID: mdl-36453385

ABSTRACT

Sudden bilateral visual loss because of bilateral lateral geniculate body (LGB) necrosis is a very rare entity. The mechanisms causing these isolated lesions have still not been fully understood. We report a case of sudden loss of vision in a 22-year-old female following an attack of acute pancreatitis, just after starting the paleo diet. Neuroimaging revealed bilateral LGB necrosis. Multidisciplinary approach was sought and she was subsequently managed successfully. On follow-up, her visual acuity showed improvement, and neuroimaging revealed resolution of hyperintensities in bilateral LGB with residual blooming suggestive of old hemorrhagic gliosis. The possible reasons for isolated lesions of the LGB are hemorrhagic infarction and osmotic demyelination. In the present case, we postulate a vascular pathology, possibly hypo-perfusion because of shock following acute pancreatitis.


Subject(s)
Geniculate Bodies , Pancreatitis , Humans , Female , Young Adult , Adult , Acute Disease , Geniculate Bodies/blood supply , Geniculate Bodies/pathology , Pancreatitis/complications , Pancreatitis/diagnostic imaging , Vision Disorders/etiology , Vision Disorders/pathology , Blindness , Necrosis/pathology
3.
Public Health ; 219: 131-138, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37167643

ABSTRACT

OBJECTIVES: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign. STUDY DESIGN: This study was a repeated cross-sectional online survey. METHODS: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign. RESULTS: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity. CONCLUSIONS: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese.


Subject(s)
Neoplasms , Overweight , Adult , Humans , Cross-Sectional Studies , Obesity/complications , Obesity/epidemiology , Neoplasms/epidemiology , Neoplasms/etiology , Neoplasms/prevention & control , Health Knowledge, Attitudes, Practice , United Kingdom/epidemiology , Health Promotion
4.
Am J Gastroenterol ; 117(2): 301-310, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34962498

ABSTRACT

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.


Subject(s)
End Stage Liver Disease/etiology , Hepatitis, Alcoholic/mortality , Liver/physiopathology , Adult , Discriminant Analysis , End Stage Liver Disease/mortality , End Stage Liver Disease/physiopathology , Female , Follow-Up Studies , Global Health , Hepatitis, Alcoholic/complications , Hepatitis, Alcoholic/physiopathology , Humans , Liver Function Tests , Male , Middle Aged , Prognosis , ROC Curve , Risk Factors , Severity of Illness Index , Survival Rate/trends , Time Factors
5.
Diabet Med ; 37(12): 2109-2115, 2020 12.
Article in English | MEDLINE | ID: mdl-32353892

ABSTRACT

AIMS: To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. METHODS: This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. RESULTS: The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. CONCLUSIONS: These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Adolescent , Adult , Age of Onset , Blood Glucose Self-Monitoring , Child , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Glycated Hemoglobin/metabolism , Humans , Infusion Pumps, Implantable , Insulin/therapeutic use , Insulin Infusion Systems , Male , Triglycerides/blood , Young Adult
6.
Clin Radiol ; 75(11): 879.e7-879.e11, 2020 11.
Article in English | MEDLINE | ID: mdl-32891409

ABSTRACT

AIM: To assess the discrepancy rates (DR) for patients undergoing abdominopelvic computed tomography (CT) for acute non-traumatic abdominal pain who have a subsequent emergency laparotomy in a large university teaching hospital, in particular identifying the differences between subgroups of reporters, to assess factors that may influence the discrepancy rates, to examine the pathologies with the highest discrepancy rate, to identify learning points, and give recommendations on current practice. MATERIALS AND METHODS: The surgical data and CT reports of 1,176 patients who underwent urgent laparotomy after CT from 2014-2018 in a large university hospital were analysed retrospectively. A major discrepancy was defined as an error of fact in the radiology report, which led to incorrect management or patient harm. RESULTS: Registrars have higher DR than consultants (6.86% versus 2.77%). The major DR for consultants met national standards (<5%). The major DRs for registrars met the national audit standard (<10%), but not the National Emergency Laparotomy Audit (NELA) standard (<5%). When comparing between reporter subgroups, gastrointestinal (GI) radiologists have a lower major DR than general radiologists (1.22% versus 3.44%). GI radiologists were also found to correct more registrar provisional reports. The existence of a documented preoperative discussion between radiologists and surgeons was associated with a lower DR. CONCLUSIONS: DR for registrars and consultants are below the national audit standard. Several factors associated with a lower DR in acute abdominopelvic CT were also identified, including reporting by consultants, reporting by GI radiologists and preoperative discussions between the radiologist and surgeon.


