Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study.

Background: Bedaquiline improves treatment outcomes in patients with rifampin-resistant (RR) tuberculosis but prolongs the QT interval and carries a black-box warning from the US Food and Drug Administration. The World Health Organization recommends that all patients with RR tuberculosis receive a regimen containing bedaquiline, yet a phase 3 clinical trial demonstrating its cardiac safety has not been published.

Methods: We conducted an observational cohort study of patients with RR tuberculosis from 3 provinces in South Africa who received regimens containing bedaquiline.

Adults from Kisumu, Kenya have robust γδ T cell responses to Schistosoma mansoni, which are modulated by tuberculosis.

Schistosoma mansoni (SM) is a parasitic helminth that infects over 200 million people and causes severe morbidity. It undergoes a multi-stage life cycle in human hosts and as such stimulates a stage-specific immune response. The human T cell response to SM is complex and varies throughout the life cycle of SM.

Modeling Missing Cases and Transmission Links in Networks of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

Patterns of transmission of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases worldwide in 2017. Modeling TB transmission networks can provide insight into drivers of transmission, but incomplete sampling of TB cases can pose challenges for inference from individual epidemiologic and molecular data. We assessed the effect of missing cases on a transmission network inferred from Mycobacterium tuberculosis sequencing data on extensively drug-resistant TB cases in KwaZulu-Natal, South Africa, diagnosed in 2011-2014.

CD4 T Cells in and Co-infected Individuals Maintain Functional TH1 Responses.

(Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection.

The Impact of Concurrent Antiretroviral Therapy and MDR-TB Treatment on Adverse Events.

Background: South Africa has among the highest incidence of multidrug-resistant tuberculosis (MDR-TB) and more than 70% of patients are HIV co-infected. MDR-TB treatment is associated with frequent adverse events (AEs). Although guidelines recommend concurrent treatment of MDR-TB and HIV, safety data on concurrent therapy are limited.

Treatment Adherence Among Persons Receiving Concurrent Multidrug-Resistant Tuberculosis and HIV Treatment in KwaZulu-Natal, South Africa.

Background: Success in multidrug-resistant tuberculosis (MDR-TB) and HIV treatment requires high medication adherence despite high pill burdens, frequent adverse events, and long treatment duration, which may jeopardize adherence. We prospectively compared MDR-TB/HIV-coinfected persons to those with MDR-TB alone to determine the impact of concurrent treatment on adherence and outcomes.

Methods: We assessed medication adherence monthly using 3-day recall, 30-day recall, and visual analog scale and examined adherence to monthly study visits (months 0-12).

Social Mixing and Clinical Features Linked With Transmission in a Network of Extensively Drug-resistant Tuberculosis Cases in KwaZulu-Natal, South Africa.

Background: Tuberculosis (TB) is the leading infectious cause of death globally, and drug-resistant TB strains pose a serious threat to controlling the global TB epidemic. The clinical features, locations, and social factors driving transmission in settings with high incidences of drug-resistant TB are poorly understood.

Methods: We measured a network of genomic links using Mycobacterium tuberculosis whole-genome sequences.

Osteoid osteoma: Contemporary management.

Osteoid osteoma is a benign bone-forming tumor with hallmark of tumor cells directly forming mature bone. Osteoid osteoma accounts for around 5% of all bone tumors and 11% of benign bone tumors with a male predilection. It occurs predominantly in long bones of the appendicular skeleton.

Unicameral bone cysts: Current concepts.

Unicameral bone cysts (UBC) or simple/solitary bone cysts are benign fluid filled cavities that enlarge over time, resulting in thinning of the bone. Usually these cysts are reported in the metaphyseal areas of long bones with open physes. 85% of UBCs occur almost exclusively in children and adolescents.

Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities.

Despite evidence that transmission is driving an extensively drug-resistant TB (XDR-TB) epidemic, our understanding of where and between whom transmission occurs is limited. We sought to determine whether there was genomic evidence of transmission between individuals without an epidemiologic connection.We conducted a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the 2011-2014 period.

Spatial Patterns of Extensively Drug-Resistant Tuberculosis Transmission in KwaZulu-Natal, South Africa.

Background: Transmission is driving the global drug-resistant tuberculosis (TB) epidemic; nearly three-quarters of drug-resistant TB cases are attributable to transmission. Geographic patterns of disease incidence, combined with information on probable transmission links, can define the spatial scale of transmission and generate hypotheses about factors driving transmission patterns.

