Temporal Changes in Intraluminal Thrombus Volume Within Abdominal Aortic Aneurysms: Implications for Planning Endovascular Aneurysm Sealing.

PURPOSE: To explore whether or not there are temporal changes in the abdominal aortic aneurysm (AAA) and intraluminal thrombus (ILT) volumes between planning and implantation of the endovascular aneurysm sealing (EVAS) device and how these changes influence lumen volume. METHODS: A retrospective review was conducted of 51 AAA patients (mean age 76±7.1 years; 36 men) in whom 2 serial preoperative computed tomography angiograms (CTAs) had been performed within 1 to 18 months before fenestrated endovascular repair. The 2 preoperative CTAs were analyzed to identify changes in total sac, ILT, and lumen volumes. RESULTS: Over a median 7.0 months (interquartile range 4, 10), 46 (90%) of 51 AAAs increased in volume between the 2 CTAs. ILT volume increased in 44 aneurysms. In contrast, lumen volume increased in 31 and decreased in 20 AAAs. There was a strong correlation between changes in AAA volume and ILT volume (rs=0.859, p<0.001), which remained significant after adjustment for initial volumes (rs=0.815; p<0.001). There was no correlation between the time interval separating the 2 CTAs and changes in AAA volume (rs=0.115; p=0.421), changes in ILT volume (rs=0.084; p=0.599), or changes in lumen volume (rs=0.060; p=0.676). The AAA growth rate (defined as the change in AAA size/days between CTAs) showed a weak correlation with ILT volume (rs=0.272, p=0.054), which disappeared after adjustment for initial AAA size (rs=-0.002, p=0.991). Between the 2 CTAs, 12 aneurysms crossed the new <1.4 Nellix maximum aorta/lumen diameter ratio. CONCLUSION: As AAAs grow, the increase in aortic volume is largely occupied by additional ILT formation, with minimal change in lumen volume. These changes may alter the suitability of the aneurysm for the Nellix device and could have implications for EVAS planning and device deployment.

Comparison of Measurement and Grading of Carotid Stenosis with Computed Tomography Angiography and Doppler Ultrasound.

BACKGROUND: Doppler ultrasound (DUS) and computed tomography angiography (CTA) are the most commonly used imaging modalities for carotid disease. The aim of this study was to test the accuracy and reproducibility of CTA-derived measurements of carotid stenosis and compare them with those obtained by DUS. METHODS: Images of 100 carotid arteries of patients who underwent carotid DUS at our unit and CTA of the carotids within a 28-day period were identified retrospectively from multidisciplinary team meeting records. CTAs were assessed by 2 investigators, each using a manual and a semi-automated method. With both methods, the degree of stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial equation and graded as mild (0-49%), moderate (50-69%), or severe (70-99%). Cohen's kappa and specificity and sensitivity for ≥50% stenosis were calculated. RESULTS: The interobserver agreement was moderate (κ 0.407, weighted-κ 0.517) for the manual method and good (κ 0.786, weighted-κ 0.842) for the semi-automated method. Using DUS as the gold standard, the semi-automated method had greater sensitivity (75%) and specificity (91%) in detecting clinically significant carotid artery stenosis (≥50%) than the manual one (63% and 86%, respectively). Agreement between DUS and the semi-automated method of CTA reporting was moderate (κ 0.453, 95% confidence interval [CI]: 0.320-0.586, weighted-κ 0.598, 95% CI: 0.486-0.710), whereas DUS and the manual method of CTA reporting had only fair agreement (κ 0.344, 95% CI: 0.209-0.478, weighted-κ 0.446, 95% CI: 0.315-0.577). CONCLUSIONS: CTA tends to underestimate the degree of stenosis when compared with DUS. The semi-automated method of CTA reporting has greater reproducibility and greater agreement with DUS. These findings have practical implications when CTA is used to measure the degree of carotid stenosis in clinical practice.

Renal Stent Crushed During Open Aneurysmorrhaphy for Endoleak After Fenestrated EVAR.

