Linezolid: an effective, safe and cheap drug for patients failing multidrug-resistant tuberculosis treatment in India

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB.     

Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis

Atherosclerosis is characterized by accumulation of lipids and inflammatory cells in the arterial wall. Oxidized low-density lipoprotein (ox-LDL) plays important role in the genesis and progression of atheromatous plaque. Various scavenger receptors have been recognized in the past two decades that mediate uptake of ox-LDL leading to formation of foam cells. Inhibition of scavenger receptor A and CD36 has been shown to affect progression of atherosclerosis by decreasing foam cell formation. Lectin-type oxidized LDL receptor 1 (LOX-1) participates at various steps involved in the pathogenesis of atherosclerosis, and in experimental studies its blockade has been shown to affect the progression of atherosclerosis at multiple levels. In this review, we summarize the role of ox-LDL and scavenger receptors in the formation of atheroma with emphasis on effects of LOX-1 blockade.     

Pulmonary embolectomy with use of pediatric bronchoscope for the detection of residual emboli: an innovative surgical technique

Pulmonary embolectomy in the treatment of massive pulmonary embolus has been in doubt since the introduction of thrombolytic therapy. Recent indications for surgical intervention are- contraindication to thrombolysis, failed medical treatment and severe Right Ventricular (RV) dysfunction. A 54-year male came to us with complaints of palpitation, tachypnea and repeated syncope . Transthoracic echocardiography and Computed Tomography pulmonary angiogram demonstrated- Biatrial mass with right atrial mass extending into right ventricle and main pulmonary artery. Pulmonary embolectomy was performed. Residual emboli of bilateral pulmonary arteries were detected with a fiberoptic pediatric bronchoscope and removed. Bronchoscopic evaluation appears to be safe and useful for direct visual detection of emboli.     

Dsteosynthesis with long volar locking plates for meta- physeal-diaphyseal fractures of the distal radius

Objective：Metaphyseal-diaphyseal fractures of the distal radius are a major treatment dilemma and orthopaedic surgeons have to pay due consideration to restoration of anatomy of distal radius together with rotation of the radial shaft and maintenance of radial bow and interosseous space.We performed this study to evaluate the clinic-radiological outcome of metaphyseal-diaphyseal fractures of the distal radius treated with long volar locking plates.Methods：This prospective study involved 27 patients （22 males and 5 females） with metaphyseal-diaphyseal fracture of the distal radius.Their mean age was （30.12±11.48） years （range 19-52 years） and the follow-up was 26.8 months （range 22-34 months）.All patients underwent open reduction and internal fixation with a long volar locking plate.According to AO/OTA classification,there were 7 type A3,13 type C2 and 7 type C3 fractures.Subjective assessment was done based on the disabilities of the arm,shoulder and hand （DASH） questionnaire.Functional evaluation was done by measuring grip strength and range of motion around the wrist and the radiological determinants included radial angle,radial length,volar angle and ulnar variance.The final assessment was done according to Gartland and Werley scoring system.Results：Postoperative radiological parameters were well maintained throughout the trial,and there was significant improvement in the functional parameters from 6 weeks to final follow-up.The average DASH scores improved from 37.5 at 6 weeks to 4.2 at final follow-up.Final assessment using Gartland and Werley scoring system revealed 66.67%（n=l8） excellent and 33.33% （n=9） good results.There was one case of superficial infection which responded to antibiotics and another carpel tunnel syndrome which was managed conservatively.Conclusion：Volar locking plate fixation for metaphyseal-diaphyseal fractures of distal radius is associated with excellent to good functional outcome,early rehabilitation and minimal complications.     

Proximal humeral reconstruction using nail cement spacer in primary and metastatic tumours of proximal humerus

Limb salvage surgery for malignant tumours of proximal humerus is an operative challenge, where the surgeon has to preserve elbow and hand functions and retain shoulder stability with as much function as possible. We treated 14 consecutive patients with primary malignant or isolated metastasis of proximal humerus with surgical resection and reconstruction by nail cement spacer. There were 8 females and 6 males, with a mean age of 28.92 years (range 16–51 years) and a mean follow-up of 30.14 months (range 12–52 months). The diagnosis was osteosarcoma in 8 patients, chondrosarcoma in 4 patients and metastasis from thyroid and breast carcinoma in 1 patient each. One of our patients had radial nerve neuropraxia, 1 developed inferior subluxation and 3 developed distant metastasis. Two patients died of disease and one developed local recurrence leading to forequarter amputation, leaving a total of 11 patients with functional extremities for assessment at the time of final follow-up which was done using the Musculoskeletal Tumour Society (MSTS) score. Though we were able to preserve the elbow, wrist and hand functions in all patients, the abductor mechanism, deltoid muscle and axillary nerve were not salvageable in any of cases. The mean MSTS score at the time of final follow-up was 19.09. Thus, proximal humeral reconstruction using nail cement spacer is a technical simple, cost-effective and reproducible procedure which makes it a reliable option in subset of patients where the functions around the shoulder cannot be preserved despite costlier prosthesis.     