Subject(s)
Abdomen, Acute/diagnostic imaging , Practice Patterns, Physicians'/statistics & numerical data , Tomography, X-Ray Computed/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Laparotomy/statistics & numerical data , Male , Medical Audit , Middle Aged , Radiologists/statistics & numerical data , Retrospective Studies , Surgeons/statistics & numerical data , Young Adult
7.
Geophys Res Lett ; 46(24): 14826-14835, 2019 Dec 28.
Article in English | MEDLINE | ID: mdl-33012881

ABSTRACT

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

8.
Br J Surg ; 105(12): 1591-1597, 2018 11.
Article in English | MEDLINE | ID: mdl-30019751

ABSTRACT

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).


Subject(s)
Aspirin/administration & dosage , Platelet Aggregation Inhibitors/administration & dosage , Vascular Surgical Procedures/adverse effects , Aged , Constriction, Pathologic/etiology , Constriction, Pathologic/mortality , Female , Humans , Male , Myocardial Infarction/etiology , Myocardial Infarction/mortality , Perioperative Care/methods , Perioperative Care/mortality , Platelet Aggregation Inhibitors/adverse effects , Postoperative Complications/chemically induced , Postoperative Complications/prevention & control , Postoperative Hemorrhage/chemically induced , Treatment Outcome , Vascular Diseases/etiology , Vascular Diseases/mortality , Vascular Surgical Procedures/mortality
9.
Osteoporos Int ; 29(3): 733-739, 2018 03.
Article in English | MEDLINE | ID: mdl-29290026

ABSTRACT

We evaluated trabecular bone score (TBS) and factors affecting TBS in adults with type 1 diabetes (T1D) compared to age-, sex-, and body mass index (BMI)-matched adults without diabetes. Adults with T1D had lower TBS compared to controls. Abdominal obesity and insulin resistance are associated with lower TBS. INTRODUCTION: We evaluated TBS, a non-invasive method to evaluate trabecular bone quality at the lumbar spine, in adults with T1D compared to age-, sex-, and BMI-matched adults without diabetes. METHODS: We calculated TBS from adults with T1D (n = 47) and controls (n = 47) who had a lumbar spine dual x-ray absorptiometry (DXA) at their third visit (2006-2009) of the ongoing "Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study." The linear relationships of TBS and bone mineral density (BMD) with hemoglobin A1c, blood pressure, lipids, and insulin resistance were evaluated using Pearson's correlation coefficient. Multiple linear regression was used to test the association of TBS with sex and diabetes while adjusting for other potential confounders. RESULTS: TBS was significantly lower in adults with T1D compared to controls (1.42 ± 0.12 vs 1.44 ± 0.08, p = 0.02) after adjusting for age, sex, current smoking status, and lumbar spine BMD, despite no difference in lumbar spine BMD between the groups. Components of the metabolic syndrome, including diastolic blood pressure, BMI, triglycerides, and insulin resistance were negatively correlated with TBS among patients with T1D. CONCLUSION: Trabecular bone score, an indirect measurement of trabecular bone quality, was lower in adults with T1D compared to controls. Components of metabolic syndrome and insulin resistance were associated with lower TBS in adults with T1D.


