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Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients with advanced melanoma but is not limited to melanoma patients. Many patients are refractory to TIL-ACT, however, or their cancer becomes resistant. Combining anti-programmed cell death protein 1 (anti-PD-1) with TIL-ACT to antagonize the immunosuppressive tumor microenvironment may synergize to enhance the antitumor potential., Material and Methods: We set up the BaseTIL trial (NCT04165967), a single-center investigator-initiated phase I trial, to test feasibility and safety of TIL-ACT followed by PD-1 blockade in patients with advanced cutaneous melanoma with disease progression after at least one line of anti-PD-1. TIL-ACT included tumor collection, ex vivo TIL expansion, lymphodepletion with cyclophosphamide and fludarabine, TIL transfer, and in vivo TIL stimulation with interleukin 2 (125 000 IU/kg, 10 days). TIL-ACT was followed by nivolumab treatment for a maximum of 2 years. Nine patients were planned for inclusion., Results: Between 2020 and 2022, we enrolled 11 patients and 9 underwent a TIL transfer (median transfused cell number: 66.25 × 10 9 ). Two patients did not start lymphodepletion. Nine patients received at least 1 dose of interleukin 2 (median number: 10; range, 1-10), seven started nivolumab (median number: 5; range, 2-23). All patients had hematologic adverse events (AEs). Most common non-hematologic AEs were fever and cytokine release syndrome. No nivolumab-associated AEs of ≥ grade 2 occurred. The objective response rate to TIL-ACT was 22% (2/9, 2 partial remission)., Conclusions: TIL-ACT with nivolumab is feasible and safe. Larger trials are needed to further determine the efficacy of this combination., (© 2024 The Author(s).)

Patients with acute coronary syndrome (ACS) have a high risk of subsequent adverse cardiovascular outcomes, particularly within the first 30 days. Although it is well documented that initiation of statin therapy in the setting of ACS improves short- and long-term cardiovascular outcomes, and achievement of lower levels of low density lipoprotein cholesterol (LDL-C) incrementally improves outcomes, many patients with ACS have persistent hypercholesterolemia after discharge from the hospital. This is a missed opportunity that prompted the Lipid Association of India to develop recommendations for earlier initiation of more aggressive LDL-C lowering treatment, particularly for patients of South Asian descent who are well-documented to have earlier onset of more aggressive atherosclerotic cardiovascular disease. The Lipid Association of India recommends individualized aggressive LDL-C goals after ACS, which can be rapidly achieved with high intensity statin therapy and subsequent goal-directed adjunctive treatment with ezetimibe and PCSK9 inhibitors. Improved treatment of hypercholesterolemia achieved within weeks after ACS has the potential to reduce the high rate of morbidity and mortality in these high risk patients., (Copyright © 2022. Published by Elsevier Inc.)

Mycoplasma hominis is a common colonizer of the lower genitourinary tract. Although its clinical relevance for causing urogenital infections in immunocompetent individuals is controversial, this bacterium has been involved in severe invasive infections in allograft recipients. In this report, we describe two cases of M. hominis infection in two young renal transplant recipients within the first month post-transplant. Although at first no epidemiological link between the two cases had been suspected, whole-genome sequencing (WGS) analysis showed that both isolates were identical, highly suggestive of an origin with the common organ donor.

Background: Infection is the second highest cause of mortality in end-stage renal disease, with a significant proportion relating to haemodialysis (HD) vascular access-related infection (VARI)., Aim: To report the rate and antimicrobial resistance (AMR) of all-source bloodstream infections (BSIs) by vascular access type in a Scottish HD cohort., Methods: Retrospective analysis was undertaken of data on adult patients attending seven HD units during 2017. Total HD days for each vascular access type were calculated. BSIs were analysed with rates expressed per 1000 HD days. AMR was verified using health board microbiology databases., Findings: Excluding contaminant organisms, there was an overall BSI rate of 0.57 per 1000 HD days. The highest all-source and vascular access-related infection (VARI) BSI rates per 1000 HD days were in the non-tunnelled central venous catheter (CVC) group (3.11 and 2.07 respectively), followed by tunnelled CVC (1.10 and 0.67), arteriovenous graft (0.51 and 0.31), and finally arteriovenous fistula (0.29 and 0.02). The non-VARI BSI rates were lowest in the arteriovenous graft group. Staphylococci comprised the majority of events, with Staphylococcus aureus implicated in 29%. Gram-negative BSIs were prevalent, particularly in CVC groups, and associated with higher mortality. Multidrug-resistant (MDR) S. aureus and carbapenem resistance were relatively low. MDR Gram-negatives were high compared with the Scottish population., Conclusion: Arteriovenous fistula access is confirmed as having lowest all-source and VARI BSI rates, and arteriovenous graft access the lowest non-VARI BSI rates. Staphylococci remain the prevailing genus; however, the contributions of Gram-negative BSIs, the higher mortality, and proportion of MDR organisms in this group are notable., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

A 61-year old lady with poorly-controlled type 2 diabetes mellitus was diagnosed with rhino-orbital-cerebral mucormycosis following presentation with sinusitis, ophthalmoplegia, proptosis and facial numbness. She was treated successfully with aggressive surgical intervention including orbital exenteration, accompanied by anti-fungal therapy with liposomal amphotericin B and posaconazole, followed by isavuconazole as salvage therapy. We discuss the challenges around optimising antifungal therapy of this lethal infection in the context of hepatic and renal toxicity., Competing Interests: There are none., (© 2021 The Authors. Published by Elsevier B.V. on behalf of International Society for Human and Animal Mycology.)

Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15-77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.