Subdural evacuating port system (SEPS)—Minimally invasive approach to the management of chronic/subacute subdural hematomas

Objective

The population suffering from chronic/subacute subdural hematomas (SDHs) generally includes elderly patients with co-morbidities; therefore the success of less invasive surgical techniques has been of long standing interest. The optimum treatment option for chronic/subacute SDH has not been well established. We report our retrospective outcomes of SDH drainage through a subdural evacuating port system (SEPS).

Patients and methods

Fifty-two consecutive adult patients with chronic/subacute SDH treated with SEPS (total 64 procedures), over a period of 3 years (June 2006–June 2009), were included. 9/52 patients had SEPS performed for bilateral SDHs. Three patients had SEPS placed for recurrent SDH. This retrospective study was approved by the Institutional Review Board of SUNY Upstate Medical University and Crouse Hospital.

Results

Overall 38/52 patients (73%) showed clinical improvement, 10/52 patients (19%) did not show any clinical improvement and 4/52 (8%) patients became clinically worse after the SEPS placement during initial hospitalization. 41/52 patients, treated initially with SEPS were followed as outpatients. 32/41 patients improved, returning to baseline neurological status, 5/41 patients improved, but still had some residual symptoms. The remaining 4/41 patients, presented with recurrent symptoms and had recurrent SDH on CT scans. During the in-hospital post-SEPS period, 8 SDH had >75% decrease, 17 SDH had between 50 and 75% decrease, 23 SDH had between 25 and 50% decrease and 14 procedures had <25% decrease in maximal width of the SDH on postoperative scans. Outpatient follow up CT scans after SEPS placement were available for 46/64 procedures. At final outpatient follow up, 33/46 SDHs showed >75% decrease in maximal thickness, 4/46 SDH showed between 50 and 75% and 2/46 SDH showed between 25 and 50% decreases in maximal width of chronic SDH. However, in 7/46 patients, SDH re-accumulated (i.e. increased in thickness) as outpatients, after initial response to treatment on post-operative in-hospital CT scans.

Conclusion

SEPS is an effective, relatively safe and convenient treatment strategy with low invasiveness; among management options of chronic/subacute SDH.     

A systematic review of irreversible electroporation in localised prostate cancer treatment

Irreversible electroporation is a treatment option used for focal therapy. In this systematic review, we summarise data on irreversible electroporation outcomes in patients with localised prostate cancer. We performed a literature search in 3 databases and included articles with own data on irreversible electroporation results in patients with localised prostate cancer. Primary outcome was procedure efficacy measured as the absence of cancer in the treatment area on the follow-up biopsy. Secondary outcomes were the absence of prostate cancer recurrence in the treatment area on MRI, out-of-field recurrence, complications and functional outcomes (erectile function and micturition). In-field recurrence rate was 0%–39% and out-field 6.4%–24%. In all studies, PSA level decreased: twice lower than baseline after 4 weeks and by 76% after 2 years. Most of the authors noted sexual and urinary toxicity during the first half year after surgery. However, functional outcomes recovered to baseline after 6 months with mild decrease in sexual function. Complication rates after irreversible electroporation were 0%–1% of Clavien–Dindo III and 5%–20% of Clavien–Dindo I–II. Irreversible electroporation has promise oncological outcomes, rate of post-operative complications and minimal-to-no effects on erectile and urinary function. However, medium and long-term data on cancer-specific and recurrence-free survival are still lacking.     

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BackgroundThe putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent.Questions/purposes(1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma.MethodsIn this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H₂O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation.ResultsConstitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm³ versus 1316 ± 387.4 mm³, mean difference 1009 mm³ [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm³ versus 326.1 ± 72.8 mm³, mean difference 326.1 mm³ [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10⁸ ± 8.3x10⁸ photons/s versus 9.3 x 10⁷ ± 1.5 x 10⁸ photons/s, mean difference 8.6 x 10⁸ photons/s [95% CI 5.1 x 10⁸ to 1.2 x 10⁹]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm³ versus 1335 ± 102.7 mm³, mean difference 840.3 mm³ [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions.ConclusionsAs demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted.Clinical RelevanceOur results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.