PURPOSE: To report a complication of renal stent crushing during open aneurysmorrhaphy performed 10 years after fenestrated endovascular aneurysm repair (FEVAR). CASE REPORT: A 67-year-old male patient underwent elective FEVAR of a juxtarenal aortic aneurysm. Uncovered balloon-expandable stents were placed through the fenestrations for the superior mesenteric and right renal arteries; the left renal artery received a Jostent covered balloon-expandable stent. The uncovered right renal stent was noted to be crushed on the first imaging after FEVAR, but was left untreated; the right kidney was thereafter significantly smaller than the left. Over several years, the aneurysm expanded, and type II endoleak involving the lumbar arteries was embolized with coils 7 years after FEVAR. Despite this, the aneurysm continued to enlarge and reached a diameter of 12.8 cm. Open aneurysmorrhaphy and selective ligation of lumbar arteries was performed 10 years after FEVAR. The first surveillance imaging after aneurysmorrhaphy demonstrated a new finding of a crushed left renal stent, which was presumed to be related to surgical instrumentation. The stent was successfully redilated percutaneously, and renal function remained stable. Computed tomography demonstrated a normal appearance of the left renal covered stent after re-expansion. Doppler ultrasound after 7.5 months showed normal renal perfusion. CONCLUSION: Balloon-expandable visceral artery stents are susceptible to crush injury during aortic surgery. Consideration should be given to early imaging after such surgery in FEVAR patients.

Changes in Aortic Volumes Following Endovascular Sealing of Abdominal Aortic Aneurysms With the Nellix Endoprosthesis.

PURPOSE: To investigate the effects on aortic volumes of endovascular aneurysm sealing (EVAS) with the Nellix device. METHODS: Twenty-five consecutive patients (mean age 78±7 years; 17 men) with abdominal aortic aneurysms containing thrombus were treated with EVAS. Their pre- and post-EVAS computed tomography (CT) scans were reviewed to document volume changes in the entire aneurysmal aorta, the lumen, and the intraluminal thrombus. The changes are reported as the mean and 95% confidence interval (CI). RESULTS: Total aortic volume was greater on postoperative scans by a mean 17 mL (95% CI 10.0 to 23.5, p<0.001). The volume occupied by the endobags was greater than the preoperative lumen volume by a mean 28 mL (95% CI 24.7 to 31.7, p=0.002). Postoperatively, the aortic volume occupied by thrombus had decreased by a mean 11 mL (95% CI 4.7 to 18.2, p<0.001). There were good correlations between changes in aneurysm and thrombus volumes (r=0.864, p<0.001), between the planning CT/EVAS time interval and the change in aneurysm volume (r=0.640, p=0.001), and between the planning CT/EVAS time interval and the change in thrombus volume (r=0.567, p=0.003). CONCLUSION: There are significant changes in aortic volumes post EVAS. These changes may be a direct consequence of the technique and have implications for the planning and performance of EVAS.

Estimating window period blood donations for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus by nucleic acid amplification testing in Southern Pakistan.

BACKGROUND: Recently, strategic planning was initiated by the National Blood Transfusion Services Pakistan to improve its blood bank facilities. Emphasis has been placed on appropriate screening of blood products. Located in the southern region, Aga Khan University Hospital is a 700-bed tertiary care academic institute with comprehensive blood banking. Screening of blood donors has been based on verbal screening and serologic testing to date. Additionally, the need of implementing nucleic acid testing (NAT) was considered in 2011 because of an upsurge in hepatitis epidemiology. The aim of this study was to analyze the efficacy of this additional donor screening program and to evaluate the impact of NAT on the yield and residual risk of transfusion-transmissible viral infections. STUDY DESIGN AND METHODS: A total of 42,830 blood donations collected between 2011 and 2012 were screened for routine serologic assays. Only serologically negative donors (n=41,304) were tested for NAT. The frequency of viral infections was evaluated through serologic techniques and NAT yield for viral agents was estimated for computing window period donors. Residual risk per million donors was computed for viral infections in seronegative blood donors. RESULTS: Serologic work-up showed 1571 abnormal screening results in 1526 blood donors with the following results: hepatitis C virus antibodies (anti-HCV; n=708), hepatitis B surface antigen (n=555), human immunodeficiency virus antibodies (anti-HIV; n=29), malaria (n=30), VDRL (n=249), and coinfection (n=45). Thirty-five NAT-reactive samples were identified: HIV-1, one; HCV, 27; and hepatitis B virus (HBV), seven. Incident rates per 10(5) donors were highest for HCV (453.3) followed by HBV (171.5) and HIV (72.2). Calculated residual risk per million donors was highest at 1 in 10,900 for HBV, intermediate at 1 in 13,900 for HCV, and least at 1 in 62,600 for HIV. CONCLUSION: Incidence rates and estimated residual risk indicate that the current risk of transfusion-transmitted viral infections attributable to blood donation is relatively high in this country. The study recommends the parallel use of both serology and NAT screening of donated blood in countries that have high seroprevalence of these viral infections.