Purpose: Our aim was to develop a high-quality, mobile cone-beam computed tomography (CBCT) scanner for point-of-care detection and monitoring of low-contrast, soft-tissue abnormalities in the head/brain, such as acute intracranial hemorrhage (ICH). This work presents an integrated framework of hardware and algorithmic advances for improving soft-tissue contrast resolution and evaluation of its technical performance with human subjects., Methods: Four configurations of a CBCT scanner prototype were designed and implemented to investigate key aspects of hardware (including system geometry, antiscatter grid, bowtie filter) and technique protocols. An integrated software pipeline (c.f., a serial cascade of algorithms) was developed for artifact correction (image lag, glare, beam hardening and x-ray scatter), motion compensation, and three-dimensional image (3D) reconstruction [penalized weighted least squares (PWLS), with a hardware-specific statistical noise model]. The PWLS method was extended in this work to accommodate multiple, independently moving regions with different resolution (to address both motion compensation and image truncation). Imaging performance was evaluated quantitatively and qualitatively with 41 human subjects in the neurosciences critical care unit (NCCU) at our institution., Results: The progression of four scanner configurations exhibited systematic improvement in the quality of raw data by variations in system geometry (source-detector distance), antiscatter grid, and bowtie filter. Quantitative assessment of CBCT images in 41 subjects demonstrated: ~70% reduction in image nonuniformity with artifact correction methods (lag, glare, beam hardening, and scatter); ~40% reduction in motion-induced streak artifacts via the multi-motion compensation method; and ~15% improvement in soft-tissue contrast-to-noise ratio (CNR) for PWLS compared to filtered backprojection (FBP) at matched resolution. Each of these components was important to improve contrast resolution for point-of-care cranial imaging., Conclusions: This work presents the first application of a high-quality, point-of-care CBCT system for imaging of the head/ brain in a neurological critical care setting. Hardware configuration iterations and an integrated software pipeline for artifacts correction and PWLS reconstruction mitigated artifacts and noise to achieve image quality that could be valuable for point-of-care detection and monitoring of a variety of intracranial abnormalities, including ICH and hydrocephalus., (© 2020 American Association of Physicists in Medicine.)

Competing Interests: Declaration of competing interest Dr. Pinkerton reports non-financial support from Pfizer, grants from Therapeutics MD, non-financial support from Amag, outside the submitted work; none in past 12 months. Drs. Sinno, Febbraro, Jones, Khanna, Temkin, Iglesias and Pothuri report no conflict of interest. All authors contributed equally to this practice statement.

A World Health Organization (WHO) Feb 2018 report has recently shown that mortality rate due to brain or central nervous system (CNS) cancer is the highest in the Asian continent. It is of critical importance that cancer be detected earlier so that many of these lives can be saved. Cancer grading is an important aspect for targeted therapy. As cancer diagnosis is highly invasive, time consuming and expensive, there is an immediate requirement to develop a non-invasive, cost-effective and efficient tools for brain cancer characterization and grade estimation. Brain scans using magnetic resonance imaging (MRI), computed tomography (CT), as well as other imaging modalities, are fast and safer methods for tumor detection. In this paper, we tried to summarize the pathophysiology of brain cancer, imaging modalities of brain cancer and automatic computer assisted methods for brain cancer characterization in a machine and deep learning paradigm. Another objective of this paper is to find the current issues in existing engineering methods and also project a future paradigm. Further, we have highlighted the relationship between brain cancer and other brain disorders like stroke, Alzheimer's, Parkinson's, and Wilson's disease, leukoriaosis, and other neurological disorders in the context of machine learning and the deep learning paradigm.

