Mycobacterium tuberculosis Complex Lineage 3 as Causative Agent of Pulmonary Tuberculosis, Eastern Sudan1.

Pathogen-based factors associated with tuberculosis (TB) in eastern Sudan are not well defined. We investigated genetic diversity, drug resistance, and possible transmission clusters of Mycobacterium tuberculosis complex (MTBC) strains by using a genomic epidemiology approach. We collected 383 sputum specimens at 3 hospitals in 2014 and 2016 from patients with symptoms suggestive of TB; of these, 171 grew MTBC strains. Whole-genome sequencing could be performed on 166 MTBC strains; phylogenetic classification revealed that most (73.4%; n = 122) belonged to lineage 3 (L3). Genome-based cluster analysis showed that 76 strains (45.9%) were grouped into 29 molecular clusters, comprising 2-8 strains/patients. Of the strains investigated, 9.0% (15/166) were multidrug resistant (MDR); 10 MDR MTBC strains were linked to 1 large MDR transmission network. Our findings indicate that L3 strains are the main causative agent of TB in eastern Sudan; MDR TB is caused mainly by transmission of MDR L3 strains.

[Urinary incontinence after HOLEP: Incidence, evolution and predictive factors]. / Incontinence urinaire après énucléation endoscopique de la prostate au laser Holmium : fréquence, évolution, et facteurs prédictifs de survenue.

OBJECTIVE: Assess the early morbidity after HOLEP, the urinary incontinence in particular, and specify its different types, evolution, and predictive factors. PATIENTS AND METHODS: We conducted an observational, analytical, retrospective, monocentric study including all patients undergoing surgery for benign prostatic hypertrophy (HBP) by HoLEP between November 2015 and January 2017. The data were collected pre-, per- and postoperatively. The follow-up was for 6 months. RESULTS: One hundred and seventy one patients were included. 23 patients (14.6%) had a complication according to Clavien-Dindo classification [4]: 19 (83%) Clavien 2, 1 (4%) Clavien 3b et 3 (13%) Clavien 4. At one month of the surgery, 64 (42.7%) patients had urinary incontinence of which 55 (86.1%) presented pure stress urinary incontinence. 18 (32.7%) were still incontinent at 6 months of the surgery. The delivered amount of energy during the surgery and the preoperative IIEF5 score were statistically significantly associated with the occurrence rate of stress urinary incontinence. There was no correlation between the surgeon's learning curve and the occurrence of incontinence. CONCLUSION: The occurrence rate of urinary incontinence post HoLEP might be related to the adopted surgical technique ; It is crucial to keep the patient well informed of the risk of this complication postoperatively. LEVEL OF EVIDENCE: 4.

Statistical controversies in clinical research: end points other than overall survival are vital for regulatory approval of anticancer agents.

There is an ongoing debate about the relative merits of overall survival (OS) and other metrics that can be used as primary end points in cancer clinical trials. Although survival time is arguably the most objective metric for assessing the efficacy of anticancer treatment, OS as a clinical-trial end point needs to be conceptually distinguished from increased survival time as a goal desired by patients, clinicians and public-health policy makers. OS presents several drawbacks as a primary end point that threatens to hamper further drug development, including the increase in the number of patients and the much longer follow-up required in a clinical trial. In many settings of first-line therapy for metastatic disease, median OS is currently two to four times longer than median progression-free survival. As a result, the analysis of OS may be increasingly confounded by the effect of salvage therapies used after disease progression. In this review, we use straightforward statistical reasoning and examples from the oncology literature to argue that OS should no longer be the primary end point of most future phase III cancer clinical trials that aim at assessing the efficacy of novel therapies in the setting of metastatic disease.

Early Results of Brachial Arterio-Arterial Prosthetic Loop (AAPL) for Hemodialysis.

