Thalidomide as salvage therapy for VAD-refractory multiple myeloma prior to autologous PBSCT

Several trials have shown the activity of thalidomide (THAL) in relapsed multiple myeloma (MM) patients failing PBSCT or conventional chemotherapy. PBSCT is considered standard treatment for most patients requiring therapy for MM; however, patients with VAD-resistant disease may not be able to receive PBSCT due to rapidly advancing disease. We report four cases of VAD-refractory MM salvaged with THAL + VAD followed by PBSCT. All patients underwent stem cell mobilization with cyclophosphamide (Cy) (4.5 g/m(2)) and GMCSF. Melphalan (140-200 mg/m(2)) was given as conditioning. All patients engrafted within 12-16 days after PBSCT. Day +100 evaluation showed the following: very good partial response (n = 1) and complete response (n = 3). After a median follow-up to 153 days, two patients continue to take THAL with no signs of disease progression. One patient developed CHF and was taken off THAL while another patient has died of progressive disease while on THAL (MTD 50 mg). In conclusion, VAD-refractory patients were salvaged with the addition of THAL to VAD. They were subsequently able to undergo autologous PBSCT for MM, which will likely improve their overall survival. This suggests that THAL and other related immunomodulatory drugs may prove useful for initial MM therapy in combination with standard chemotherapy followed by PBSCT.     

A fatty acid desaturase modulates the activation of defense signaling pathways in plants

Salicylic acid (SA) plays an important role in activating various plant defense responses, including expression of the pathogenesis-related (PR) genes and systemic acquired resistance. A critical positive regulator of the SA signaling pathway in Arabidopsis is encoded by the NPR1 gene. However, there is growing evidence that NPR1-independent pathways can also activate PR expression and disease resistance. To elucidate the components associated with NPR1-independent defense signaling, we isolated a suppressor of the npr1-5 allele, designated ssi2. The recessive ssi2 mutation confers constitutive PR gene expression, spontaneous lesion formation, and enhanced resistance to Peronospora parasitica. In contrast, a subset of defense responses regulated by the jasmonic acid (JA) signaling pathway, including expression of the defensin gene PDF1.2 and resistance to Botrytis cinerea, is impaired in ssi2 plants. With the use of a map-based approach, the SSI2 gene was cloned and shown to encode a stearoyl-ACP desaturase (S-ACP DES). S-ACP DES is an archetypical member of a family of soluble fatty acid (FA) desaturases; these enzymes play an important role in regulating the overall level of desaturated FAs in the cell. The activity of mutant S-ACP DES enzyme was reduced 10-fold, resulting in elevation of the 18:0 FA content in ssi2 plants. Because reduced S-ACP DES activity leads to the induction of certain defense responses and the inhibition of others, we propose that a FA-derived signal modulates crosstalk between different defense signaling pathways.     

The lamina push test: an alternative to the globe push test for identifying the medial orbit during endoscopic sinus surgery

Background

Aside from endoscopic and image guidance confirmation, the standard method of identifying the lamina involves the surgeon or an assistant applying gentle pressure on the globe externally. This globe push test requires the surgeon to remove one instrument from the endoscopic field or an assistant to press on the globe, and the test is most useful when either the periorbita or periorbital fat is exposed. We propose an alternative, equally accurate, and more efficient technique dubbed the lamina push test.

Methods

A blunt instrument is used to gently apply lateral pressure in the expected location of the medial orbital wall. If the lamina has been adequately skeletonized, the entire lamina will be seen to move as a unit. If residual ethmoid partitions are present, no movement or only localized movement is observed.

Results

Using the lamina push test, we have been able to safely identify the lamina papyracea in all patients undergoing endoscopic sinus surgery, without injury to the lamina or orbital contents. The use of direct pressure significantly increases the movement of an intact lamina.

Conclusion

The lamina push test is a safe and effective technique for identification of the medial orbital wall, confirmation of removal of all lateral ethmoid partitions, and verification of lamina integrity. It enables more consistent identification of an intact lamina, allows the surgeon to keep both instruments in the endonasal surgical field, and does not require an assistant.

     

Assessing Diagnostic Accuracy of Haemoglobin Colour Scale in Real-life Setting

The study was undertaken to determine diagnostic accuracy of Haemoglobin Colour Scale (HCS) in hands of village-based community health workers (CHWs) in real-life community setting in India. Participants (501 women) were randomly selected from 8 villages belonging to a project area of SEWA-Rural, a voluntary organization located in India. After receiving a brief training, CHWs and a research assistant obtained haemoglobin readings using HCS and HemoCue^TM (reference) respectively. Sensitivity, specificity, positive and negative predictive-values, and likelihood ratios were calculated. Bland-Altman plot was constructed. Mean haemoglobin value, using HCS and HemoCue^TM were 11.02 g/dL (CI 10.9-11.2) and 11.07 g/dL (CI 10.9-11.2) respectively. Mean difference between haemoglobin readings was 0.95 g/dL. Sensitivity of HCS was 0.74 (CI 0.65-0.81) and 0.84 (CI 0.8-0.87) whereas specificity was 0.84 (CI:0.51-0.98) and 0.99 (CI:0.97-0.99) using haemoglobin cutoff limits of 10 g/dL and 7 g/dL respectively. CHWs can accurately diagnose severe and moderately-severe anaemia by using HCS in real-life field condition after a brief training.Key words: Anaemia, Community health worker, Haemoglobin Colour Scale, Sensitivity, Specificity     

