Human immunodeficiency virus in Saudi Arabia: Current and future challenges.

INTRODUCTION: Understanding the pathophysiology of HIV infection has been crucial to the design of effective anti-viral strategies. HIV infection is declining worldwide due to early diagnosis and the effective long-term use of anti-retroviral therapy. New infections decreased from 3.3 million in 2002-2.3 million in 2012. However, in the Middle East and North Africa (MENA), an estimated 83,000 individuals still acquired the virus, with 37,000 morbidities reported. The first incidence of acquired immunodeficiency syndrome (AIDS) from the Kingdom of Saudi Arabia (KSA) was reported in 1984. By the end of 2013, around 1509 patients had been diagnosed with HIV infection. HIV surveillance has improved in KSA with advances in medical care, counseling, family planning, diagnostic evaluation, and anti-retroviral therapy, but challenges remain. Patients receiving anti-retroviral therapy still show significant morbidity and mortality. Further targeted treatment regimens and preventive strategies are required to control HIV infection in KSA. Progress towards meeting the 90-90-90 goals for HIV in the MENA has also not been systematically monitored. METHOD: In this review, we examine current screening programs, therapeutic modalities, the emergence of drug resistance, and future perspectives for HIV-associated health care in KSA. CONCLUSION: The aim is to offer insight for healthcare policymakers to comply with the UNAIDS 2020 vision program and help establish the prevailing paradigms in the HIV community for an AIDS-free generation and the 90-90-90 goals for diagnosis.

Endemic or regionally limited bacterial and viral infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts. In this paper, we summarise the data and provide recommendations on several endemic and regionally limited viral and bacterial infections, many of which are listed by WHO as neglected tropical diseases, including Dengue, Zika, yellow fever, chikungunya, rabies, brucellosis, melioidosis, and leptospirosis.

Endemic or regionally limited parasitic and fungal infections in haematopoietic stem-cell transplantation recipients: a Worldwide Network for Blood and Marrow Transplantation (WBMT) Review.

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.

Comparison of the safety and immunogenicity of the BNT-162b2 vaccine and the ChAdOx1 vaccine for solid organ transplant recipients: a prospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.

Data-Driven Prediction for COVID-19 Severity in Hospitalized Patients.

Clinicians urgently need reliable and stable tools to predict the severity of COVID-19 infection for hospitalized patients to enhance the utilization of hospital resources and supplies. Published COVID-19 related guidelines are frequently being updated, which impacts its utilization as a stable go-to resource for informing clinical and operational decision-making processes. In addition, many COVID-19 patient-level severity prediction tools that were developed during the early stages of the pandemic failed to perform well in the hospital setting due to many challenges including data availability, model generalization, and clinical validation. This study describes the experience of a large tertiary hospital system network in the Middle East in developing a real-time severity prediction tool that can assist clinicians in matching patients with appropriate levels of needed care for better management of limited health care resources during COVID-19 surges. It also provides a new perspective for predicting patients' COVID-19 severity levels at the time of hospital admission using comprehensive data collected during the first year of the pandemic in the hospital. Unlike many previous studies for a similar population in the region, this study evaluated 4 machine learning models using a large training data set of 1386 patients collected between March 2020 and April 2021. The study uses comprehensive COVID-19 patient-level clinical data from the hospital electronic medical records (EMR), vital sign monitoring devices, and Polymerase Chain Reaction (PCR) machines. The data were collected, prepared, and leveraged by a panel of clinical and data experts to develop a multi-class data-driven framework to predict severity levels for COVID-19 infections at admission time. Finally, this study provides results from a prospective validation test conducted by clinical experts in the hospital. The proposed prediction framework shows excellent performance in concurrent validation (n=462 patients, March 2020-April 2021) with highest discrimination obtained with the random forest classification model, achieving a macro- and micro-average area under receiver operating characteristics curve (AUC) of 0.83 and 0.87, respectively. The prospective validation conducted by clinical experts (n=185 patients, April-May 2021) showed a promising overall prediction performance with a recall of 78.4-90.0% and a precision of 75.0-97.8% for different severity classes.