Real-World Outcomes in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma Treated With Bortezomib/Cyclophosphamide/Dexamethasone and Bortezomib/Lenalidomide/Dexamethasone as Upfront Treatment.

Introduction Multiple myeloma (MM) is a hematological disorder characterized by aberrant multiplication of malignant plasma cells in the bone marrow. The current mainstay of treatment for patients with newly diagnosed MM (NDMM) is a triplet regimen with a proteasome inhibitor, immunomodulatory imide, and dexamethasone. The two most common of these triplet regimens are VLD (bortezomib/lenalidomide/dexamethasone) and VCD (bortezomib/cyclophosphamide/dexamethasone). This study aims to compare the outcomes between these two therapies in transplant-ineligible patients with NDMM. Methods We conducted a retrospective study at the Aga Khan University Hospital in Karachi, Pakistan. All NDMM transplant-ineligible patients either receiving VLD or VCD therapy between January 2015 and December 2022 were included in our study. Hematological parameters before and after treatment were obtained from hospital records. Response to treatment was classified according to the International Myeloma Working Group (IMWG) response criteria as either complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), or progressive disease (PD). The response to treatment as well as overall survival (OS) and progression-free survival (PFS) was compared between VCD and VLD therapy. A p-value of 0.05 or less was taken to be statistically significant. Results Twenty (23.8%) patients in the VCD group and 20 (23.0%) in the VLD group underwent complete remission. Seven (8.3%) patients experienced disease progression in the VCD group, while the figure stood at three (3.4%) in the VLD group. There was no statistically significant difference in the overall response rate between the VCD (58; 69.0%) and VLD (70; 80.5%) groups (p=0.086), a difference that was not statistically significant on the Chi-square test. OS was comparable between VCD (69.1 months, 95%CI: 61.3-77.0) and VLD (76.9 months, 95%CI: 69.0-85.0) therapies. Conclusions The study did not identify any statistically significant distinction in the treatment outcomes between the VCD and VLD regimens among NDMM patients ineligible for transplantation. Nevertheless, the study highlights the positive outcomes observed with both treatments in this specific patient cohort. This implies that either regimen could be deemed suitable as a treatment option for patients in low- and middle-income countries. Since both regimens demonstrate comparable effectiveness, assessing the cost-effectiveness of these regimens is crucial. Future research should also explore the economic aspects of the two treatment options.

Clinical Outcome of Patients Receiving Rituximab in Combination with Bendamustine in Indolent B-cell Lymphomas: A Single-center Institutional Study.