Integrity of medial temporal structures may predict better improvement of spatial neglect with prism adaptation treatment

Prism adaptation treatment (PAT) is a promising rehabilitative method for functional recovery in persons with spatial neglect. Previous research suggests that PAT improves motor-intentional “aiming” deficits that frequently occur with frontal lesions. To test whether presence of frontal lesions predicted better improvement of spatial neglect after PAT, the current study evaluated neglect-specific improvement in functional activities (assessment with the Catherine Bergego Scale) over time in 21 right-brain-damaged stroke survivors with left-sided spatial neglect. The results demonstrated that neglect patients’ functional activities improved after two weeks of PAT and continued improving for four weeks. Such functional improvement did not occur equally in all of the participants: Neglect patients with lesions involving the frontal cortex (n?=?13) experienced significantly better functional improvement than did those without frontal lesions (n?=?8). More importantly, voxel-based lesion-behavior mapping (VLBM) revealed that in comparison to the group of patients without frontal lesions, the frontal-lesioned neglect patients had intact regions in the medial temporal areas, the superior temporal areas, and the inferior longitudinal fasciculus. The medial cortical and subcortical areas in the temporal lobe were especially distinguished in the “frontal lesion” group. The findings suggest that the integrity of medial temporal structures may play an important role in supporting functional improvement after PAT.     

Contribution of Endogenous Glucagon-Like Peptide 1 to Glucose Metabolism After Roux-en-Y Gastric Bypass

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕ_Total, 13 ± 1 vs. 11 ± 1 × 10⁻⁹ min⁻¹_, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.     

Outcome of percutaneous continuous drainage of psoas abscess: A clinically guided technique

Background:

Percutaneous aspiration of abscesses under ultrasonography (USG) and computer tomography (CT) scan has been well described. With recurrence rate reported as high as 66%. The open drainage and percutaneous continuous drainage (PCD) has reduced the recurrence rate. The disadvantage of PCD under CT is radiation hazard and problems of asepsis. Hence a technique of clinically guided percutaneous continuous drainage of the psoas abscess without real-time imaging overcomes these problems. We describe clinically guided PCD of psoas abscess and its outcome.

Materials and Methods:

Twenty-nine patients with dorsolumbar spondylodiscitis without gross neural deficit with psoas abscess of size >5 cm were selected for PCD. It was done as a day care procedure under local anesthesia. Sequentially, aspiration followed by guide pin-guided trocar and catheter insertion was done without image guidance. Culture sensitivity was done and chemotherapy initiated and catheter kept till the drainage was <10 ml for 48 hours. Outcome assessment was done with relief of pain, successful abscess drainage and ODI (Oswestry Disability Index) score at 2 years.

Results:

PCD was successful in all cases. Back and radicular pain improved in all cases. Average procedure time was 24.30 minutes, drain output was 234.40 ml, and the drainage duration was 7.90 days. One patient required surgical stabilisation due to progression of the spondylodiscitis resulting in instability inspite of successful drainage of abscess. Problems with the procedure were noticed in six patients. Multiple attempts (n = 2), persistent discharge (n = 1) for 2 weeks, blocked catheter (n = 2) and catheter pull out (n = 1) occurred with no effect on the outcome. The average ODI score improved from 62.47 to 5.51 at 2 years.

Conclusions:

Clinically guided PCD is an efficient, safe and easy procedure in drainage of psoas abscess.     

Tracheotomy after laryngotracheopasty: Risk factors over 10 years

Background

Subglottic stenosis (SGS) is the most common congenital and/or acquired laryngotracheal anomaly requiring tracheotomy in infants. We sought to determine factors associated with a greater likelihood of tracheotomy in symptomatic infants with SGS who underwent laryngotracheoplasty (LTP).

Methods

Retrospective case series with chart review of patients undergoing single-stage LTP for SGS over a 10-year period (2001–2010) in a tertiary-care pediatric hospital.

Results

Twenty-two children (15 boys, 7 girls), with a mean gestational age of 32.5 weeks, underwent LTP with and without interpositional grafting, at a median age of 89 days. Ten patients (43%) required postoperative tracheotomy. Of patients weighing < 2.5 kg, 7 of 8 eventually required tracheotomy, while none weighing > 5 kg needed tracheotomy (p = 0.003). The average length of stay for patients with a tracheotomy was 125 days, while those without tracheotomy required only 58 days (p = 0.011). The grade of SGS (p = 0.809), gender (p = 0.968), age at surgery (p = 0.178), and gestational age (p = 0.117) were not significantly associated with the need for tracheotomy. Weight at surgery was significantly correlated with the likelihood of needing tracheotomy (p = 0.003).

Conclusions

Patients who weighed less than 2.5 kg at the time of LTP procedures were more likely to require a postoperative tracheotomy. Children who required tracheotomy had longer lengths of hospital stay.