Quantitative proteomics analysis reveals unique but overlapping protein signatures in HIV infections.

BACKGROUND: Human immunodeficiency virus-1 (HIV-1) exploits human host factors to complete its life cycle. Hence, discovery of HIV-regulated host proteins markers would better our understanding of the virus life-cycle and its contribution to pathogenesis and discovery of objective diagnostic and prognostic molecules. METHODS: We conducted holistic total proteomics analysis of three closely related study populations including patients with HIV type-1 (HIV-1) and HIV type-2 (HIV-2) as well as HIV-1 elite controllers (HIV-1-EC). Peripheral blood plasma (PBP) samples were subjected to label-free quantitative liquid-chromatography tandem mass-spectrometry (LC-MS/MS). RESULTS: Over 314 unique PBP protein species were identified of which 100 (approx. 32%) were significantly differentially expressed (≥2 to ∞ - fold-change; p < 0.05) between the three sample cohorts. Of the 100 proteins, 91 were significantly changed between pairs of HIV-1 versus HIV-1-EC, while 83 of the 100 proteins differed significantly between HIV-2 and HIV-1-EC. Interestingly, 76 proteins (87.5%) overlap between the two data sets indicating that majority of these proteins share similar expression changes between HIV-1 and HIV-2 sample groups. Two of the identified proteins, XRCC5 and PSME1, were implicated in the early phase of the pathway network for HIV life cycle, while others were involved in infectious disease and disease of signal transduction. Among them were MAP2K1, RPL23A, RPS3, CALR, PRDX1, SOD2, LMNB1, PHB, and FGB. Despite the high degree of similarity in protein profiles of HIV-1 and HIV-2, six proteins differed significantly including ETFB, PHB2, S100A9, LMO2, PPP3R1 and Vif, a fragment of virion infectivity factor of HIV-1. Additionally, 15 proteins were uniquely expressed, and one of them (LSP1) is present only in HIV-1-EC but absent in HIV1 and HIV-2 and vice versa for the rest 14 proteins. CONCLUSIONS: Altogether, we have identified HIV-specific/related protein expression changes that might potentially be capable of early diagnosis and prognosis of HIV diseases and other related infectious diseases.

Clinical manifestations and treatment outcomes of human brucellosis at a tertiary care center in Saudi Arabia.

BACKGROUND: Brucellosis, which has profound public health and economic consequences, is endemic to Saudi Arabia. Brucella is transmitted to humans by direct contact with infected animals or by consumption of unpasteurized dairy products. Manifestations of brucellosis are protean and require a combination of drugs to prevent the emergence of resistance. The WHO recommends the use of doxycycline with rifampicin or an aminoglycoside for brucellosis, but experts in Saudi Arabia prefer to avoid the use of rifampicin and aminoglycosides to lessen the possibility of emergence of drug-resistant tuberculosis. OBJECTIVES: Compare rifampicin and doxycycline in the treatment of human brucellosis versus various combinations of doxycycline, with either trimethoprim-sulfamethoxazole (co-trimoxazole), quinolones or aminoglycosides, and describe the clinical manifestations of brucellosis. DESIGN: Retrospective medical record review. SETTING: Single tertiary care center. PATIENTS AND METHODS: Diagnosis of brucellosis was based on positive serology by standard agglutination test (SAT), or isolation by culture of Brucella species from blood, body fluid or tissue. MAIN OUTCOME MEASURES: Cure rate with the use of doxycycline in combination with either co-trimoxazole, quinolone or aminoglyco-sides in comparison to doxycycline/rifampicin and the clinical features of brucellosis. SAMPLE SIZE: 123. RESULTS: In 118 (96%) patients, the median IgG/IgM antibody titers at diagnosis and at 6 and 12 months were 1:1280/1:1280, 1:640/1:640, and 1:320/1:160, respectively. There were no differences in outcome between treatment regimens, as evidenced by a significant decrease in SAT titers and symptom resolution within six months. Five (4%) patients relapsed from non-adherence to treatment, but responded well to a second course of treatment. Blood cultures were positive in 50 patients (41%) patients. Fever, arthralgia and back pain were the most common symptoms. Good serological and clinical responses were achieved in 96% of patients. Relapse in 4% (n=5) was due to self-reported non-adherence. LIMITATIONS: Retrospective, relatively small sample size. CONCLUSIONS: Doxycycline with co-trimoxazole is as efficacious as doxycycline/rifampicin in non-focal brucellosis and is preferred in countries with a high prevalence of tuberculosis. CONFLICT OF INTEREST: None.