Background: To reduce the risk of transmission of meticillin-resistant Staphylococcus aureus (MRSA), international guidelines recommend admission screening to identify hospital patients at risk of colonization. However, routine monitoring indicates that optimum screening compliance levels are not always achieved. In order to enhance compliance, we must better understand those factors which influence staff screening behaviours., Aim: To identify factors which influence staff compliance with hospital MRSA screening policies., Methods: A sequential two-stage mixed-methods design applied constructs from normalization process theory and the theoretical domains framework to guide data collection and analysis. Initial qualitative findings informed subsequent development of a national cross-sectional survey of nursing staff (N = 450). Multiple regression modelling identified which barriers and enablers best predict staff compliance., Findings: Three factors were significant in predicting optimum (>90%) compliance with MRSA screening: having MRSA screening routinized within the admission process; category of clinical area; feedback of MRSA screening compliance within the clinical area. Integration of data-sets indicated that organizational systems which 'make doing the right thing easy' influence compliance, as does local ward culture. Embedded values and beliefs regarding the relative (de)prioritization of MRSA screening are important., Conclusion: To our knowledge, this is the first study to provide original evidence of barriers and enablers to MRSA screening, applying both sociological and psychological theory. As antimicrobial resistance is a global health concern, these findings have international relevance for screening programmes. Future policy recommendations or behaviour change interventions, based on the insights presented here, could have significant impact upon improving screening compliance., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Echinocandins represent the first-line treatment of candidaemia. Acquired echinocandin resistance is mainly observed among Candida albicans and Candida glabrata and is associated with FKS hotspot mutations. The commercial Sensititre YeastOne™ (SYO) kit is widely used for antifungal susceptibility testing, but interpretive clinical breakpoints are not well defined. We determined echinocandins epidemiological cut-off values (ECV) for C. albicans/glabrata tested by SYO and assessed their ability to identify FKS mutants in a national survey of candidaemia., Methods: Bloodstream isolates of C. albicans and C. glabrata were collected in 25 Swiss hospitals from 2004 to 2013 and tested by SYO. FKS hotspot sequencing was performed for isolates with an MIC≥ECV for any echinocandin., Results: In all, 1277 C. albicans and 347 C. glabrata were included. ECV 97.5% of caspofungin, anidulafungin and micafungin were 0.12, 0.06 and 0.03 μg/mL for C. albicans, and 0.25, 0.12 and 0.03 μg/mL for C. glabrata, respectively. FKS hotspot sequencing was performed for 70 isolates. No mutation was found in the 52 'limit wild-type' isolates (MIC=ECV for at least one echinocandin). Among the 18 'non-wild-type' isolates (MIC>ECV for at least one echinocandin), FKS mutations were recovered in the only two isolates with MIC>ECV for all three echinocandins, but not in those exhibiting a 'non-wild-type' phenotype for only one or two echinocandins., Conclusion: This 10-year nationwide survey showed that the rate of echinocandin resistance among C. albicans and C. glabrata remains low in Switzerland despite increased echinocandin use. SYO-ECV could discriminate FKS mutants from wild-type isolates tested by SYO in this population., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: There is lack of recent multicenter epidemiological data on invasive aspergillosis (IA) among solid organ transplant recipient (SOTr) in the mold-acting antifungal era. We describe the epidemiology and outcomes of IA in a contemporary cohort of SOTr using the Swiss Transplant Cohort Study., Methods: All consecutive SOTr with proven or probable IA between 01.05.2008 and 31.12.2014 were included. A case-control study to identify IA predictors was performed: 1-case was matched with 3-controls based on SOT type, transplant center, and time post-SOT., Results: Among 2868 SOTr, 70 (2.4%) patients were diagnosed with proven (N: 30/70, 42.9%) or probable (N: 40/70, 57.1%) IA. The incidence of IA was 8.3%, 7.1%, 2.6%, 1.3%, and 1.2% in lung, heart, combined, kidney, and liver transplant recipients, respectively, Galactomannan immunoassay was positive in 1/3 of patients tested. Only 33/63 (52.4%) of patients presented with typical pulmonary radiographic findings. Predictors of IA included: renal insufficiency, re-operation, and bacterial and viral infections. 12-week mortality was higher in liver (85.7%, 6/7) compared to other (15.9%, 10/63; P < .001) SOTr., Conclusions: Invasive aspergillosis remains a rare complication post-SOT, with atypical radiographic presentations and low positivity rates of biomarkers posing significant diagnostic challenges. Although overall mortality has decreased in SOTr, it remains high in liver SOTr., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To report our experience of failure mode and effective analysis for high dose rate brachytherapy of gynaecological cancer carried out in our hospital., Materials and Methods: Failure mode and effective analysis process described in AAPM TG 100 was followed: a multidisciplinary team consisting of two physicians, physicists, dosimetrists, a medical resident, a nurse, and a secretary was formed. A weekly meeting was held for four months. A process tree was created based on the overview of the entire process, with the main branches as follows: procedure in the operating room, patient imaging, contouring, treatment planning, machine quality assurance and treatment delivery. Each team member assigned the risk probability numbers based on the predefined scoring system. For a particular failure mode, if the risk probability number assigned by one member differed from the other, the highest risk probability number was taken into consideration., Results: The process tree consisted of 185 nodes, with risk probability numbers ranging from 1-220, with 77 possible failure modes. Four nodes were found with risk probability numbers greater than 200, which were considered for immediate process improvements. Twenty-four nodes were found to be with risk probability numbers ranging from 100 to 200. All 24 processes were considered for process improvement, out of which 12 were found effective and feasible, which includes failure nodes with high severity score at least 8. The processes with high-risk probability numbers (greater than 200) were reduced after the introduction of process improvements. For the other processes, standard procedures were modified. The common causes of failure, were found to be due to lack of attention, human error and work pressure., Conclusions: Failure mode and effective analysis is a useful tool that uses a systematic approach for quality management of a specific process., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Azathioprine (AZA)-induced pancreatitis is an unpredictable and dose-independent adverse event affecting 2%-7% of patients with inflammatory bowel disease (IBD) patients treated with AZA. There are no tools in clinical practice to identify at-risk individuals; however, a genome wide association study (GWAS) identified a strong association between the Class II HLA gene region polymorphism (rs2647087) and thiopurine-induced pancreatitis., Aim: To independently confirm the findings of the GWAS in an IBD cohort, to evaluate its utility in clinical practice and to offer a novel AZA treatment algorithm for IBD based on pharmacogenomic principles., Methods: A retrospective cohort study evaluated 373 AZA-exposed IBD patients from a tertiary care academic centre in London, Canada. Due to the limited number of patients taking mercaptopurine (MP), such patients were not included this cohort. All subjects underwent screening for the single nucleotide polymorphism (SNP) rs2647087 mapped to the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype and were sub-divided based on the presence (n = 13) or absence (n = 360) of an AZA-induced pancreatitis diagnosis. The risk of AZA-induced pancreatitis was assessed based on rs2647087 genotype., Results: The risk of pancreatitis during AZA-therapy was highly predictable and genotype dependent: 0.53% for wild type (A/A), 4.25% (OR = 4.19, 95% CI 1.02-36.45, P = 0.044) for heterozygous (A/C), and 14.63% (OR = 15.83, 95% CI 3.80-145.26, P = 0.0001) for homozygous variant (C/C) patients., Conclusions: The class II HLA region (at rs2647087) is an important marker of AZA-induced pancreatitis risk. We propose a simple and clinically implementable algorithm based on rs2647087 and TPMT genotypes for AZA selection and dosing for patients with IBD., (© 2017 John Wiley & Sons Ltd.)

