The concentration of platelets in PRP does not affect pain outcomes in lateral epicondylitis: a systematic review and meta-analysis.

Aim: To investigate the analyze the relationship between concentration platelet-dose in platelet-rich plasma (PRP) injections and improvements in pain when treating lateral epicondylitis. Methods: A systematic review was conducted into five medical databases, exploring the difference in pain outcomes based on concentration of PRP. Results: Initial querying of the databases yielded 1408 articles with 20 articles ultimately included. There was no statistical significance between effect sizes of the two treatment groups (high and low platelet concentration; p = 0.976). Conclusion: Both large and small concentrations of platelets depict significant reduction in pain, however, between subgroups there was no significance. It can thus be concluded that concentration of platelets in PRP does not impact overall pain relief.

[Box: see text].

Return to Sports After Closed Reduction of Acute Traumatic Posterior Sternoclavicular Joint Dislocations: A Systematic Review.

BACKGROUND: Acute traumatic posterior sternoclavicular (SC) joint dislocation is a serious injury given its potential to cause cardiovascular and airway compromise that typically will require emergent closed reduction. There are limited data on the rate of return to sports (RTS) after this injury pattern when treated in a closed fashion. PURPOSE: To systematically review the literature and evaluate (1) the rate of RTS after closed reduction of posterior SC dislocation and (2) the timeline for RTS after closed reduction of posterior SC dislocation. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed using the PubMed, EBSCOhost, and Elsevier databases with the search term "sternoclavicular dislocation." Inclusion criteria were publications reporting successful closed reduction of posterior SC joint dislocation and containing data relevant to the study objectives. Exclusion criteria were cases with unsuccessful closed reduction, open surgical reduction, concomitant fracture, epiphyseal disruption, superior or anterior dislocation, subluxation injury, treatment without reduction, and atraumatic or congenital origins. RESULTS: Sixteen studies and an additional forthcoming case at the authors' institution were identified to have documented RTS with a total of 31 patients. Of these patients, 23 (74%) in the cohort had full RTS. Eight of the 16 studies plus the additional case reported a timeline for RTS. The mean time to RTS was 3.1 months (range, 1-6 months). Of the 8 patients who did not return to preinjury sports or activity, 12.9% (4/31) reported restrictions with sports or activity, 6.5% (2/31) changed to a sport with less contact, 3.2% (1/31) experienced symptomatic recurrence requiring surgical stabilization, and 3.2% (1/31) quit the sport. CONCLUSION: Closed reduction of acute traumatic posterior SC joint dislocations provides high RTS rates with low rates of secondary surgical stabilization. The mean time to RTS at the preinjury activity level was 3.1 months.

Biobank for multidrug-resistant tuberculosis research: importance of sequential samples.

Since 2013, Masan National Tuberculosis Hospital has collected standardized specimens from its tuberculosis patients, which include a large number of multidrug-resistant strains. The repository collects matched participants and their bacilli samples, compiling sequential samples from the beginning of treatment. The repository aims to provide resources for in-depth international research.

Scalable Synthesis of Hollow ß-SiC/Si Anodes via Selective Thermal Oxidation for Lithium-Ion Batteries.

Silicon for anodes in lithium-ion batteries has received much attention owing to its superior specific capacity. There has been a rapid increase of research related to void engineering to address the silicon failure mechanism stemming from the massive volume change during (dis)charging in the past decade. Nevertheless, conventional synthetic methods require complex synthetic procedures and toxic reagents to form a void space, so they have an obvious limitation to reach practical application. Here, we introduce SiCx consisting of nanocrystallite Si embedded in the inactive matrix of ß-SiC to fabricate various types of void structures using thermal etching with a scalable one-pot CVD method. The structural features of SiCx make the carbonaceous template possible to be etched selectively without Si oxidation at high temperature with an air atmosphere. Furthermore, bottom-up gas phase synthesis of SiCx ensures atomically identical structural features (e.g., homogeneously distributed Si and ß-SiC) regardless of different types of sacrificial templates. For these reasons, various types of SiCx hollow structures having shells, tubes, and sheets can be synthesized by simply employing different morphologies of the carbon template. As a result, the morphological effect of different hollow structures can be deeply investigated as well as the free volume effect originating from void engineering from both a electrochemical and computational point of view. In terms of selective thermal oxidation, the SiCx hollow shell achieves a much higher initial Coulombic efficiency (>89%) than that of the Si hollow shell (65%) because of its nonoxidative property originating from structural characteristics of SiCx during thermal etching. Moreover, the findings based on the clearly observed different electrochemical features between half-cell and full-cell configuration give insight into further Si anode research.

Influence of Surface Charges/Chemistry on the Catalysis of Perovskite Complexes.