BACKGROUND: Vascular access has always been the Achilles heel of hemodialysis. Advances in health care have brought forward patients requiring treatment who have no veins suitable for creation of arteriovenous fistula (AVF) or insertion of central venous catheters. Use of an artery as permanent vascular access has been reported by many authors. This study reports brachial AAPL as an efficient and safe access for hemodialysis patients with central venous occlusion. METHODS: Between January 2011 and December 2014, 35 brachial arterio-arterial prosthetic loops (AAPL) were created. The age of patients ranged between 27 and 72 years, with a mean age of 52.8 years. RESULTS: The primary patency rates were 87.9%, 70.4%, and 38.8% at 12, 24, and 36 months, respectively. The secondary patency was 90.7%, 80.3%, and 67.6% at 12, 24, and 36 months, respectively, after successful thrombectomy in seven cases. CONCLUSION: Mid-term follow-up results demonstrate patency rates comparable with those of the synthetic AVF. The rate of complications, although slightly higher than that with traditional synthetic AVF, is still acceptable in this population with no option for access.

Pentavalent technetium-99m-dimercaptosuccinic acid [Tc-99m (V) DMSA] brain SPECT: does it have a place in predicting survival in patients with glioblastoma multiforme?

Pentavalent technetium-99m dimercaptosuccinic acid (Tc-99m (V) DMSA) is reported as a useful tool for detection of residual or recurrent gliomas. We aimed to investigate the prognostic value of Tc-99m (V) DMSA brain SPECT in patients with glioblastoma multiforme (GBM). 40 patients [21 males and 19 females; mean age 48.6 ± 12.2 years] with GBM were included. Tc-99m (V) DMSA brain SPECT was done after surgery and before onset of radiation therapy or chemotherapy (Baseline study), at 4-6 weeks and at 6 months as a follow-up after therapy. The end point of the study was clinical follow-up for 2 years and/or death. 4-6 weeks after therapy, 40 and 60 % had negative and positive Tc-99m (V) DMSA for viable tumor tissues respectively (P = 0.09). At 6 months follow-up, 62.5 % of (V) DMSA negative patients and 12.5 % of the positive subjects were responders (P = 0.001). The median over-all survival (OS) of all patients was 12.3 month [range 5-24 month]. Patients with positive (V) DMSA had worse survival (8.87 month) compared to the negative ones (16.67 month) (P = 0.0001). Multivariate Cox regression analysis showed that Tc-99m (V) DMSA brain SPECT studies at 4-6 weeks and 6-months follow-up were independent prognostic factors for survival [OR 1.069; 95 % CI 1.417-2.174; P = 0.03 and OR 1.055; 95 % CI 0.821-1.186; P = 0.01 respectively]. Stratification of tumors into risk groups based on prognostic parameters may improve outcome by altering or intensifying treatment methods. Technetium-99m dimercaptosuccinic acid brain SPECT may have an additional prognostic role in patients with GBM which needs further evaluation in larger future series.

Anthracyclines and taxanes in the neo/adjuvant treatment of breast cancer: does the sequence matter?

BACKGROUND: In early breast cancer, adjuvant chemotherapy decreases the risks of recurrence and breast cancer mortality, and neoadjuvant treatment leads to equivalent long-term outcomes. A large number of clinical trials have attempted to refine systemic therapeutic strategies in early breast cancer, but little attention has been paid to the sequence of anthracyclines and taxanes. Based on preclinical observations, there is limited rationale to administer the taxane before the anthracycline. METHODS: We searched PubMed, the American Society of Clinical Oncology website, and clinicaltrials.gov with the goal of identifying published or ongoing studies that aimed at comparing reverse sequences of anthracyclines and taxanes. Given the nature and the small number of studies identified, we did not attempt to quantitatively pool the study results. RESULTS: We retrieved seven studies in the adjuvant setting and eight in the neoadjuvant setting: 10 randomized trials (only 2 were phase IIII), 3 retrospective studies, and 2 ongoing phase II trials. A total of nearly 5000 patients were included in such studies. None of the clinical trials has shown disadvantages in terms of efficacy or toxicity for sequences in which the taxane was administered first. In the neoadjuvant setting, studies have collectively shown similar or increased pathological complete response rates for sequences in which the taxane was administered first. CONCLUSION: Given the available information, there seems to be sufficient evidence to suggest that a taxane followed by an anthracycline is a sequence option that can be incorporated into daily clinical practice.

Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Eco-friendly degradation of reactive red 195, reactive blue 214, and reactive yellow 145 by Klebsiella pneumoniae MW815592 isolated from textile waste.

The water is used in many textile manufacturing steps beyond cleaning. The quantity and the significant chemical load of the effluents generated constitute the primary challenge of the textile industry. In order to discover new sustainable methods to overcome this problem, the aim of this research was to study the potential for degradation of Reactive Blue 214, Reactive Red 195, and Reactive Yellow 145 using a dye degrading bacterium. Sequencing analysis reveals it to be Klebsiella pneumoniae MW815592. This strain completely decolorized artificial effluent (200 mg/L) after 42 h at pH 9 and 46 °C. The decolorization rate increased in the presence of glucose and yeast extract (2 g). In addition, our finding revealed that the decolorization is due to biodegradation rather than adsorption on the bacterial surface.

Microbiological evaluation of different strategies for management of snakes in captivity.

Keeping snakes in captivity to produce venom for scientific research and production of inputs is now a worldwide practice. Maintaining snakes in captivity involves capture, infrastructure investments, management techniques, and appropriate qualified personnel. Further, the success of the project requires knowledge of habitat, nutrition, and reproduction, and control of opportunistic infections. This study evaluated the management of snakes in three types of captivity (quarantine, intensive, and semiextensive) and diagnosed bacterial and fungal contaminants. A bacteriological profile was obtained by swabbing the oral and cloacal cavities, scales, and venoms of healthy adult snakes from Bothrops jararaca (Bj) and Crotalus durissus terrificus (Cdt). There was predominance of Enterobacteriaceae, especially non-fermenting Gram-negative bacilli excluding Pseudomonas spp and Gram- positive bacteria. Statistically, intensive captivity resulted in the highest number of bacterial isolates, followed by recent capture (quarantine) and by semiextensive captivity. No statistical difference was found between Bj and Cdt bacterial frequency. In vitro bacterial susceptibility testing found the highest resistance against the semisynthetic penicillins (amoxicillin and ampicillin) and highest sensitivity to amicacin and tobramycin aminoglycosides. To evaluate mycological profile of snakes from intensive captivity, samples were obtained from two healthy Bj and one B. moojeni, one B. pauloensis, and one Cdt showing whitish lesions on the scales suggestive of ringworm. Using conventional methods and DNA-based molecular procedures, five samples of Trichosporon asahii were identified. Despite the traditional role of intense captivity in ophidian venom production, semiextensive captivity was more effective in the present study by virtue of presenting superior control of bacterial and fungal transmission, easier management, lowest cost, and decreased rate of mortality; therefore, it should be considered as a good alternative for tropical countries.

The geography of clinical cancer research: analysis of abstracts presented at the American Society of Clinical Oncology Annual Meetings.

BACKGROUND: The American Society of Clinical Oncology Annual Meeting is the largest forum for presentation of clinical research in oncology. We quantified the contribution of countries and assessed correlates of their presence at such meetings. METHODS: After stratifying abstracts according to category of presentation (oral, poster, and 'publication only'), we took a random sample of 10% of the studies presented at years 2001-2003 and 2006-2008. We assigned abstract nationality using the affiliation of authors. For multinational studies, we developed an algorithm to assign nationality. RESULTS: Of the 22 045 eligible abstracts, 2206 were analyzed and represented 71 countries: 905 (41%) abstracts were from a single institution, 969 (44%) were multicenter, uninational studies, and 332 (15%) were multinational studies. United States nationality was assigned to 49% of all abstracts and the next 14 countries with a higher number of studies accounted for 41%. There was a statistically significant temporal trend in the proportion of multinational studies. Also, multinational studies and abstracts with United States nationality were more frequently presented in oral and poster fashion and had more frequent involvement of the pharmaceutical industry. CONCLUSION: This study provides a geographic overview of clinical cancer research and indicates that multinational collaboration is increasing.