Subject(s)
Cancellous Bone/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Insulin Resistance/physiology , Absorptiometry, Photon/methods , Adult , Anthropometry/methods , Bone Density/physiology , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Female , Glycated Hemoglobin/metabolism , Hip Joint/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Male , Middle Aged , Obesity, Abdominal/blood , Obesity, Abdominal/complications , Obesity, Abdominal/physiopathology , Osteoporosis/blood , Osteoporosis/etiology , Osteoporosis/physiopathology
10.
J Eur Acad Dermatol Venereol ; 32(5): 720-734, 2018 May.
Article in English | MEDLINE | ID: mdl-28976026

ABSTRACT

Chemotherapy-induced alopecia (CIA) is a temporary, yet psychologically devastating form of hair loss that affects 65% of patients receiving cancer chemotherapy. In the 1970s, scalp hypothermia was introduced as a preventative measure against the development of CIA. Numerous studies provide evidence for the effectiveness of scalp cooling to prevent CIA, although results varied because of differences in chemotherapy regimen, cooling technique, mode of administration and patient factors. However, many of the existing studies are uncontrolled or consist of small sample sizes, and data from randomized, randomized studies are limited. To date, no clear guidelines have been established for optimum scalp cooling use as a treatment modality and its efficacy remain unknown. Nonetheless, scalp cooling remains the most widely utilized method for the prevention of CIA, and in December 2015, the United States Food and Drug Administration (FDA) cleared the DigniCap® Scalp Cooling System (Dignitana AB, Sweden) for marketing and the Orbis from Paxman® Coolers Ltd. received clearance in 2017. This literature review is one of the first to provide up-to-date review and side-by-side comparisons of controlled and randomized clinical trials (CCTs and RCTs) evaluating scalp hypothermia for the prevention of CIA. Our analyses of CCTs and RCTs to date show that scalp hypothermia is effective in reducing the occurrence rate of CIA, by 2.7-fold in the CCTs and 3.9-fold in the RCTs. These results suggest that scalp hypothermia represents an effective preventative measure for CIA, and provide guidance for management of anticipated alopecia following chemotherapy and for future investigations.


Subject(s)
Alopecia/prevention & control , Antineoplastic Agents/adverse effects , Hypothermia, Induced , Scalp , Alopecia/chemically induced , Humans , Hypothermia, Induced/adverse effects , Hypothermia, Induced/methods , Randomized Controlled Trials as Topic
11.
Indian J Clin Biochem ; 33(4): 479-482, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30319197

ABSTRACT

Hepcidin is a 25-amino acid peptide hormone produced by hepatocytes and plays a key role in body iron metabolism. Hepcidin deficiency is the cause of iron overload in hereditary hemochromatosis, iron-loading anemia, and its excess is associated with anemia of inflammation, chronic disease and iron deficiency anemia (IDA). The aims of this study was to evaluate HAMP gene mutation, namely IVS2 + 1(-G) (c.148-150 + 1del) and Gly71 Asp (c.212G > A (rs104894696) association with iron status in IDA conditions. Our study participants were 500 IDA patients and 550 age and sex-matched healthy controls. Hepcidin, ferritin and CRP analysis was done by ELISA method while ESR analysis was done according to Wintrobe method. CBC analysis was done by auto-analyzer. Two mutations in the HAMP genes were analysed by PCR RFLP method. Among the IDA patients, 7 were heterozygous for Met50del IVS2 + 1(-G) mutation. Nine IDA patients were heterozygous for G71D G-A mutation and homozygous were not identified in both mutations.Controls were showing heterozygous frequency 1.8 and 2.1% of Met50del IVS2 + 1(-G) and G71D G-A mutations respectively. Mutation of HAMP (Met50del IVS2 + 1(-G) and G71D G-A) were clinically associated with IDA and act as modulator of disease.