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aims: To review various pathologic parameters in diagnosed cases of trunk and extremity-based soft tissue tumors (STTs), in order to identify concordance rate between initial biopsy and resection specimen and discrepancies between initial and review diagnosis, by a specialist pathologist., Materials and Methods: Over a 2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including referral and "in-house" cases were studied. The reviewing specialist pathologist was blinded to the initial diagnoses. Discordances including discrepancies and deficiencies were defined as major and minor. Major discrepancies included those that could lead to significant treatment changes. True discrepancies were those related to sampling issues between the biopsies and resection specimens. Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor size, and marginal status (in resections) were subdivided as major and minor., Results: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma) and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs, liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were relatively more frequently associated with discrepancies. Percentage of cases with major discordances between the referral reports (100 cases) and review diagnosis was 60%. Percentage of cases with major discordances between the specialist and other oncopathologists was 11%. True discrepancies were observed in 20 (5%) cases. The association of type of specimen with the rate of discordance was not significant (P = 0.114)., Conclusions: Diagnoses of STTs are fraught with errors mostly from general pathologists, followed by nonspecialist oncopathologists. These findings reinforce the need for reporting of STTs, especially sarcomas, by specialist pathologists., Competing Interests: There are no conflicts of interest.

Initially used in the treatment of prostate cancer and uterine fibroids, the role of focused ultrasound has expanded as transcranial acoustic wave distortion and other limitations have been overcome. Its utility relies on focal energy deposition via acoustic wave propagation. The duty cycle and intensity of focused ultrasound influence the rate of energy deposition and result in unique physiologic and biomechanical effects. Thermal ablation via high-intensity continuous exposure generates coagulative necrosis of tissues. High-intensity, pulsed application reduces temporally averaged energy deposition, resulting in mechanical effects, including reversible, localized BBB disruption, which enhances neurotherapeutic agent delivery. While the precise mechanisms remain unclear, low-intensity, pulsed exposures can influence neuronal activity with preservation of cytoarchitecture. Its noninvasive nature, high-resolution, radiation-free features allow focused ultrasound to compare favorably with other modalities. We discuss the physical characteristics of focused ultrasound devices, the biophysical mechanisms at the tissue level, and current and emerging applications., (© 2017 by American Journal of Neuroradiology.)

Background: Clear cell carcinoma of cervix (CCCC) is a rare cervical neoplasm that is usually associated with diethylstilbestrol (DES) exposure in utero as a primary risk factor. Advanced stage disease typically has poor outcomes and no evidence-based approach exists to guide clinicians in treating this rare disease., Case: The authors report a case of locally advanced CCCC in a 37-year-old Caucasian female. She underwent chemoradiation therapy that included 109 courses of paclitaxel chemotherapy until no disease could be detected on imaging studies. She is now disease-free 13 years after discontinuing chemotherapy., Conclusion: A prolonged course of single agent paclitaxel after completing standard radiation therapy was successful in achieving remission in a patient with this rare disease.

Purpose of Investigation: Because of rarity, consensus on adjuvant therapies for Type II endometrial cancers (BC) remains undefined. Reporting their institutional outcomes, the present authors assessed the impact of adjuvant therapies on recurrence and overall survival in women with 2009 FIGO Stage I-III Type II BC., Material and Methods: The authors identified 108 women, treated with definitive surgery between 2000-2013, with pathologically-confirmed Type II EC (non-endometrioid [NEM, n=801 and high grade endometrioid [G3EEC, n=28]) Cox proportional hazard models were used to assess the effect of prognostic variables on disease-free (DFS) and overall survival (OS). Kaplan-Meier method was used to assess survival., Results: Of the 108 women, 83 (77%) were African American (AA). Fifty-nine (55%), 12 (11%), and 37 (34%) were Stage I, II, and III, respectively. Ninety-seven patients received adjuvant therapy: 52 (radiation only), four (chemotherapy only), and 40 (combined). During follow-up (median 41 months), 44 patients (41%) recurred. Five-year DFS was 53% overall (48% [NEM], 80% [G3EEC]). Five-year OS was 75% overall (68% [NEM], 95% [G3EEC]). On multivariate analysis, lower stage and adjuvant radiation improved DFS. Higher stage, NEM, and increasing age were poor prognostic indicators of OS., Conclusion: Representing a large single institutional cohort for Type II BC, the present study's observed sur- vival rates are consistent with previous studies, despite the relatively high frequency of carcinosarcoma and Stage III/nodal disease. The protective effect on recurrence was not lost when radiation was delayed for chemotherapy. The present results support a multimodal adjuvant approach for treating all stages of invasive NEM EC.

Background: Azathioprine is a potent immunosuppressive drug that has been used in many immune-mediated diseases. There are a few reports of its use in psoriasis; however, azathioprine weekly pulse doses have not been evaluated in this disease., Aim: The objective of this study was to evaluate the therapeutic effectiveness of weekly oral pulse doses of azathioprine for the treatment of chronic plaque psoriasis, and to determine the side effects of this regimen both clinically and biochemically., Methods: In this open-label clinical trial, a 300 mg bolus dose of azathioprine was given once every week orally for 24 weeks to patients with chronic plaque psoriasis having body surface area involvement of ≥ 10% and Psoriasis Area and Severity Index (PASI) of ≥ 10. Patients were evaluated every 4 weeks for 24 weeks to determine the response to treatment and any adverse effects (AEs), and then followed up for a further period of 12 weeks to determine any relapse of the disease., Results: There were 50 patients in the study, of whom 28 (56%) completed the 24 weeks of treatment and 27 (54%) completed the 12-week post-treatment follow-up. Azathioprine 300 mg weekly pulse was effective in achieving PASI 75 in 42% of patients, PASI 90 in 36% of patients and PASI 100 in 22% of patients. In five patients (10%), the therapy had to be withdrawn due to AEs., Conclusion: Weekly azathioprine pulse appears to be an effective treatment for chronic plaque psoriasis, and can be used as an alternative therapy to other available therapeutic agents., (© 2016 British Association of Dermatologists.)