Nocardiosis at an Organ Transplant Center in Saudi Arabia: 15 years' experience.

BACKGROUND: Nocardiosis is a rare infection that affects immunocompromised patients on immunosuppressive medications used for transplantation and cancer therapy. Such therapies are becoming more widely available in the Middle East region. Yet, reports on nocardiosis are scarce. MATERIALS AND METHODS: This was a retrospective analysis of patients who were diagnosed with nocardiosis from 2004 to 2018 at a transplantation and cancer center. Nocardiosis were defined per the European Organization for Research and Treatment of Cancer criteria. RESULTS: During the study period, 35 patients with nocardiosis (male: 68.5%) were identified. The most common underlying associated condition was transplantation 11 (31.4%), followed by malignancy 7 (20%), connective tissue disease and sarcoidosis 7 (20%), chronic lung disease 5 (14%), miscellaneous conditions 4 (11%), and one patient with human immunodeficiency virus. Nocardia was disseminated in 8 patients (22.9%) and isolated in 27 (77.1%); the latter included 13 patients (37.1%) with bronchial form, 11 (31.4%) with isolated visceral form, and 3 (8.6%) with cutaneous form. Pulmonary involvement occurred in 90% of the cases with cough, fever, and dyspnea being the most common symptoms. The main strain isolate was Nocardia asteroides, and the cure rate was 90%. Mortality related to nocardiosis occurred in 3 transplant patients (8.6%). CONCLUSION: Wider use of immunosuppressive therapy warrants vigilance to nocardiosis, which can present in a myriad of clinical forms. In our series, mortality was confined to the transplantation group, probably because of the relatively heavy immunosuppression. Nonetheless, prognosis is favorable if the infection is recognized and treated early.

Successful Use of Rifamycin-Sparing Regimens for the Treatment of Active Tuberculosis in Lung Transplant Recipients.

OBJECTIVES: Tuberculosis is an important opportunist infection that can complicate the posttransplant course of solid-organ transplant recipients. Lung transplant recipients are at higher risk of tuberculosis after transplant than are other solid-organ transplant recipients. Significant drug-drug interactions between antituberculous medications, especially rifampin, and immunosuppressant medications render treatment in this patient population especially challenging. Data on the management of tuberculosis in lung transplant recipients with rifamycin-sparing regimens are so far limited. Therefore, we evaluated the incidence, clinical features, treatment, and outcomes of active tuberculosis in lung transplant patients from a single center in Riyadh, Saudi Arabia. MATERIALS AND METHODS: Cases of active tuberculosis in lung transplant recipients diagnosed between January 2005 and December 2017 at our center were included. Data on patient demographics, clinical presentations, diagnosis, treatment regimens, and outcomes were collected. RESULTS: Seven of 133 lung transplant recipients (5.3%) were diagnosed with active tuberculosis during the study period, corresponding to an incidence rate of 2147/100 000 person-years. Patients were diagnosed at median time of 94 days posttransplant. Fever and weight loss were the most common presenting symptoms. All patients were initially treated with a regimen consisting of isoniazid, ethambutol, pyrazinamide, and moxifloxacin. Isoniazid was later substituted with rifabutin in 2 patients with isoniazid-resistant tuberculosis. All patients were treated for a total of 9 to 12 months, without any adverse event-related interruptions. All patients were alive at 12 months after the diagnosis of tuberculosis. There was no evidence of relapse in any of the patients after a median of 32 (range, 9-51) months of follow-up after treatment. CONCLUSIONS: Rifamycin-sparing regimens appear to be safe and highly efficacious in the treatment of active tuberculosis in lung transplant recipients.