12.
Neurobiol Dis ; 105: 15-32, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28502806

ABSTRACT

Depression, cognitive impairments, and other neuropsychiatric disturbances are common during the prodromal phase of Huntington's disease (HD) well before the onset of classical motor symptoms of this degenerative disorder. The purpose of this study was to examine the potential impact of physical activity in the form of exercise on a motorized treadmill on non-motor behavioral features including depression-like behavior and cognition in the CAG140 knock-in (KI) mouse model of HD. The CAG140 KI mouse model has a long lifespan compared to other HD rodent models with HD motor deficits emerging after 12months of age and thus provides the opportunity to investigate early life interventions such as exercise on disease progression. Motorized treadmill running was initiated at 4weeks of age (1h per session, 3 times per week) and continued for 6months. Non-motor behaviors were assessed up to 6months of age and included analysis of depression-like behavior (using the tail-suspension and forced-swim tests) and cognition (using the T-maze and object recognition tests). At both 4 and 6months of age, CAG140 KI mice displayed significant depression-like behavior in the forced swim and tail suspension tests and cognitive impairment by deficits in reversal relearning in the T-maze test. These deficits were not evident in mice engaged in treadmill running. In addition, exercise restored striatal dopamine D2 receptor expression and dopamine neurotransmitter levels both reduced in sedentary HD mice. Finally, we examined the pattern of striatal expression of mutant huntingtin (mHTT) protein and showed that the number and intensity of immunohistochemical staining patterns of intranuclear aggregates were significantly reduced with exercise. Altogether these findings begin to address the potential impact of lifestyle and early intervention such as exercise on modifying HD progression.


Subject(s)
Corpus Striatum/pathology , Huntington Disease , Movement Disorders/etiology , Movement Disorders/rehabilitation , Physical Conditioning, Animal , Trinucleotide Repeat Expansion/genetics , Animals , Body Weight/genetics , Depression/etiology , Disease Models, Animal , Dopamine/metabolism , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/rehabilitation , Humans , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntington Disease/complications , Huntington Disease/genetics , Huntington Disease/pathology , Maze Learning , Mice , Mice, Inbred C57BL , Mice, Transgenic , Serotonin/metabolism , Swimming/psychology , Tyrosine 3-Monooxygenase/metabolism
14.
Osteoporos Int ; 28(9): 2601-2610, 2017 09.
Article in English | MEDLINE | ID: mdl-28580510

ABSTRACT

We performed a meta-analysis to evaluate the femoral neck and lumbar spine bone mineral density (BMD) in adults with type 1 diabetes (T1D) compared with controls. Adults with T1D have modestly lower BMD at femoral neck and lumbar spine than adults without diabetes. INTRODUCTION: Fracture risk is four to sixfold higher in adults with T1D. Since BMD is one of the major contributors for fracture risk, we performed a meta-analysis to evaluate differences in femoral neck and lumbar spine BMD between adults with T1D and controls. METHODS: MEDLINE, Ovid, and the Cochrane library and abstracts from various scientific meetings were searched. Studies reporting the femoral neck and/or lumbar spine BMD in adults (age > 20 years) with T1D in comparison with people without diabetes were selected. General linear mixed models were used to assess differences in BMD at femoral neck and lumbar spine between subjects with T1D and controls adjusting for age, sex, and dual x-ray absorptiometry (DXA) instruments. RESULTS: Sixteen studies met the inclusion criteria. The femoral neck BMD was modestly lower in adults with T1D compared to controls (-0.055 g/cm2; 95% CI: -0.065, -0.045). There were no differences in lumbar spine BMD between adults with T1D and controls (0.0062 g/cm2; 95% CI -0.04, 0.016). However, in a sensitivity analysis, lumbar spine BMD was modestly lower in adults with T1D compared to controls (-0.035 g/cm2; -0.049, -0.02). Studies using Lunar DXA instruments have reported higher lumbar spine and femoral neck BMD compared to studies using Hologic DXA instruments. CONCLUSION: Femoral neck and lumbar spine BMD were modestly lower in adults with T1D compared to controls. However, this modest reduction in femoral neck and lumbar spine BMD cannot explain much higher observed fracture risk in adults with T1D.