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

The pattern of iron deficiency with and without anemia among medical college girl students in high altitude southern Saudi Arabia.

INTRODUCTION: The prevalence of iron deficiency, latent and symptomatic, is heterogeneous worldwide. In this study, we aim to explore the prevalence of iron deficiency, with and without anemia, among medical college females at the high Altitude Aseer region of Southwestern Saudi Arabia. METHODOLOGY: 200 female medical students were randomly sampled, between the ages of 19 and 27 years. Blood samples were collected for complete blood count (CBC) values and serum ferritin determination. Questionnaires were completed in order to collect demographics, medical history, and socioeconomic information of the participants. RESULTS: Prevalence of overall iron deficiency was high (63%, serum ferritin <20 µg/L, 52.5%, ferritin <15 µg/L). Anemia, adjusted for high altitude (defined as less than 13 g/dL was present in 41 participants (20.5%) and 12 (6.5%) have Hb <12 g/dL. Iron-deficiency anemia (Hb <13 g/dL and serum ferritin <15 µg/L) was present in 35 (17.5%). Personal and family history of anemia and poor animal product containing meals were positively correlated with the presence of iron deficiency state. Neither symptoms of anemia, nor the presence of menorrhagia correlate with the presence of iron deficiency anemia. CONCLUSION: Iron deficiency with and without anemia is a very common and condition in young females' population at high altitude. Implementing a lab method to screen for anemia on vulnerable populations is needed. Frequently asymptomatic, the primary care providers should maintain a high degree of suspicion in order to initiate screening for iron status.

Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely defined.

BACKGROUND: The growing availability of active agents makes the development of novel therapies increasingly complex and the choice of end points critical. We assessed the frequency of use of efficacy end points in advanced breast cancer. METHODS: We searched PubMed for randomized trials published between 2000 and 2007 in 10 leading medical journals. We abstracted data on progression-free survival (PFS), time to tumor progression (TTP), response rate (RR) and overall survival. RESULTS: A total of 58 studies enrolled 23,371 assessable patients in 122 treatment arms. The primary end points most frequently used were RR and TTP (n=21 each), followed by PFS (n=14). In five of the trials using TTP as the primary end point, no definition of TTP was reported; in 13 of the other 16 cases, death was counted as an event, making TTP indistinguishable from PFS. Trials having PFS, TTP or time to treatment failure as the primary end point (n=36) had a higher mean number of patients than those using RR (P=0.061). CONCLUSION: Investigators seem to be frequently using PFS and TTP interchangeably in advanced breast cancer. Such use of terms may lead to confusion when results of different trials are compared, and uniform use of definitions seems in order.

Utilization of nano-cryptomelane for the removal of cobalt, cesium and lead ions from multicomponent system: Kinetic and equilibrium studies.

Nano-cryptomelane was prepared and characterized using SEM with mapping, HRTEM, FT-IR spectra, thermal analysis and surface area. The diameter distribution of nano-cryptomelane was found to be 4-6 nm. Sorption performance of the prepared material was studied for the removal of Co2+, Cs+ and Pb2+ from a multi-system solution of equal molar ratio, 1:1:1. The sorption capacity of nano-cryptomelane was found to be 179.6, 442.6 and 716.9 mg/g for Co2+, Cs+ and Pb2+, respectively. The kinetic studies revealed that the sorption process obeys non-linear pseudo-second-order model and is controlled by an intra-particle diffusion mechanism. The equilibrium isotherm investigations outlined that the extended Langmuir isotherm model fits the data reasonably well and it is more applicable than Freundlich multicomponent sorption isotherm. The value of diffusion coefficient for the three metal ions is in the order 10-17 m2/s which indicates the chemisorption nature of the process. The desorption percentage attains the maximum value (98.13%, 97.29 and 97.04 for lead, cesium and cobalt ions, respectively) using 0.7 mol/L of HNO3. This revealed that nano-cryptomelane can be regenerated and reused for farther sorption of Pb2+, Cs+ and Co2+ from wastewater.