HIV in the Kingdom of Saudi Arabia: Can We Change the Way We Deal with Co-Infections.

The first incidence of acquired immunodeficiency syndrome (AIDS) from the Kingdom of Saudi Arabia (KSA) was reported back in 1984, and by the end of 2013, around 1509 patients were diagnosed with HIV infection. Recently in 2018, the Saudi ministry of health released that the incidence of HIV in Saudi Arabia is 3 cases of HIV for every 10,000 of the population. Having said that, the surveillance of HIV will face a range of challenges in KSA despite proper medical care, counseling, family planning, diagnostic, evaluation, and the use of effective anti-retroviral therapy. Patients who underwent anti-retroviral therapy showed significant reduction in morbidity as well as mortality. On the other hand, further targeted treatment and preventive strategies are warranted to control HIV co-infections in the KSA. In addition, progress towards meeting the WHO 90-90-90 goals for HIV not only at KSA but at the MENA region too, which is that of the population, 90% are diagnosed, 90% undergoing treatment, and 90% under viral control, is not being systematically monitored. In this review, we discuss the common co-infections with HIV infections that are reported in KSA, which when compared to international trends, it is similar for both viral hepatitis and tuberculosis. Although those co-infections exist, they are presented in different ratios and percentages when compared to the international reported data. These differences mandates defining and introducing new resilient methods of treatment and preventive measures. In this review, we offer an insight into healthcare policymakers to be compliant with UNAIDS 2020 vision program. We also discuss some of the gaps and recommendations to achieve the WHO 90-90-90 goal.

Mycobacterium tuberculosis DNA in living donor transplanted livers and donor-related tuberculosis in recipients: A retrospective longitudinal cohort study.

OBJECTIVES: Mycobacterium tuberculosis DNA has been detected in multiple organs in people without active tuberculosis or a history of tuberculosis. Molecular testing for metabolic activity has suggested that M tuberculosis DNA represents viable bacilli. Whether transplanted organs with M tuberculosis DNA can result in tuberculosis in recipients has not been assessed. METHODS: Biopsies obtained at the time of living donor liver transplantation were tested for the presence of M tuberculosis DNA using in situ PCR. The cohort of recipients was longitudinally followed for the development of tuberculosis. RESULTS: Living donor liver transplantation was performed for 270 patients. Mean age was 33 years (median: 41 years, range: 1-80 years). Recipients were followed for a mean of 68 months (median: 72 months, range: 1-138 months) after transplantation. Mycobacterium tuberculosis DNA was detected in 25 of 155 donated livers (16%) with liver biopsies available for testing. None of the recipients of these livers received tuberculosis chemoprophylaxis and only one (4%) developed tuberculosis 15 months after transplantation. Among the entire cohort of 270 patients, post-transplant tuberculosis was diagnosed in four patients (1.48%) at an incidence rate of 2.61 cases per 1000 transplant-years. No factors associated with developing tuberculosis were identified, including positive M tuberculosis DNA in transplanted livers. CONCLUSIONS: Mycobacterium tuberculosis DNA in living donor transplanted livers did not result in tuberculosis despite post-transplant immunosuppression.

Family cluster of multi-drug resistant tuberculosis in Kingdom of Saudi Arabia.

We describe the clinical and genetic characteristics of multi-drug resistant tuberculosis (MDR-TB) in a family cluster in the western region of Kingdom of Saudi Arabia diagnosed between 2012 and 2016. All cases had risk factors for tuberculosis acquisition and they were not household contacts of the index case. Genetic analysis detected both MDR-TB and pre-extensively drug-resistant tuberculosis (pre-XDR TB) strains in the index case and confirmed tuberculosis transmission between two cases. Lack of early diagnosis of MDR-TB by molecular testing and lack of extended contact tracing contributed to the transmission of MDR-TB among this family cluster over four years.

Demographic risk factors for extra-pulmonary tuberculosis among adolescents and adults in Saudi Arabia.