Subject(s)
Bone Density/physiology , Diabetes Mellitus, Type 1/physiopathology , Femur Neck/physiopathology , Lumbar Vertebrae/physiopathology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Glycated Hemoglobin/metabolism , Humans , Osteoporosis/etiology , Osteoporosis/physiopathology , Osteoporotic Fractures/etiology , Osteoporotic Fractures/physiopathology
15.
Colorectal Dis ; 19(12): 1076-1080, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28696522

ABSTRACT

AIM: Neoadjuvant chemoradiotherapy for locally advanced rectal cancer aims to downstage prior to definitive management. Repeat imaging assessment of the tumour post-therapy has implications for treatment. Our aim was to assess if the inferior mesenteric vein (IMV) diameter measured on CT can be used as a surrogate marker for evaluation of tumour response to neoadjuvant treatment. METHOD: IMV diameter was assessed in patients with and without locally advanced rectal cancer, pre- and post-radiotherapy, to ascertain if IMV diameter is a surrogate marker of tumour response. RESULTS: IMV diameter was 5.9 mm in patients with rectal cancer vs 4.7 mm in patients without (P = 0.0001). The baseline IMV diameter was significantly higher for cases with local lymphadenopathy [N0 5.2 mm vs N1/2 6 mm (P = 0.0059)] and extramural venous invasion (EMVI) [negative 5.4 mm vs positive 6.4 mm (P = 0.0001)]. Post-radiotherapy there was a significant decrease in the IMV diameter in cases with treatment response compared to non-responders: the percentage change in IMV diameter was a 17.54% decrease vs 1.39% increase (P = 0.0001). These results were reproduced on comparing between magnetic resonance tumour regression grades using ANOVA (P = 0.0001). There was also a significant decrease in IMV diameter when assessing lymph node (LN) and EMVI response vs non-responders (P = 0.0001 and 0.0001 respectively). CONCLUSION: Patients with rectal cancer have a dilated IMV compared with patients without rectal cancer. We confirm that IMV diameter is a potential surrogate marker of LN status and EMVI at baseline. IMV diameter is also a marker of tumour, LN and EMVI response to chemoradiotherapy.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/therapy , Chemoradiotherapy, Adjuvant , Magnetic Resonance Angiography/statistics & numerical data , Mesenteric Veins/diagnostic imaging , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Prospective Studies , Rectum/blood supply , Rectum/diagnostic imaging , Retrospective Studies , Treatment Outcome
16.
Am J Transplant ; 16(5): 1559-68, 2016 05.
Article in English | MEDLINE | ID: mdl-26614396

ABSTRACT

Chronic allograft vasculopathy (CAV) limits the lifespan of pediatric heart transplant recipients. We investigated blood markers of inflammation, endothelial dysfunction, and damage to both the native and transplanted vasculature in children after heart transplantation. Serum samples were taken from pediatric heart transplant recipients for markers of inflammation and endothelial activation. The systemic vasculature was investigated using brachial artery flow-mediated dilatation and carotid artery intima-medial hyperplasia. CAV was investigated using intravascular ultrasound. Mean intima-media thickness (mIMT) > 0.5 mm was used to define significant CAV. Forty-eight children (25 male) aged 8-18 years were enrolled in the study. Patients were a median (interquartile range) 4.1 (2.2-8.7) years after transplant. Patients had increased levels of circulating IL6 (3.86 [2.84-4.95] vs. 1.66 [1.22-2.63] p < 0.0001), vascular cell adhesion molecule 1 (539 [451-621] vs. 402 [342-487] p < 0.001), intracellular adhesion molecule 1 305 (247-346) vs. 256 (224-294) p = 0.002 and thrombomodulin (7.1 [5.5-8.1] vs. 3.57 [3.03-4.71] p < 0.0001) and decreased levels of tumor necrosis factor-α, E selectin, and P selectin, compared with controls. The systemic vasculature was unaffected. Patients with severe CAV had raised serum von Willebrand factor and decreased serum thrombomodulin. Posttransplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5 mm. This suggests that subclinical inflammation is present and that natural anticoagulant/thrombomodulin activity is important after transplant.