Methods: We combined whole-genome sequencing data with home Global Positioning System coordinates from 344 participants with extensively drug-resistant (XDR) TB in KwaZulu-Natal, South Africa, diagnosed from 2011 to 2014.

A High Throughput Whole Blood Assay for Analysis of Multiple Antigen-Specific T Cell Responses in Human Infection.

Antigen-specific CD4 and CD8 T cells are important components of the immune response to , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of -specific T cells correlate with infection outcome in humans. To facilitate evaluation of human -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes. We describe here the optimization and standardization of a microtiter plate-based, diluted whole blood stimulation assay utilizing overlapping peptide pools corresponding to a functionally diverse panel of 60 Ags.

Improved Survival and Cure Rates With Concurrent Treatment for Multidrug-Resistant Tuberculosis-Human Immunodeficiency Virus Coinfection in South Africa.

Background: Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone.

Methods: This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013.

Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa.

Background: KwaZulu-Natal province, South Africa, has among the highest burden of XDR TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR TB patients and proximity to health facilities in KwaZulu-Natal.

Establishing a hospital based fracture liaison service to prevent secondary insufficiency fractures.

In the aging population worldwide, osteoporosis is a relatively common condition and a major cause of long-term morbidity. Initial fragility fractures can lead to subsequent fractures. After a vertebral fracture, the risk of any another fracture increases 200% and that of a subsequent hip fracture increases 300%.

Polymorphisms in the vitamin D receptor gene are associated with reduced rate of sputum culture conversion in multidrug-resistant tuberculosis patients in South Africa.

Background: Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established.

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia.

Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.

Transmission of Extensively Drug-Resistant Tuberculosis in South Africa.

Background: Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions.

OSATS for total knee replacement: Assessment of surgical competence in the operating room.

Traditionally the surgical and technical competence of Residents has been assessed inadequately and has received little attention among the core competencies defined by the Royal College of Physicians and Surgeons of Canada\'s CanMEDS programme and the Accreditation Council for Graduate Medical Education (ACGME). With the development of novel and advanced surgical techniques with different learning curves, time pressure in busy operating rooms, and increasing complexity of cases at university hospitals, acquiring technical skills for Residents has become more challenging. Over the last two decades, methods have been developed to assess technical competence objectively.

Measles susceptibility in children in Karachi, Pakistan.

Measles, despite being vaccine preventable is still a major public health problem in many developing countries. We estimated the proportion of measles susceptible children in Karachi, the largest metropolitan city of Pakistan, one year after the nationwide measles supplementary immunization activity (SIA) of 2007-2008. Oral fluid specimens of 504 randomly selected children from Karachi, aged 12-59 months were collected to detect measles IgG antibodies.

Evolution of trauma management at a tertiary care hospital: a cohort study.

Objective: To analyze the characteristics of polytrauma patients and to assess the outcome of trauma care as this specialty has evolved over the years at a university hospital.

Methods: The study included all polytrauma patients treated between January 1998 and September 2005 at a tertiary care hospital in a megacity. Data of 1009 patients was collected prospectively and analyzed retrospectively.

Incidence of pneumonia, bacteremia, and invasive pneumococcal disease in Pakistani children.

Objective: To determine the incidence of pneumonia, bacteremia, and invasive pneumococcal disease (IPD) in Pakistani children <5 years old.

Methods: Household surveillance from 1st February 2007 to 12th May 2008 was conducted in two low-income, coastal communities of Karachi. Community health workers referred each sick child <5 years old to the local clinic.

Surgical management of neglected bilateral obligatory patella dislocation.

Congenital dislocation of the patella may present as an isolated anomaly or may be associated with other lower limb deformities as part of a more complex malformative or dystrophic syndrome. One type is the congenitally dislocated patella fixed irreducibly from birth in a lateral position, and second is the obligatory patella dislocation that is hypoplastic to start with and gradually gets fixed into the lateral position as the child grows. We report the surgical management of a 16-year-old boy with neglected obligatory dislocation of bilateral patellae with 2-year follow-up results.

Well leg compartment syndrome: the debit side of hemilithotomy position.

We describe a case of well leg compartment syndrome following unilateral lithotomy position in a patient undergoing contralateral antegrade intramedullary femoral nailing. Following two-incision four compartment fasciotomy, the patient recovered with no residual defects. We dissuade use of the hemilithotomy position for antegrade femoral nailing procedures in favour of another previously described position, because this predisposes patients to position-associated complications without offering any substantial advantage.