Smear Microscopy for Diagnosis of Pulmonary Tuberculosis in Eastern Sudan.

BACKGROUND: In Sudan, tuberculosis diagnosis largely relies on clinical symptoms and smear microscopy as in many other low- and middle-income countries. The aim of this study was to investigate the positive predictive value of a positive sputum smear in patients investigated for pulmonary tuberculosis in Eastern Sudan. METHODS: Two sputum samples from patients presenting with symptoms suggestive of tuberculosis were investigated using direct Ziehl-Neelsen (ZN) staining and light microscopy between June to October 2014 and January to July 2016. If one of the samples was smear positive, both samples were pooled, stored at -20°C, and sent to the National Reference Laboratory (NRL), Germany. Following decontamination, samples underwent repeat microscopy and culture. Culture negative/contaminated samples were investigated using polymerase chain reaction (PCR). RESULTS: A total of 383 samples were investigated. Repeat microscopy categorized 123 (32.1%) as negative, among which 31 were culture positive. This increased to 80 when PCR and culture results were considered together. A total of 196 samples were culture positive, of which 171 (87.3%), 14 (7.1%), and 11 (5.6%) were M. tuberculosis, M. intracellulare, and mixed species. Overall, 15.6% (57/365) of the samples had no evidence of M. tuberculosis, resulting in a positive predictive value of 84.4%. CONCLUSIONS: There was a discordance between the results of smear microscopy performed at local laboratories in the Sudan and at the NRL, Germany; besides, a considerable number of samples had no evidence of M. tuberculosis. Improved quality control for smear microscopy and more specific diagnostics are crucial to avoid possible overtreatment.

Modulation of the antioxidant defence in different developmental stages of Schistosoma mansoni by praziquantel and artemether.

Human schistosomiasis is a chronic and debilitating parasitic disease caused by parasitic trematode worms (schistosomes). Praziquantel (PZQ) is the drug of choice as it is active against all Schistosoma species, can be administered easily, has high cure and egg reduction rates, with no or only mild side effects. Rapid re-infection following treatment and the concerns about PZQ resistance has led to the search for new drugs to treat schistosomiasis. Significant progress has been made with artemisinin derivatives (e.g., artemether [ART]) that are used for chemoprophylaxis. This present study aims to look at the effects of ART and PZQ on the antioxidant defence of immature (three-week-old) and mature (six-week-old) stages of S. mansoni. The possible development of time- or concentration-dependent changes in oxidative stress is assessed by incubation with different sublethal drug concentrations (50, 75, 100 ng/mL for both ART and PZQ) and different time periods (one and three hours). The results indicated a time- and concentration-dependent depletion of glutathione (GSH), which was greater in the immature worms after incubation with ART. On addition of ART to the incubation medium of mature and immature worms, elevation in lipid peroxidation (TBARS) level was observed, which was time- and concentration-dependent, and more prominent in the immature schistosomes. Addition of PZQ to the incubation medium containing the immature schistosomes did not have a significant effect on TBARS level, except after three hours' incubation with the highest concentration used; however, a significant rise was seen in the mature worms. The PZQ had no effect on the activities of superoxide dismutase (SOD), glutathione peroxidase (tGPx, sGPx and nGPx) and glutathione transferase (GST) in mature or immature worms. While ART induced SOD activity in mature worms, it induced tGPx, nGPx and GST activities in a time- and concentration-dependent manner in both mature and immature worms. Activation was more prominent in the immature schistosomes. The results of the present study indicate that the immature schistosomes are more prone to oxidative killing, which probably participates in the mechanism of antischistosomal action of ART against the immature stage of S. mansoni. The results suggest that the mechanism of schistosomicidal action of PZQ is probably not substantially dependent on oxidative stress or oxidative killing.