Ewing sarcoma (ES) of the jaw bones comprises a small fraction of ES at all sites. Due to their rarity, a specific policy for local treatment is lacking. The aim of this study was to evaluate the local therapy for ES and recommend measures to individualize treatment options. Patients with primary non-metastatic ES of the jaw bones treated between August 2005 and February 2015 were analyzed. All patients received primary induction chemotherapy, following which lesions amenable to resection based on specific radiological criteria were resected; those with unresectable lesions were offered definitive radiotherapy. The maxilla was the primary site in 13 patients and the mandible in eight. The median age of patients was 11.6 years (range 5-17 years). Overall, surgery was performed in 17 patients and definitive radiotherapy was used in four patients. Postoperative radiotherapy was administered to 12 patients and was avoided in five patients with 100% tumour necrosis. The 3-year overall survival, event-free survival, and local control were 68.1%, 63.6%, and 80.2%, respectively. Mandible primary and a histological response to chemotherapy were significant prognostic factors. The stratification of patients based on radiological criteria aids in selecting local therapy. In eligible patients, surgery with contemporary reconstruction results in optimal oncological and functional outcomes. Surgery also has the added advantage of identifying patients who may not need radiotherapy., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients exposed to bronchoscopes contaminated with Pseudomonas aeruginosa are at increased risk of pseudomonal infection. The optimal methods for management and mitigation of risk following exposure are controversial. This article describes a two-phase risk assessment following pseudomonal contamination of a family of 75 endoscopes, detected through routine surveillance and attributed to one endoscope washer-disinfector. An initial risk assessment identified 18 endoscopes as high risk, based on the presence of lumens used for irrigation or biopsy. Exposure was communicated to the patients' clinical teams and a further clinical risk assessment of the exposed patients was performed. No patients developed complications due to pseudomonal infection., (Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Syk, an immune regulatory tyrosine kinase, plays a role in inflammatory disease processes. We recently reported a role for epithelial expression of Syk in the airways hyper-responsiveness in response to air pollution in a mouse model of asthma. The aim of this study was to further investigate the role of Syk in airway contractility in response to methacholine (MCh) and particulate matter (PM) air pollutants, in the absence of underlying inflammation., Methods: We used Syk(flox/flox) //rosa26CreER(T) (2) conditional Syk knockout mice to evaluate respiratory mechanics and MCh responsiveness following PM exposure in vivo using the ventilator-based flexiVent system., Results: While total and differential cell counts in bronchoalveolar lavage fluid were similar between the Syk(flox/flox) and Syk(del/del) mice, central airways respiratory resistance (RN ) to MCh was significantly augmented following PM exposure between Syk-intact (Syk(flox/flox) ) and Syk-deficient (Syk(del/del) ) mice (RN (max) : 2.06 ± 0.29 vs. 1.29 ± 0.10, respectively; p < 0.05, n = 8-10/group). We employed live videomicroscopy to investigate changes in airway luminal diameter using ex vivo lung slices, which were devoid of circulating leukocytes. MCh reduced the airway luminal area of Syk(flox/flox) mice to 81.1 ± 1.4% of baseline, which was virtually abrogated in Syk(del/del) mice (luminal area = 93.2 ± 0.5%, n = 5/group, p < 0.05). In response to PM exposure, Syk(flox/flox) airways contracted to 73.8 ± 2.7% of baseline luminal diameter, whereas Syk(del/del) airways exhibited minimal contractility to PM and MCh (90.0 ± 1.3% of baseline, n = 5/group, p < 0.05)., Conclusions: These observations suggest that Syk mediates airway contractility in the normal and allergic airways, independent of its role and function in leukocytes, and supports a paracrine role for airway epithelial Syk in modulating airway smooth muscle activity., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Leprosy stands tall among the oldest and most misunderstood diseases of man. Today leprosy is easily treated; unfortunately, persistent misconceptions result in unnecessary stigmatization. Thus the present study aims to assess the knowledge and attitudes regarding leprosy in people with and without leprosy, factors affecting the same; and to study their relationship with treatment status in leprosy patients. Detailed knowledge and attitude questionnaires were administered to 260 subjects (100 leprosy patients, 60 family members of leprosy patients and 100 people with non-leprosy skin diseases) at AIIMS, New Delhi. Crude scores based on subject responses were used for inter-group comparisons. Leprosy patients had significantly higher knowledge scores than family members who in turn scored significantly higher than people with other skin diseases. Leprosy patients had fair knowledge about common symptoms, but awareness about MDT was low. Delayed diagnosis and non-compliance were common. Attitudes did not differ between groups. Fear of the leprosy-affected and reluctance for physical contact, food sharing and marriage were prominent. Treated leprosy patients had the highest knowledge scores. Higher education and greater knowledge scores were positive predictors of attitude. Knowledge and attitude scores showed significant positive correlation. Knowledge and attitude towards leprosy are unsatisfactory. Improving knowledge may help to improve attitudes. In the post-elimination era, we must incorporate education about the disease into routine care of leprosy patients and focus on community education about leprosy.