Introduction: Indolent non-Hodgkin's lymphomas (NHLs) are a diverse category of malignancies characterized by a chronic relapsing-remitting disease course. In the modern era, patients usually receive a combination of bendamustine plus rituximab as the initial therapy, otherwise known as an R-Benda regimen. While clinical trials have demonstrated R-Benda to be superior to other regimens, our study aims to provide insight into real-world outcomes of R-Benda therapy. Materials and Methods: We conducted a retrospective study for January 2015-July 2022 among patients receiving R-Benda for indolent NHLs at the Aga Khan University Hospital, Karachi, Pakistan. All patients underwent pre- and post-treatment assessment through positron emission tomography scan and computed tomography (CT) imaging. The response to treatment was assessed, and the overall survival (OS) and progression-free survival (PFS) were assessed using a Kaplan-Meier survival analysis. Results: We enrolled 118 patients, out of which the majority were elderly males (64%). The 2-year follow-up rate was 76.3% (n = 90), and the median follow-up time was 29 months. The most common histopathology encountered was follicular lymphoma (52%) presenting with stage IV disease (56%). Approximately 73% experienced a complete metabolic response to the treatment. Of these, 31.4% subsequently experienced a relapse. In addition, 17.7% of patients underwent a partial response, while 7% had refractory disease. The mean OS was 140 months (95% CI: 120-160), while the lower quartile value was 50 months. On the other hand, the median PFS was 80 months (95% CI: 43-N/A). Conclusion: Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had no disease progression for the first 2 years. It adds to the existing body of literature that demonstrates that in real-world experience, the outcomes of R-Benda treatment are better than those reported by earlier randomized-control trials.

Does repetitive transcranial magnetic stimulation have a beneficial effect on improving unilateral spatial neglect caused by stroke? A meta-analysis.

This review aimed to assess the effect of repetitive transcranial magnetic stimulation (rTMS) in improving post-stroke unilateral spatial neglect (USN) using a meta-analysis. Further, we aimed to identify any association between rTMS parameters, patient demographics, and treatment effect sizes using subgroup analyses and meta-regression. A literature search was conducted through four databases from inception to March 6, 2024, to retrieve all relevant controlled trials investigating the effects of rTMS on symptoms of USN in post-stroke patients. Overall, rTMS significantly improved post-stroke USN, as measured by the line bisection test (Hedges' g = - 1.301, p < 0.0001), the cancelation test (Hedge's g = - 1.512, p < 0.0001), and the Catherine Bergego Scale (Hedges'g = - 0.770, p < 0.0001), compared to sham stimulation. Subgroup analysis found that generally larger effect sizes following excitatory rTMS across several outcome measures, indicating that excitatory rTMS on the ipsilesional hemisphere may be more effective than inhibitory rTMS on the contralesional hemisphere in ameliorating neglect symptoms. Meta-regression analysis of the line bisection test showed a significant difference in the chronicity of stroke patients, suggesting that rTMS may be more effective for USN in patients at the acute stage (within 3 months since stroke) than in those at the post-acute stage (p = 0.035). In conclusion, rTMS appears to be effective in promoting recovery from post-stroke USN. Excitatory protocols and early intervention may enhance recovery outcomes for neglect behaviors in post-stroke survivors.

Robust and adaptive terrain classification and gait event detection system.

Real-time gait event detection (GED) system can be utilized for gait analysis and tracking fitness activities. GED for various types of terrains (e.g., stair-walk, uneven surfaces, etc.) is still an open research problem. This study presents an inertial sensor-based approach for real-time GED system that works for diverse terrains in an uncontrolled environment. The GED system classifies three types of terrains, i.e., flat-walk, stair-ascend and stair-descend, with an average classification accuracy of 99%. It also accurately detects various gait events, including, toe-strike, heel-rise, toe-off, and heel-strike. It is computationally efficient, implemented on a low-cost microcontroller, works in real-time and can be used in portable rehabilitation devices for use in dynamic environments.

Outcomes of Patients with FLT3 Positive Acute Myeloid Leukaemia; an Experience from a Tertiary Care Hospital in Karachi, Pakistan.

