An observational study addressing the anatomic basis of mesosigmoidopexy as a rational treatment of non-gangrenous sigmoid volvulus

Sigmoid volvulus is a common cause of bowel obstruction. We describe mesosigmoidopexy, an accepted surgical technique for the management of non-gangrenous sigmoid volvulus, and provide anatomic correlations supporting the therapy. Mesosigmoidopexy should be considered as a rational alternative to resection and anastomosis when operating on non-gangrenous sigmoid volvulus.     

IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma

Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.     

Spatial patterns of the tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is characterized neuropathologically by neuronal loss, gliosis, and the presence of tau-immunoreactive neuronal and glial cell inclusions affecting subcortical and some cortical regions. The objectives of this study were to determine (1) the spatial patterns of the tau-immunoreactive pathology, viz., neurofibrillary tangles (NFT), oligodendroglial inclusions (GI), tufted astrocytes (TA), and Alzheimer’s disease-type neuritic plaques (NP) in PSP and (2) to investigate the spatial correlations between the histological features. Post-mortem material of cortical and subcortical regions of eight PSP cases was studied. Spatial pattern analysis was applied to the NFT, GI, TA, NP, abnormally enlarged neurons (EN), surviving neurons, and glial cells. NFT, GI, and TA were distributed either at random or in regularly distributed clusters. The EN and NP were mainly randomly distributed. Clustering of NFT and EN was more frequent in the cortex and subcortical regions, respectively. Variations in NFT density were not spatially correlated with the densities of either GI or TA, but were positively correlated with the densities of EN and surviving neurons in some regions. (1) NFT were the most widespread tau-immunoreactive pathology in PSP being distributed randomly in subcortical regions and in regular clusters in cortical regions, (2) GI and TA were more localized and exhibited a regular pattern of clustering in subcortical regions, and (3) neuronal and glial cell pathologies were not spatially correlated.     

Decreased cortical muscarinic M1 receptors in schizophrenia are associated with changes in gene promoter methylation,mRNA and gene targeting microRNA

Many studies have shown decreased cortical muscarinic M1 receptors (CHRM1) in schizophrenia (Sz), with one study showing Sz can be separated into two populations based on a marked loss of CHRM1 (∼75%) in ∼25% of people (Def-Sz) with the disorder. To better understand the mechanism contributing to the loss of CHRM1 in Def-Sz, we measured specific markers of gene expression in the cortex of people with Sz as a whole, people differentiated into Def-Sz and people with Sz that do not have a deficit in cortical CHRM1 (Non-Def-Sz) and health controls. We now report that cortical CHRM1 gene promoter methylation and CHRM1 mRNA are decrease in Sz, Def-Sz and Non-Def-Sz but levels of the micro RNA (miR)-107, a CHRM1 targeting miR, are increased only in Def-Sz. We also report in vitro data strongly supporting the notion that miR-107 levels regulate CHRM1 expression. These data suggest there is a reversal of the expected inverse relationship between gene promoter methylation and CHRM1 mRNA in people with Sz and that a breakdown in gene promoter methylation control of CHRM1 expression is contributing to the global pathophysiology of the syndrome. In addition, our data argues that increased levels of at least one miR, miR-107, is contributing to the marked loss of cortical CHRM1 in Def-Sz and this may be a differentiating pathophysiology. These latter data continue to support the hypothesis that microRNAs (miRNA) have a role in the underlying neurobiology of Sz but argue they are differentially affected in subsets of people within that syndrome.     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Survival after burn in a sub-Saharan burn unit: Challenges and opportunities

Background

Burns are among the most devastating of all injuries and a major global public health crisis, particularly in sub-Saharan Africa. In developed countries, aggressive management of burns continues to lower overall mortality and increase lethal total body surface area (TBSA) at which 50% of patients die (LA50). However, lack of resources and inadequate infrastructure significantly impede such improvements in developing countries.

Methods

This study is a retrospective analysis of patients admitted to the burn center at Kamuzu Central Hospital in Lilongwe, Malawi between June 2011 and December 2012. We collected information including patient age, gender, date of admission, mechanism of injury, time to presentation to hospital, total body surface area (TBSA) burn, comorbidities, date and type of operative procedures, date of discharge, length of hospital stay, and survival. We then performed bivariate analysis and logistic regression to identify characteristics associated with increased mortality.

Results

A total of 454 patients were admitted during the study period with a median age of 4 years (range 0.5 months to 79 years). Of these patients, 53% were male. The overall mean TBSA was 18.5%, and average TBSA increased with age—17% for 0–18 year olds, 24% for 19–60 year olds, and 41% for patients over 60 years old. Scald and flame burns were the commonest mechanisms, 52% and 41% respectively, and flame burns were associated with higher mortality. Overall survival in this population was 82%; however survival reduced with increasing age categories (84% in patients 0–18 years old, 79% in patients 19–60 years old, and 36% in patients older than 60 years). TBSA remained the strongest predictor of mortality after adjusting for age and mechanism of burn. The LA50 for this population was 39% TBSA.