Subject(s)
Cytokines/metabolism , Endothelium, Vascular/pathology , Heart Transplantation/adverse effects , Inflammation Mediators/metabolism , Inflammation/pathology , Postoperative Complications , Vascular Diseases/pathology , Adolescent , Allografts , Chronic Disease , Endothelium, Vascular/metabolism , Female , Follow-Up Studies , Heart Diseases/complications , Heart Diseases/surgery , Humans , Inflammation/etiology , Inflammation/metabolism , Male , Prognosis , Risk Factors , Vascular Diseases/etiology , Vascular Diseases/metabolism
18.
Am J Transplant ; 15(7): 1915-22, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25809421

ABSTRACT

Laparoscopic kidney transplantation (LKT) is well accepted modality of treatment for ESRD patients at our center. Usually, the kidney is inserted through small Pfannenstiel incision. With the permission of the Internal Review Board, we carried out LKT in eight female recipients following insertion of the kidney through the vagina. The kidney was procured by the retroperitoneoscopic approach. Antibiotic prophylaxis was given. All cases were carried out successfully with immediate graft function and 100% graft and patient survival at 1 year of follow-up. Estimated glomerular filtration rate at 1 month and 1 year was similar to eight randomly selected female recipients who underwent open kidney transplantation (OKT). No analgesia was required in seven out of eight patients after the 3rd postoperative day. In summary, vaginal insertion of kidney and LKT is safe and feasible in a selected group of patients. It is associated with better analgesia and has similar allograft function as compare to OKT.


Subject(s)
Graft Rejection/mortality , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Laparoscopy/methods , Postoperative Complications , Vagina/surgery , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Kidney Function Tests , Male , Middle Aged , Prognosis , Retroperitoneal Space , Risk Factors , Survival Rate
19.
Diabet Med ; 32(9): 1134-42, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26096918

ABSTRACT

AIMS: To conduct a systematic review and meta-analysis of observational studies in order to assess the association between Type 1 diabetes and fractures. BACKGROUND: The risk of fracture in men and women with Type 1 diabetes has not been studied in a large prospective well designed cohort. METHODS: Data were selected from Medline and Embase and abstracts from annual scientific meetings of various diabetes and bone and mineral societies. Published studies that reported the fracture risk in people with Type 1 diabetes in comparison with people without diabetes between 1990 and July 2014 and abstracts from various annual meeting (2005 onwards) were included in the present meta-analysis. Data were extracted from the text of included publications or from abstracts of conferences. RESULTS: The 14 studies that met the inclusion criteria reported 2066 fracture events among 27 300 people with Type 1 diabetes (7.6%) and 136 579 fracture events among 4 364 125 people without diabetes (3.1%). The pooled relative risk of any fracture in people with Type 1 diabetes was 3.16 (95% CI 1.51-6.63; P = 0.002). Women and men with Type 1 diabetes had a four and two times higher risk of any fractures, respectively, compared with people without diabetes. The pooled relative risks of hip fractures and spinal fractures were 3.78 (95% CI 2.05-6.98; P < 0.001) and 2.88 (95% CI 1.71-4.82; P < 0.001), respectively, among people with Type 1 diabetes. CONCLUSIONS: Our meta-analysis suggests that both men and women with Type 1 diabetes might have an increased risk of any fractures. A large prospective epidemiological study is needed to confirm our findings.


Subject(s)
Diabetes Mellitus, Type 1/complications , Osteoporotic Fractures/etiology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Observational Studies as Topic , Risk Factors , Young Adult
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