Introduction: Molecular genetic abnormalities in acute myeloid leukaemia (AML) are essential for disease diagnosis and determining prognosis and clinical course. Mutations in FLT3 and nucleophosmin (NPM) genes are the most frequent genetic abnormalities, which are also known to impact disease outcomes. FLT3 mutations have been identified in approximately 30% of de novo AML patients and are associated with poor prognoses. This study aimed to determine the response to induction chemotherapy, overall survival (OS) and relapse rate (RR) in patients with FLT3-positive AML. Materials and Methods: In this study, a retrospective analysis was performed of 75 newly diagnosed patients with AML registered between January 2015 and July 2022. Patient demographics and clinical-haematological parameters were noted and molecular analysis for FLT3 ITD/TKD and NPM mutations was performed. All the patients received standard induction chemotherapy and their response to treatment, OS and RR were assessed. Results: A total of 75 cases of AML were analysed. The mean age of the sample was 34.9 years, of which 65.3% were males and 34.7% were females. The patients were stratified into two groups: Those who were positive for FLT3 while negative for NPM (FLT3+/NPM-), representing 17.3% and those who were negative for both FLT3 and NPM (FLT3-/NPM-), representing 82.7% of cases. On day 28 post-induction, the complete remission rate was 69.2% in the FLT3 positive group and 77.4% in the FLT3 negative group. In the FLT3+/NPM- group, 55.6% of cases who were in remission at day 28 subsequently relapsed, compared to 50.0% of FLT3-/NPM- cases. The overall median survival time for the cohort and FLT3+ group was 1467 days, while that of the FLT3-group could not be estimated due to the very high survival rate. Conclusion: No significant differences in outcomes were observed in patients who were FLT3 positive compared to those who were FLT3 negative.

Increasing striatal dopamine release through repeated bouts of theta burst transcranial magnetic stimulation of the left dorsolateral prefrontal cortex. A 18F-desmethoxyfallypride positron emission tomography study.

Introduction: Transcranial Magnetic Stimulation (TMS) can modulate fronto-striatal connectivity in the human brain. Here Positron Emission Tomography (PET) and neuro-navigated TMS were combined to investigate the dynamics of the fronto-striatal connectivity in the human brain. Employing 18F-DesmethoxyFallypride (DMFP) - a Dopamine receptor-antagonist - the release of endogenous dopamine in the striatum in response to time-spaced repeated bouts of excitatory, intermittent theta burst stimulation (iTBS) of the Left-Dorsolateral Prefrontal Cortex (L-DLPFC) was measured. Methods: 23 healthy participants underwent two PET sessions, each one with four blocks of iTBS separated by 30 minutes: sham (control) and verum (90% of individual resting motor threshold). Receptor Binding Ratios were collected for sham and verum sessions across 37 time frames (about 130 minutes) in striatal sub-regions (Caudate nucleus and Putamen). Results: Verum iTBS increased the dopamine release in striatal sub-regions, relative to sham iTBS. Dopamine levels in the verum session increased progressively across the time frames until frame number 28 (approximately 85 minutes after the start of the session and after three iTBS bouts) and then essentially remained unchanged until the end of the session. Conclusion: Results suggest that the short-timed iTBS protocol performed in time-spaced blocks can effectively induce a dynamic dose dependent increase in dopaminergic fronto-striatal connectivity. This scheme could provide an alternative to unpleasant and distressing, long stimulation protocols in experimental and therapeutic settings. Specifically, it was demonstrated that three repeated bouts of iTBS, spaced by short intervals, achieve larger effects than one single stimulation. This finding has implications for the planning of therapeutic interventions, for example, treatment of major depression.

Biomimetic Approaches in Cardiac Tissue Engineering: Replicating the Native Heart Microenvironment.