The electrochemical performance of the perovskite complex was discovered to depend greatly on the different locations of the identical particle, which represent different surface charges accordingly. The surface charges were evaluated by Zeta potential (ζ) for the intrinsic BSCF5582 (Ba0.5Sr0.5Co0.8Fe0.2O3 -δ), ball-milled (BM-BSCF5582), and heat-treated in an oxygen atmosphere after ball-milling (48h-O2-BM-BSCF5582), the mean ζ of which represents -11.1, 21.2, and -6.1 mV, respectively, which reflects well on different surface chemistries. When the bonding structures at the different stratified layers and the overall crystalline morphologies were analyzed via X-ray photoelectron spectroscopy and high resolution transmission electron microscopy, respectively, the crystalline- and bonding-structure at the 50 nm depth of BSCF5582 is nearly identical to that of BM-BSCF5582 at the surface. As ball-milling proceeds, not only are particles comminuted but also the amorphous surface is broken open, leading to the revelation of inner and naïve cubic crystalline phase surfaces and affecting the catalytic activities of oxygen evolution reactions and oxygen reduction reactions positively and negatively, respectively, at significant scales.

Drifts in ADCC-related quality attributes of Herceptin®: Impact on development of a trastuzumab biosimilar.

A biosimilar product needs to demonstrate biosimilarity to the originator reference product, and the quality profile of the latter should be monitored throughout the period of the biosimilar's development to match the quality attributes of the 2 products that relate to efficacy and safety. For the development of a biosimilar version of trastuzumab, the reference product, Herceptin®, was extensively characterized for the main physicochemical and biologic properties by standard or state-of-the-art analytical methods, using multiple lots expiring between March 2015 and December 2019. For lots with expiry dates up to July 2018, a high degree of consistency was observed for all the tested properties. However, among the lots expiring in August 2018 or later, a downward drift was observed in %afucose (G0+G1+G2). Furthermore, the upward drift of %high mannose (M5+M6) was observed in the lots with expiry dates from June 2019 to December 2019. As a result, the combination of %afucose and %high mannose showed 2 marked drifts in the lots with expiry dates from August 2018 to December 2019, which was supported by the similar trend of biologic data, such as FcγRIIIa binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity. Considering that ADCC is one of the clinically relevant mechanisms of action for trastuzumab, the levels of %afucose and %high mannose should be tightly monitored as critical quality attributes for biosimilar development of trastuzumab.

Physicochemical and biological characterization of SB2, a biosimilar of Remicade® (infliximab).

A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor-α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy.

Scabies Among Elderly Korean Patients with Histories of Leprosy.

A scabies epidemic, traced by the hospital-based surveillance system, was reported in a Korean leprosarium. A total of 200 symptomatic cases were found during 2012-2014 among 570 elderly former leprosy patients. Most of cases were classic type scabies (87%) and aged 75 years and older (72%). Surveillance system for early diagnosis and prompt intervention was applied and the scabies epidemic was controlled effectively in this long-term care facility.

Preparation of Core-Shell Hybrid Compounds by Atomic Transfer Radical Polymerization and Its Application to Plastic Lens of Headlamp.

Nano silica ball (NSB) core polymethylmethacrylate (PMMA) shell hybrid nanocomposites were synthesized by atomic transfer radical polymerization (ATRP) method for the application to the clearcoat to enhance scratch resistance. The characteristics of the synthesized inorganic/organic hybrid material were examined by scanning electron microscope (SEM), particle size analysis, Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis-differential scanning calorimetry (TGA-DSC). The scratch resistance and light transmittance of the clearcoat were measured by a nano-scratch tester and UV-visible spectroscopy, respectively. The average particle size of the NSB-PMMA hybrid compounds was 30 nm with narrow size distribution. Even 0.1 wt% loading of NSB-PMMA in the clearcoat dramatically enhanced the scratch resistance, about 40% increase in the force of the first fracture, while slightly reduced the light transmittance, about 5% only.

Effects of high voltage pulsed current stimulation with a visible contraction intensity on expression of TGF-ß1 and synthesis of type I collagen in wound-induced white rats.

[Purpose] This study aimed to examine the expression of transforming growth factor ß1 (TGF-ß1) and type I collagen by applying high voltage pulsed current stimulation (HVPCS) with a visible contraction intensity to white rats with induced wounds. [Subjects] Thirty-six white rats were used for this study. HVPCS with a non-visible contraction intensity was applied to experimental group I, and HVPCS with a visible contraction intensity was applied to experimental group II. Placebo stimulation was applied to the control group. [Methods] After wounds were triggered, the intervention appropriate for each group was applied. Changes in the size of their wounds and expression of TGF- ß1 and type I collagen were measured on the third, fifth, and seventh days. [Results] Comparison of the sizes of the wounds among the groups showed that the most significant decreases were found in experimental group II on the fifth and seventh days. TGF-ß1 expression comparison revealed that experimental group II had the most expression on the fifth day. [Conclusion] HVPCS with a visible contraction intensity was effective in promoting wound healing by increasing expression of TGF-ß1 and synthesis of type I collagen.

PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.

Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.

Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

Impact of diabetes on treatment outcomes and long-term survival in multidrug-resistant tuberculosis.

BACKGROUND: Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). OBJECTIVES: We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. METHODS: MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. RESULTS: Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). CONCLUSIONS: Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death.

Linezolid for treatment of chronic extensively drug-resistant tuberculosis.

BACKGROUND: Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS: We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS: By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS: Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.

Delamanid for multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).

Changes in cell-mediated immune response after lung resection surgery for MDR-TB patients.

The immune responses of multidrug-resistant tuberculosis (MDR-TB) patients undergoing lung resection surgery were investigated in order to understand the mechanism of strong immune suppression in MDR-TB. We examined changes in cell-mediated immune response (CMI) of a total of sixteen MDR-TB patients, three of them extensively drug-resistant tuberculosis (XDR-TB) patients, after the removal of the heavily diseased lung section. The IFN-γ response to Mycobacterium tuberculosis culture filtrate proteins (Mtb-CFP), one of the most important CMI to defend TB, showed a statistically significant elevation in 2-4 months after operation when compared to the preoperative CMI in patients who were converted into AFB negative and cured in two years' follow-up, suggesting that the recovery of CMI may be one of the key factors in the successful treatment of MDR-TB. Interestingly, IL-10 response to Mtb-CFP was also elevated in 2-4 months after surgery in cured patients although both proliferative response and PBMC composition were not significantly changed. Infection with first- or second-line drugs resistant Mtb reduces the efficiency of chemotherapeutic treatment of MDR-TB to about 50%. Thus, this study suggests that chemotherapeutic treatment of MDR-TB may be more effective when combined with accompanying therapy that increases CMI, includes lung resection surgery.

Enantiomer self-disproportionation and chiral stationary phase based selective chiral separation of organic compounds.

In modern chromatography, chiral stationary phase (CSP) and enantiomer self-disproportionation (ESD) are new inventions of packing material offer a guarantee for a successful enantiomeric separation. All CSPs were synthesized by chemical bonding of the relevant organic moieties onto a porous parent silica material for the separation of various racemic mixtures whereas achiral silica matrix was used for separation of non-racemic mixtures in ESD. Our present study provides to establish an understanding on the entire enantio-selective profile of amino alcohol based CSP as well as ESD and their precise utilization for high success rates for selective enantiomer separation with its appropriateness.

Treatment outcomes and survival based on drug resistance patterns in multidrug-resistant tuberculosis.

RATIONALE: Few large-scale studies have investigated multidrug-resistant tuberculosis (MDR-TB) treatment outcomes relative to drug-resistance patterns. OBJECTIVES: To assess the impact of additional drug resistances on treatment outcomes and long-term survival in a large HIV-negative MDR-TB cohort. METHODS: Treatment outcomes and long-term survival of patients with MDR-TB newly diagnosed or retreated in 2000 to 2002 were retrospectively analyzed based on drug-resistance patterns after 5-8 years of follow-up. MEASUREMENTS AND MAIN RESULTS: Of 1,407 patients with MDR-TB, 75 (5.3%) had extensively drug-resistant TB (XDR-TB(re)) by the revised definition; 159 (11.3%) had ofloxacin-resistant pre-XDR-TB (pre-XDR-TB(o)); and 117 (8.3%) had second-line injectable drug (SLID)-resistant pre-XDR-TB (pre-XDR-TB(s)). Patients with XDR-TB(re) showed the lowest treatment success rate (29.3%) and the poorest long-term survival, and XDR-TB(re) was more strongly associated with long-term mortality than XDR-TB as originally defined (hazards ratio [HR], 3.15; 95% confidence interval [CI], 2.06-4.83; P < 0.001 vs. HR, 2.15; 95% CI, 1.49-3.09; P < 0.001). Patients with either form of pre-XDR-TB showed poorer cumulative survival than those with ofloxacin-susceptible/SLID-susceptible MDR-TB (P < 0.05 for each comparison). Although streptomycin susceptibility did not affect the treatment outcomes of patients with pre-XDR-TB, streptomycin-resistant pre-XDR-TB was more strongly associated with long-term mortality than ofloxacin-susceptible/SLID-susceptible MDR-TB (HR, 2.17; 95% CI, 1.22-3.84; P < 0.008 for pre-XDR-TB(o); and HR, 2.69; 95% CI, 1.40-5.16; P = 0.003 for pre-XDR-TB(s)). CONCLUSIONS: The revised XDR-TB definition is appropriate for defining patients with MDR-TB with the poorest outcomes. Both pre-XDR-TB(o) and pre-XDR-TB(s) were independently associated with poor long-term survival in patients with MDR-TB. SM susceptibility was linked to better survival in patients with pre-XDR-TB.