Discussion

Our data reiterate that burn in Malawi is largely a pediatric disease and that the high burn mortality and relatively low LA50 have modestly improved over the past two decades. The lack of financial resources, health care personnel, and necessary infrastructure will continue to pose a significant challenge in this developing nation. Efforts to increase burn education and prevention in addition to improvement of burn care delivery are imperative.     

Sex Differences in Interpersonal Violence in Malawi: Analysis of a Hospital-Based Trauma Registry

Background

Although interpersonal violence (“assault”) exists in every society, the World Health Organization (WHO) estimated that 90 % of the exposure burden occurs in low- and middle-income countries. The objectives of this study were to define the incidence of assault-related injuries among subjects presenting for emergency room care secondary to sustained trauma in Lilongwe, Malawi; to measure the impact of sex on incidence, injury type, and care received; and to measure the effect of both sex and geographic location of the injury on time to presentation for medical care.

Methods

This is a retrospective cohort analysis of data prospectively collected in the Kamuzu Central Hospital Trauma Surveillance Registry from July 2008 to December 2010 (n = 23,625). We used univariate, bivariate, and logistic regression analyses to measure association of sex with variables of interest, and geospatial mapping to evaluate the association of location of assault on time to presentation for care.

Results

The mean age of our trauma cohort was 27.7 years. Assaults accounted for 26.8 % of all injuries. Of those assaulted, 21.0 % (1299) were female, who were younger (26.2 vs. 28.1 years, p < 0.001), more likely to arrive to the hospital by minibus (p < 0.001), and less likely to arrive by police (p < 0.001). Altogether 62 % of the females were assaulted in their homes—much more often than their male counterparts (p < 0.001). Females were more likely to sustain contusions (p < 0.001) and males more likely to have lacerations and penetrating stab wounds (p < 0.001) or head injury (p < 0.001). Females had delayed hospital presentation following assault (p = 0.001) and were more likely to be treated as outpatients after adjusting for age, injury type, and injury location (adjusted odds ratio 1.74, 95 % CI 1.3–2.3, p < 0.001). Assaults clustered geographically in the Lilongwe district. Delayed presentation of females occurred irrespective of proximity to the hospital.

Conclusions

This study brings attention to sex differences in assault victims. A prevention strategy focusing on sex roles and domestic abuse of women is paramount. Efforts are needed to stop dischargin female assault victims back into a potentially unsafe, abusive environment.     

Injury Characteristics and Outcomes in Elderly Trauma Patients in Sub-Saharan Africa

Background

Traumatic injury in the elderly is an emerging global problem with an associated increase in morbidity and mortality. This study sought to describe the epidemiology of elderly injury and outcomes in sub-Saharan Africa.

Methods

We conducted a retrospective analysis of adult patients (≥ 18 years) with traumatic injuries presenting to the Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, over 5 years (2009–2013). Elderly patients were defined as adults aged ≥65 years and compared to adults aged 18–44 and 45–64 years. We used propensity score matching and logistic regression to compare the odds of mortality between age groups using the youngest age group as the reference.

Results

42,816 Adult patients with traumatic injuries presented to KCH during the study period. 1253 patients (2.9 %) were aged ≥65 years with a male preponderance (77.4 %). Injuries occurred more often at home as age increased (25.3, 29.5, 41.1 %, p < 0.001) and falls were more common (14.1, 23.8, 36.3 %, p < 0.001) for elderly patients. Elderly age was associated with a higher proportion of hospital admissions (10.6, 21.3, 35.2 %, p < 0.001). Upon propensity score matching and logistic regression analysis, the odds ratio of mortality for patients aged ≥65 was 3.15 (95 % CI 1.45, 6.82, p = 0.0037) compared to the youngest age group (18–44 years).

Conclusions

Elderly trauma in a resource-poor area in sub-Saharan Africa is associated with a significant increase in hospital admissions and mortality. Significant improvements in trauma systems, pre-hospital care, and hospital capacity for older, critically ill patients are imperative.

     

Relationship of Height to Site‐Specific Fracture Risk in Postmenopausal Women

Height has been associated with increased risk of fracture of the neck of femur. However, information on the association of height with fractures at other sites is limited and conflicting. A total of 796,081 postmenopausal women, who reported on health and lifestyle factors including a history of previous fractures and osteoporosis, were followed for 8 years for incident fracture at various sites by record linkage to National Health Service hospital admission data. Adjusted relative risks of fracture at different sites per 10‐cm increase in height were estimated using Cox regression. Numbers with site‐specific fractures were: humerus (3036 cases), radius and/or ulna (1775), wrist (9684), neck of femur (5734), femur (not neck) (713), patella (649), tibia and/or fibula (1811), ankle (5523), and clavicle/spine/rib (2174). The risk of fracture of the neck of femur increased with increasing height (relative risk [RR] = 1.48 per 10‐cm increase, 99% confidence interval [CI] 1.39–1.57) and the proportional increase in risk was significantly greater than for all other fracture sites (p_{heterogeneity} < 0.001). For the other sites, fracture risk also increased with height (RR = 1.15 per 10 cm, CI 1.12–1.18), but there was only very weak evidence of a possible difference in risk between the sites (p_{heterogeneity} = 0.03). In conclusion, taller women are at increased risk of fracture, especially of the neck of femur. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).