Cardiovascular diseases, including heart failure, pose significant challenges in medical practice, necessitating innovative approaches for cardiac repair and regeneration. Cardiac tissue engineering has emerged as a promising solution, aiming to develop functional and physiologically relevant cardiac tissue constructs. Replicating the native heart microenvironment, with its complex and dynamic milieu necessary for cardiac tissue growth and function, is crucial in tissue engineering. Biomimetic strategies that closely mimic the natural heart microenvironment have gained significant interest due to their potential to enhance synthetic cardiac tissue functionality and therapeutic applicability. Biomimetic approaches focus on mimicking biochemical cues, mechanical stimuli, coordinated electrical signaling, and cell-cell/cell-matrix interactions of cardiac tissue. By combining bioactive ligands, controlled delivery systems, appropriate biomaterial characteristics, electrical signals, and strategies to enhance cell interactions, biomimetic approaches provide a more physiologically relevant environment for tissue growth. The replication of the native cardiac microenvironment enables precise regulation of cellular responses, tissue remodeling, and the development of functional cardiac tissue constructs. Challenges and future directions include refining complex biochemical signaling networks, paracrine signaling, synchronized electrical networks, and cell-cell/cell-matrix interactions. Advancements in biomimetic approaches hold great promise for cardiovascular regenerative medicine, offering potential therapeutic strategies and revolutionizing cardiac disease modeling. These approaches contribute to the development of more effective treatments, personalized medicine, and improved patient outcomes. Ongoing research and innovation in biomimetic approaches have the potential to revolutionize regenerative medicine and cardiac disease modeling by replicating the native heart microenvironment, advancing functional cardiac tissue engineering, and improving patient outcomes.

Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions.

Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating mutations of the ACVR1 gene. FOP affects both the developmental and postnatal stages, resulting in musculoskeletal abnormalities and heterotopic ossification. Current treatment options for FOP are limited, emphasizing the need for innovative therapeutic approaches. Challenges in the development of management criteria for FOP include difficulties in recruitment due to the rarity of FOP, disease variability, the absence of reliable biomarkers, and ethical considerations regarding placebo-controlled trials. This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment. Gene therapy, particularly the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system, holds promise in treating FOP by specifically targeting the ACVR1 gene mutation. Another gene therapy approach being investigated is RNA interference, which aims to silence the mutant ACVR1 gene. Small molecule inhibitors targeting glycogen synthase kinase-3ß and modulation of the bone morphogenetic protein signaling pathway are also being explored as potential therapies for FOP. Stem cell-based approaches, such as mesenchymal stem cells and induced pluripotent stem cells, show potential in tissue regeneration and inhibiting abnormal bone formation in FOP. Immunotherapy and nanoparticle delivery systems provide alternative avenues for FOP treatment.

Double Mesh Nitinol Stent Versus Self-expanding Stent-graft in Recurrent/Resistant Cephalic Vein Arch Stenoses in Dialysis Fistulae: A Comparative Study.

PURPOSE: To compare the double mesh nitinol stent (DNS) versus the self-expanding stent-graft (SES) in recurrent/resistant cephalic vein arch stenosis in dialysis fistulae. MATERIALS AND METHODS: 17 cases with recurrent/resistant stenosis of the cephalic vein arch treated with a DNS were compared retrospectively with 18 cases treated with an SES. Stenting was performed either for significant recoil post-angioplasty with high-pressure balloons or in recurrent stenoses. Patients were followed up with Doppler ultrasound in our vascular access surveillance programme. Primary and assisted primary patency rates at 3, 6 and 12 months were estimated by Kaplan-Meier analysis. RESULTS: Both stents showed 100% technical success immediately post-stenting, defined as residual stenosis < 30%. 3, 6 and 12 month primary patency of the DNS was 82.4%, 69.7% and 28.1% versus 88.9%, 77.8% and 72.2% for the SES. The DNS had a mean primary patency of 242.4 days compared to 896.3 days for the SES (p = 0.021). 12 month assisted primary patency was 88.2% (DNS) and 100% (SES). The DNS had a mean assisted primary patency of 812 days compared to 1390.3 days for the SES, though this did not reach statistical significance. No stent fractures were identified at 2 years in either group. CONCLUSION: Both stents had 100% technical success with no stent fractures. SES showed statistically significant higher primary patency. Assisted primary patency was also higher, though this did not reach statistical significance.

Comparison of Testosterone Levels in Patients With and Without Type 2 Diabetes.