Despite low infectious potential of extrapulmonary tuberculosis (EPTB), it poses significant clinical challenges in terms of diagnosis and treatment monitoring. Understanding the main demographical risk factors for disease characteristics of EPTB plays a crucial role in speeding up diagnosis process and improving overall clinical experience. The aim of this study was to investigate the main demographical and clinical risk factors for EPTB among adults and adolescents for the first time in Saudi Arabia. A cross-sectional multicenter study was carried out on a collection of 902 extrapulmonary Mycobacterium tuberculosis complex (MTBC) isolates with demographical and clinical data. All isolates were subjected to spoligotyping and 24-loci based MIRU-VNTR typing. The association between two potential variables was assessed using odd ratios (OR) calculations. Independent risk factors for EPTB and diseases characteristics of EPTB were identified using multivariate regression model analyses. Gender was found to be significantly associated with lymph node, gastrointestinal, central nervous system and urogenital TB. Lymph node TB showed statistical association to age group below 25 years, non-Saudis and South East Asian ethnicity. While gastrointestinal TB demonstrated an association with patients above 60 years old, and Saudis. Multivariate analysis showed that gender is an independent risk factor to urogenital TB (p 0.03) and lymph node TB (p 0.005). On the other hands, South Asian (p 0.01) and South East Asian (p 0.03) ethnicities were both identified as independent risk factors significantly associated with EPTB. MTBC lineages, site of infections, gender, HIV and smear positivity showed no significant association. Nationwide qualitative-studies are highly warranted in the future to further understand the main demographic risk factors for disease characteristics of EPTB.

Pneumocystis jiroveci Pneumonia in HIV-Positive and HIV-Negative Patients: A Single-Center Retrospective Study.

BACKGROUND: To describe the clinical presentations, treatment regimen, and outcomes of Pneumocystis jiroveci pneumonia (PJP) among immunocompromised patients at King Faisal Specialist Hospital and Research Center in Saudi Arabia. MATERIALS AND METHODS: In this retrospective cohort study, patients with a laboratory-confirmed diagnosis of PJP were included. RESULTS: During the study, 42 patients with confirmed PJP were identified. Twenty (48%) patients were HIV-infected, while 22 (52%) were HIV negative. The median T-cell count (CD 4 ) was below 50 cells/mL in HIV patients with PJP at the time of HIV and PJP diagnoses. Graft rejection, cytomegalovirus (CMV) reactivation, and lymphopenia were associated with the development of PJP in transplant recipients; and high-dose steroids for non-transplant patients. The all-cause mortality at 90 days was lower in individuals with HIV-related PJP, compared to those with other predisposing conditions (10% and 32%, respectively; P=0.085). No specific risk factors were independently associated with the increased risk of mortality. CONCLUSION: PJP remains an important cause of morbidity and mortality in immunocompromised patients, with a higher mortality rate reported in non-HIV patients.

Impact of Mycobacterium tuberculosis complex lineages as a determinant of disease phenotypes from an immigrant rich moderate tuberculosis burden country.

BACKGROUND: Growing evidences suggested that the Mycobacterium tuberculosis complex (MTBC) lineages can determine the clinical outcome of pulmonary and extra-pulmonary tuberculosis. However, limited data only available revealing such association of bacterial genotypes and clinical phenotypes from immigrant rich countries. METHODS: A multicenter study has been carried out on a collection of 2092 (1003 extrapulmonary and 1089 pulmonary) MTBC isolates. Genotyping of all the isolates were carried out by spoligotyping and 24 loci based MIRU-VNTR typing. RESULTS: Demographically domination of young Saudi nationals (61.4%) and men (61.2%) were found in this cohort. Lymph nodes (62.4%) and gastrointestinal sites (16.7%) were the most common anatomical sites of infection. The predominant lineages were Delhi/CAS (26.9%), EAI (14.2%) and Ghana (9.9%). Mycobacterium africanum type I and II were reported for the first time in the country among extrapulmonary cases. 'Ancestral' lineages M.bovis (OR-5.22; 95% CI-2.23-8.22, p- < 0.001) and Delhi/CAS (OR-0.57; 95% CI-0.411-0.734, p- < 0.001) were directly associated with lymph node tuberculosis and gastrointestinal tuberculosis (M. bovis-OR-0.33; 95% CI-0.085-0.567, p-0.001 and Delhi/CAS-OR-1.87; 95% CI-1.22-2.53, p- < 0.001) respectively. Among the 'Modern' lineages, EAI showed significant association to central nervous system tuberculosis (OR-1.98; 95% CI-0.76-3.19, p-0.04) and Uganda-I to gastrointestinal tuberculosis (OR-2.41; 95% CI-0.77-4.06, p-0.02). CONCLUSIONS: The findings substantially contribute to the emerging evidences that MTBC lineages influence disease phenotypes and epidemiological consequences.