Background: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence., Methods: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome., Results: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events., Conclusions: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There is a health crisis in the US related to diet that is further exacerbated by our aging population and sedentary lifestyles. Six of the ten leading causes of death in the United States can be directly linked to diet. Dietary assessment, the process of determining what someone eats during the course of a day, is essential for understanding the link between diet and health. We are developing imaging based tools to automatically obtain accurate estimates of what foods a user consumes. Accurate food segmentation is essential for identifying food items and estimating food portion sizes. In this paper, we present a quantitative evaluation of automatic image segmentation methods for food image analysis used for dietary assessment. The experiments indicate that local variation is more suitable for food image segmentation in general dietary assessment studies where the food images acquired have complex background.

We report on 4 patients with different types of tularemia acquired in Switzerland or nearby countries. All patients presented with fever, moderate to highly elevated signs of inflammation, and local lymphadenopathy. Additionally, 3 patients did not respond to empirical antimicrobial therapy with aminopenicillins. A tick bite was identified as mode of transmission in 2 patients, while 1 patient showed a possible connection to a tick bite. The route of transmission for the fourth patient remained unknown. The diagnosis of tularemia was either based on positive serology, on a positive polymerase chain reaction (PCR) from the lymph node samples or on positive blood cultures. The treatment in adult patients was ciprofloxacin 500-750 mg twice daily orally for 3 weeks. The pediatric patient was treated with gentamicin 4 mg/kg i.v. once daily for 1 week and ciprofloxacin 15 mg/kg twice daily orally for another 2 weeks. All patients recovered completely. Due to the increasing incidence of tularemia in Switzerland, this infection should be considered in patients with fever and lymph node enlargement particularly after tick bite. We recommend treatment with ciprofloxacin orally for 14-12 days.

This article reports on a 38-year-old kidney transplant patient who presented with fever, coughing and dypnea. The patient was immunosuppressed with mycophenolate and prednisone. Due to the suspicion of community acquired pneumonia antibiotic treatment was initiated and the patient was admitted to the intensive care unit. Despite antibiotic treatment the condition did not improve and in the subsequently performed bronchioalveolar lavage parainfluenza virus was diagnosed.Infections with respiratory viruses can be fatal in immunosuppressed patients. Human parainfluenza virus is the third most common pathogen of viral pneumonia. Molecular genetic detection methods allow fast and sensitive diagnosis of respiratory materials. As the treatment options are limited for these infections prophylactic measurements are important.

Background: The clinical characteristics of human metapneumovirus (hMPV)-associated lower respiratory tract infection (LRTI) after allogeneic hematopoietic stem cell transplantation (HSCT) is not well described. We describe the clinical course in eight HSCT recipients suffering from hMPV infection., Methods: We prospectively included all patients with hMPV-associated LRTI after allogeneic HSCT during a period of 1 year. hMPV was diagnosed by multiplex polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL)., Results: Eight patients with hMPV-associated LRTI were identified from 93 BAL samples. Three of the eight patients had co-infections with other pathogens. The median age of the patients was 45 years [interquartile range (IQR) 36.8-53.5], the median time posttransplant was 473 days (IQR 251-1,165), 5/8 patients had chronic graft-versus-host disease (cGvHD), and 6/8 patients received immunosuppression. Chest computed tomography (CT) scanning showed a ground-glass pattern in 7/8 patients. Seven of eight patients required hospitalization due to severe symptoms and hypoxemia. All were treated with intravenous immunoglobulin (IVIG), which was combined with oral ribavirin in six patients. The mortality rate was 12.5 % (1/8)., Conclusions: hMPV-associated LRTI in allogeneic HSCT recipients are not uncommon and present with unspecific respiratory symptoms, ground-glass pattern in CT scanning, and co-infection.

We present a case of Legionella pneumophila serogroup 3 (LP3) infection in a patient with severe community-acquired pneumonia (CAP). The diagnosis was complicated by an initial equivocal L. pneumophila urinary antigen test, followed by two negative samples. LP3 was cultured from a sputum sample and the diagnosis was confirmed by serology 15 days into the admission. This case highlights the importance of considering non-LP1 serogroups as causes of CAP and the role of serological testing in diagnosis.

Traditional dietary assessment methods, consisting of written and orally reported methods, are not widely acceptable or feasible for everyday monitoring. The development of builtin cameras for mobile devices provides a new way of collecting dietary information by acquiring images of foods and beverages. The ability of image analysis techniques to automatically segment and identify food items from food images becomes imperative. Food images, usually consisting of plates, bowls and glasses, are often affected by lighting and specular highlights which present difficulties for image analysis. In this paper, we propose a novel single-image specular highlight removal method to detect and remove specular highlights in food images. We use independent components analysis (ICA) to separate the specular and diffuse components from the original image using only one image. This paper describes the details of the proposed model and also presents experimental results on food images to demonstrate the effectiveness of our approach.

The present study aims to investigate the influence of electrical stimulation of periaqueductal gray (PAG) following peripheral nerve injury and its modulation by naloxone and N-methyl-D-aspartate (NMDA). Chronic neuropathic pain was induced by chronic constriction injury of the sciatic nerve, and subsequently a cannula was implanted in the PAG area for the purpose of electrical stimulation and intra-PAG drug administration. Intra-PAG administration of morphine, ketamine, and their combination were found to elicit antinociceptive response on hot-plate test. Electrical stimulation of PAG was also observed to demonstrate decreased pain response on hot-plate test, and this effect was reversed by the administration of naloxone, NMDA, and their combination, when injected into the PAG area. These findings suggest that apart from the opioid receptors, probably NMDA receptors also have a role to play in stimulation-produced analgesia.