Introduction Hypogonadotropic hypogonadism is a common disorder associated with type 2 diabetes. Hypogonadotropic hypogonadism in type 2 diabetic patients requires further assessment to understand the etiology, and the possible consequences, complications, and treatment This study aims to highlight the testosterone level in type 2 diabetes mellitus (DM). Moreover, it further emphasizes the association of testosterone with the duration of DM. Materials and method This case-control survey was conducted from September 2020 to March 2021 in the outpatient department of internal medicine in a tertiary care hospital in Pakistan. The experiment group included 200 diabetic male participants aged between 30 and 69 years. In the control group, 200 participants without DM were enrolled in the study. The venous blood sample was collected via phlebotomy and sent to the laboratory to test for total testosterone level. Results The mean total testosterone level was significantly lower in diabetic patients compared to the non-diabetic patients (8.9 ± 5.1 mmol/L vs. 14.1 ± 7.2 mmol/L; p-value: <0.0001) and the prevalence of androgen deficiency was significantly higher in diabetic patients compared to non-diabetic patients (45.5% vs. 20.5%; p-value: <0.00001). For each age group, the mean total testosterone level was significantly higher in the diabetic group compared to the non-diabetic group. There was a significant decline in mean total testosterone level as the duration of diabetes increased (p-value: 0.01). Conclusion Strong interlink between type 2 DM and low testosterone level has once again highlighted the importance of a broader approach toward men presenting in the diabetic clinic and provided a huge ground for prescribing testosterone replacement therapy in hypogonadal men with DM.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

LMP1 expression in bone marrow trephines of patients with multiple myeloma confers a survival advantage.

Multiple myeloma (MM) is a heterogeneous disease of the bone marrow (BM). Its association with Epstein-Barr virus (EBV) remains enigmatic. Aim of our study was to determine expression of latent membrane protein 1 (LMP1), aldehyde dehydrogenase 1 (ALDH1), CD117 and their association with 5-year survival in MM patients. Seven percent of cases expressed LMP1 in MM cells with no association with survival. Whereas, LMP1 expression in CD138- non-neoplastic cells was observed in 80% of the cases, conferring a survival advantage of 1.75 years (mean 3.75 ± 0.28, 95% CI 3.19-4.3). LMP1 in CD138- non-neoplastic cells was associated with CD117 expression in MM cells. Combinatorial analysis of LMP1 and CD117 stratified patients into good prognostic group LMP1+/CD117- (mean survival 4.16 ± 0.39 years) and a worst prognostic group; LMP1-/CD117+ (mean survival 1.02 ± 0.29 years). Our study showed that LMP1 expression in CD138- non-neoplastic cells of BM in MM patients confers a survival advantage.

Diagnostic tool for Glanzmann's thrombasthenia clinicopathologic spectrum.

OBJECTIVE: To platelet aggregometry and describe the clinical spectrum of Glanzmann's thrombasthenia diagnosed by platelet aggregometry. STUDY DESIGN: A case-series. PLACE AND DURATION OF STUDY: This study was carried out at the clinical laboratories at the Aga Khan University Hospital, Karachi from January 2003 to January 2006. PATIENTS AND METHODS: All patients irrespective of age and gender presenting with bleeding symptoms and having normal platelet count were evaluated. Demographic details, relevant clinical history along with results of complete blood count, bleeding time and platelet aggregation studies were retrieved through computerized data base and evaluated for the diagnosis of Glanzmann's thrombasthenia. RESULTS: During the study period, 50 out of 2317 patients (2.2%) were diagnosed as Glanzmann's thrombasthenia by platelet aggregometry with male to female ratio of 0.85:1 and median age of 10.2 years (ranging from 3 months to 27 years). Common symptoms were epistaxis, oral and gingival bleed, bleeding from minor cuts and trauma that were observed in 46% of the patients; while 18%, 8% and 10% of them also complained of bruising, hematuria and bleeding per rectum respectively. Majority i.e. 86% had a bleeding time greater than 10 minutes. All patients had received blood or blood products for their bleeding episodes. CONCLUSION: Platelet aggregometry is a useful diagnostic modality for the assessment of Glanzmann's thrombasthenia. The disorder presents with muco-cutaneous bleeding and was found to be a common cause of bleeding in our setup.