Antiretroviral resistance in HIV-1 patients at a tertiary medical institute in Saudi Arabia: a retrospective study and analysis.

BACKGROUND: Since the early 90's antiretroviral drugs have been available at King Faisal Specialist Hospital and Research Centre (KFSH&RC), a referral hospital in Riyadh, Saudi Arabia, for the treatment of both adults and children infected with HIV-1. However, up to date, there are no genetic profiling data for the resistance-causing mutations in HIV-1 virus in patients on antiretroviral drugs therapy. This paper presents an initial report and a profiling survey of drug resistance-associated mutations of 103 HIV-1 patients seen at KFSH&RC. METHODS: This is a retrospective study on Patients treated at KFSH&RC since 2003 up to 2016. The analysis was done on the drug resistance mutations profiles of 103 patients who were undergoing highly active antiretroviral therapy protocols. RESULTS: Our analysis shows that the drug resistance mutations reported in our treatment cohort of HIV-infected adults patients is similar what is internationally reported to some extent. Additionally, we have identified novel drug resistance causing mutations. Furthermore, different profile of drug resistance causing mutations was also observed. CONCLUSION: Patients showed both similar and new drug resistant causing mutations, early identification of these mutations is crucial to guide and avoid failure future therapy.

Benefit of Intraoperative Neurophysiological Monitoring in a Pediatric Patient with Spinal Dysmorphism, Split Cord Malformation, and Scoliosis.

Intraoperative neurophysiological monitoring (IONM) consists of a group of neurodiagnostic techniques that assess the nervous system's functional integrity during surgical operations. A retrospective analysis of a pediatric female patient was conducted who underwent 12 operations for the correction of scoliosis, tethered cord, and split spinal cord wherein IONM played an important role. From age 3 to 6, she underwent six procedures including a release of the tethered cord, resection of the filum terminale, removal of a T11-T12 bony spur, release of L3 adhesions, repair of subcutaneous meningocele, and correction of scoliosis with a vertical expandable prosthetic titanium rod (VEPTR) technique without the use of IONM. However, a multimodality IONM protocol with somatosensory evoked potentials, transcranial electrical motor evoked potentials (TCeMEP), and an electromyogram was utilized during the later procedures. At age 6 (the seventh procedure), a VEPTR expansion was performed, with loss and recovery of the lower extremity motor evoked potentials. The postoperative magnetic resonance imaging (MRI) showed a partial split cord malformation with retethering of the spinal cord. We repaired her split cord malformation and tethered cord while employing IONM. Using IONM for her operation was crucial because a sudden significant loss of TCeMEP resulted in a cancellation of the procedure; the MRI showed a thick remnant attached to the spinal cord. If the procedure was performed without IONM, we could have missed the underlying pathology, an error that may have resulted in paraplegia. We strongly recommend using IONM during high-risk surgical procedures to help significantly reduce the risk of permanent postoperative complications.

The Saudi Thoracic Society guidelines for diagnosis and management of noncystic fibrosis bronchiectasis.

This is the first guideline developed by the Saudi Thoracic Society for the diagnosis and management of noncystic fibrosis bronchiectasis. Local experts including pulmonologists, infectious disease specialists, thoracic surgeons, respiratory therapists, and others from adult and pediatric departments provided the best practice evidence recommendations based on the available international and local literature. The main objective of this guideline is to utilize the current published evidence to develop recommendations about management of bronchiectasis suitable to our local health-care system and available resources. We aim to provide clinicians with tools to standardize the diagnosis and management of bronchiectasis. This guideline targets primary care physicians, family medicine practitioners, practicing internists and respiratory physicians, and all other health-care providers involved in the care of the patients with bronchiectasis.