Injecting drug users are prone to atypical infections. We present a case of septic thrombophlebitis secondary to Fusobacterium gonidiaformans infection in a heroin user, which demonstrates the frequently unusual nature of pathogens and presentations in this group of patients.

Objective: Tobacco use and depression are highly prevalent among methadone maintenance (MM) treatment programme participants. Our aim was to study the relationship between nicotine dependence, depression, and readiness to change smoking behaviour among women smokers in MM compared to women smokers attending a primary care clinic (Control group)., Method: We conducted a cross-sectional survey of 117 MM women smokers and 50 controls attending a family medicine clinic. All participants completed a computerized self-administered questionnaire, including demographic information, medical history, and drug and tobacco use history. Participants also completed the Fagerström Test for Nicotine Dependence (FTND), the Center for Epidemiologic Studies Depression Scale (CES-D), and the University of Rhode Island Change Assessment (URICA) instrument., Results: In this study 83% African American women had an average age of 43 years. Of the women smokers in the MM group, 95% were daily smokers compared to 46% in the Control group (P <0.05). The MM women smokers had CES-D scores of 22.5 compared to 14.7 in women of the Control group (P <0.0001). Women smokers in MM were significantly more likely to be depressed, more dependent on nicotine, and more ready to change their smoking behaviour., Conclusions: Our data show a higher level of nicotine dependence and depression, and greater readiness to change among women smokers in methadone maintenance programmes compared to women smokers attending primary care clinics. Methadone treatment programmes present a need and an opportunity to assess and intervene in nicotine dependence and depression and in addressing and eliminating health disparities.

Objective: The study was performed to assess the effect of potassium channel openers on morphine tolerance and vice-versa., Methods: Swiss albino mice of either gender weighing between 25-30 g were used for the study The study assesses the effect of potassium channel openers (cromakalim, diazoxide and minoxidil) on morphine tolerance and vice-versa, using formalin and tail-flick tests., Results: The antinociceptive effect of cromakalim and minoxidil was significantly reduced when administered to morphine-tolerant mice, in both the behavioural tests. However reduced analgesic effect of diazoxide was observed on morphine-tolerance in the formalin test but not in the tail-flick test. Tolerance was observed when morphine was administered to animals chronically treated with any of the potassium channel openers. The same effect was observed when morphine was injected into a group treated with a combination of morphine and any of the potassium channel openers., Conclusions: This study, therefore, suggests that both morphine and potassium channel openers are cross-tolerant. However such interaction occurs at the level of potassium channels rather than at the level of receptors.

Background: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes., Methods: We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV-infected US veterans in the highly active antiretroviral therapy (HAART) era (1996-2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time-dependent variable., Results: A total of 19 424 HIV-infected patients [31.6% of whom were HCV-coinfected (HIV/HCV)] contributed 76 376 patient-years of follow-up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV-only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV-only patients: 4.19 vs. 3.36 events/1000 patient-years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient-years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98-1.61; P=0.072] for AMI and 1.20 (CI 1.04-1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model., Conclusions: In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV-infected patients.

Background: Influenza can cause significant morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). The diagnostic methods and antiviral treatment have scarcely been investigated., Methods: We retrospectively identified influenza-infected patients with upper or lower respiratory tract infection (RTI) diagnosed by culture and polymerase chain reaction (PCR) testing between November 2007 and April 2008. Treatment with oseltamivir 75 mg twice daily and serial nasal swabs were performed at the discretion of the treating physician., Results: We identified 21 influenza infections in 19 patients: 19 with upper RTI and 2 with lower RTI. At diagnosis, all 21 samples were positive for PCR with a median influenza load of 5.9 log(10) copies/mL. Culture was positive in 14 (67%) patients. Influenza A virus was diagnosed in 8 (38%) episodes and influenza B virus in 13 (62%) episodes. Two patients were sequentially infected by influenza A, followed by B after 38 and 47 days, respectively. Eighteen (86%) patients were treated with oseltamivir for 11 days (median, interquartile range [IQR]: 8-14). No progression to lower RTI or mortality occurred. Shedding persisted for 12 days (median, IQR: 8-13). Absolute lymphocyte count at diagnosis correlated inversely with shedding of the virus (P<0.001)., Conclusions: Oseltamivir is well tolerated and may reduce mortality of influenza virus-infected patients after HSCT. PCR may help to optimize diagnosis and to monitor treatment strategies.

Pyogenic liver abscesses are uncommon in clinical practice and are usually polymicrobial in nature, with members of the Enterobacteriacae family often implicated. This report describes the use of tigecycline to treat a liver abscess caused by methicillin-resistant Staphylococcus aureus, which was refractory to therapy with standard antimicrobials.

Aims: To test the hypothesis that compliance with a hospital protocol on peripheral blood culture (PBC) collection in adults is associated with a reduction in PBC contamination, and to investigate likely contributing factors for contamination., Methods: A prospective cohort study was conducted, utilising data collection by participant questionnaire completion, and utilising bacteriology laboratory results on PBCs. Participants were all healthcare workers involved in obtaining PBCs from adults., Results: 1460 PBCs with questionnaires were received. Contamination among the 1460 PBCs as a whole was 8.8%. 766 of the questionnaires were sufficiently complete to allow analysis of blood culture contamination in relation to protocol compliance. Among these, protocol compliance was 30% and contamination was 8.0%. When the protocol was complied with, 2.6% of PBCs were contaminated, but when the protocol was not followed, contamination was significantly higher at 10.3% (OR 4.35, 95% CI 1.84 to 12.54). Univariate analysis on all 1460 PBCs suggested that the site for blood collection, and disinfection of the venepuncture site were important factors in PBC contamination: when no venepuncture site disinfection was performed, contamination was significantly higher than when alcohol was used (5.1% versus 15.8%, OR 3.46, 95% CI 2.01 to 5.97); when a PBC collection site other than a fresh peripheral vein was used, contamination was significantly higher (7.3% versus 12.0%, OR 1.75, 95% CI 1.03 to 2.96)., Conclusions: Compliance with a hospital protocol on PBC collection technique in adults significantly reduces blood culture contamination.