Mycobacterium tuberculosis in solid organ transplantation: incidence before and after expanded isoniazid prophylaxis.

BACKGROUND: The risk of tuberculosis is increased in solid organ transplantation. Rates remain high in developed and developing countries. We developed protocols to better identify transplant recipients at risk of tuberculosis and initiate interventions to prevent tuberculosis. OBJECTIVES: Report tuberculosis incidence in solid-organ transplant recipients and the results of expanded isoniazid prophylaxis in deceased-donor renal transplantation. DESIGN: Retrospective cohort study, comparing two time periods. SETTING: Large transplantation center in a WHO-medium endemicity country for tuberculosis. METHODS: In a cohort of all solid-organ transplant recipients performed between 2003 and 2012, tuberculosis-free transplantation follow-up is used for incidence calculation. Rates of tuberculosis in renal transplant recipients are compared before and after implementation of expanded isoniazid prophylaxis. MAIN OUTCOME MEASURE(S): Active tuberculosis post-transplantation. RESULTS: Of 1966 solid-organ transplant recipients (kidney: 1391, liver: 426, heart: 114, lung: 35), 20 recipients (1.02%) developed tuberculosis. Twelve cases (60%) developed tuberculosis within one year of transplantation. The incidence was 248 cases per 100 000 transplant-years. The proportion of transplant recipients (incidence of tuberculosis per 100 000 transplant-years) for specific organs were kidney 0.58% (127), liver 1.88% (594), heart: 1.75% (570), and lung 5.71% (4750). In the survival analysis, lung transplant recipients had significantly higher rates of tuberculosis compared to recipients of kidneys from living donors (P=.0001) with a rate ratio of 45.3 (95% CI: 7-313). Mortality was 5% among tuberculosis patients. After implementing expanded isoniazid prophylaxis among deceased-donor kidney recipients, no tuberculosis occurred in 177 recipients, compared to 3 out of 155 (2%) recipients before implementation. CONCLUSIONS: Rates of tuberculosis among our solid transplant recipients are decreasing. Universal iso-niazid prophylaxis in transplant recipients could reduce transplant-associated tuberculosis in endemic areas. LIMITATIONS: Donor data on tuberculosis exposure and prevention and tuberculosis prevention efforts before referral to our center are not available for all patients.

Diagnostic potential of interferon-gamma release assay to detect latent tuberculosis infection in kidney transplant recipients.

BACKGROUND: Latent tuberculosis (TB) infection (LTBI) is screened by using clinical assessment, tuberculin skin test (TST), chest radiography, and recently by interferon-gamma release assays (IGRA). The objective of this study was to evaluate the diagnostic potential of QuantiFERON® -TB Gold In-Tube test (QFT) for diagnosing LTBI in patients planned for kidney transplantation. METHODS: All adult patients with end-stage renal disease, evaluated for kidney transplantation in a referral center from August 2008 till May 2013, were enrolled, after consenting in a prospective, observational, non-interventional study. LTBI diagnosis was conducted by TST, chest x-ray, and clinical assessment, followed by IGRA by QFT. RESULTS: Overall, 278 patients were enrolled and kidney transplantation was performed in 173 patients. Contributed follow-up was 836.5 patient-years, and TB-free transplant duration was 478.5 patient-years. By standard methods, LTBI was diagnosed in 14 patients. Peri-transplant chemoprophylaxis was given to 53 patients, which included recipients of organs from all deceased donors and living donors with LTBI. QFT was positive in 70 patients, negative in 200 patients, and indeterminate in 8 patients. The agreement between LTBI diagnosis using standard methods and IGRA by QFT was poor (kappa: 0.089+0.046, P-value=.017). Twenty-seven of the QFT-positive patients were transplanted and only one was given isoniazid preventive therapy. None of the transplant recipients developed TB after a median follow-up of 25 months (range 2-58 months, mean 27 months). CONCLUSIONS: The agreement of the QFT with standard diagnosis of LTBI in kidney transplant recipients was poor.