The resurgence of dengue (DEN) virus infections in the last few decades coupled with the lack of a preventive vaccine and specific antiviral drugs has jointly contributed to making this a significant global public health problem. Currently, symptomatic supportive treatment and fluid replacement therapy are the only means available to minimize DEN-induced mortality. As the clinical symptoms associated with DEN virus infections are indistinguishable from those of many other viral, bacterial, and parasitic infections, specific diagnostic tests assume critical importance in the unequivocal identification of DEN virus infections. We have designed a novel chimeric antigen based on envelope domain III (EDIII), a critical antigenic region of the major structural protein of DEN viruses. We fused EDIIIs corresponding to each of the four DEN virus serotypes using pentaglycyl linkers, overexpressed the resultant tetravalent chimeric protein in Escherichia coli, and affinity purified it in high yields, obtaining approximately 30 mg protein of >95% purity per liter of culture. We show that this tetravalent antigen could specifically recognize anti-DEN virus antibodies of both the immunoglobulin M (IgM) and IgG classes. Using a large panel of IgM antibody capture-enzyme-linked immunosorbent assay- and hemagglutination inhibition-confirmed DEN virus-infected and uninfected patient sera (n = 289), we demonstrate that this tetravalent antigen can function as a diagnostic tool of high sensitivity and specificity.

Human papillomavirus (HPV) detection is an integral part of cervical cancer screening, and a range of specimen collection procedures are being tested. Preliminary studies have found that the majority of women prefer self-collection of vaginal specimens instead of clinician-collected specimens of the cervix. The purposes of the current study were to explore the social and behavioral predictors of acceptance of self-collection of vaginal specimens among patients and to assess concordance in detection of HPV between clinician-collected cervical specimens and self-collected vaginal specimens. The study was conducted at a university family medicine clinic using a cross-sectional study design, and enrollment of women presenting for routine gynecological examination consecutively in a period of 1 year, self-administered questionnaires, collection of paired vaginal and cervical specimens for HPV DNA using Hybrid Capture 2, and cytologic analysis. Most women (79.8% [398/499]) agreed to collect vaginal specimens. In our study, 76.6% (216/282) African American women (AA), 88.1% (156/176) white non-Hispanic (WNH) women, and 63.4% (26/41) women of other races (P < 0.0001) agreed to self-collect vaginal specimens. HPV was detected in 16.0% (80/499) of clinician-collected cervical specimens and 26.1% (104/398) of self-collected vaginal specimens (P < 0.001). HPV detection was concordant in 13.4% (53/398) women in both cervical and vaginal specimens. Self-collection of vaginal specimens for HPV DNA detection is acceptable to most women presenting for routine gynecological examination. WNH women were more likely to obtain self-collected specimens than AA women. Vaginal specimens were more likely to be positive for HPV than were cervical specimens.

Unlabelled: Leprosy still remains a public health problem mainly in Asia, Africa and South America. The WHO Expert Committee on Leprosy recommended, in 1997, the simplified treatment of leprosy for multibacillary (MB) cases, by reducing the duration of treatment from 24 to 12 months. From the operational point of view even this reduced duration is still long and monthly supervised drug administration may not always be practical in those areas where the accessibility is difficult and health infrastructure weak. The present study was carried out to compare the safety and efficacy of a new fixed duration regimen consisting of four bactericidal drugs with WHO/MDT (MB)., Methods: Thirty adult patients were randomly allocated to two groups. Group 1 (18 patients) received a new regimen of daily rifampicin 600 mg, sparfloxacin 200 mg, clarithromycin 500 mg and minocycline 100 mg for 12 weeks. Group 2 (12 patients) received WHO/MDT (MB) for 12 months. A detailed clinical evaluation and laboratory investigations, BI and MI were done at the baseline, every 4 weeks for 12 weeks, and thereafter every 8 weeks till 48 weeks. Skin biopsies were taken and chest X-rays were done at 0, 12 and 48 weeks., Results: At 48 weeks, the net percentage clinical improvement in group 1 was 73.92% and in group 2 it was 66.66%. The net percentage reduction (NPR) in BI in group 1 was 19.17% and in group 2 it was 18.87% (p = 0.09). NPR in MI in both groups was 100% by 8 weeks, and somewhat faster in group 1. In group 1, 8 patients had mild gastrointestinal side-effect, and 16 had minocycline-induced hyperpigmentation. Three patients in group 1 developed type I reversal reactions., Conclusion: The regimen containing daily doses of rifampicin 600 mg, sparfloxacin 200 mg, minocycline 100 mg and clarithromycin 500 mg for 12 weeks was found to be an acceptable, effective and safe alternative regimen for MB leprosy with an additional operational advantage of shorter duration of treatment.

Relapse and immune reconstitution syndrome are difficult to distinguish in HIV-infected patients treated with antiretroviral therapy (ART). We report on a 26-year-old HIV-infected male (CDC C3) with hearing loss on the right side 2 months after discontinuing secondary prophylaxis for cryptococcal meningitis. CD4 cell counts had increased from 32/microl to stable counts > 200/microl for the preceding 6 months on ART but HIV replication was not fully suppressed (7,000 copies/ml). Magnetic resonance imaging identified lesions at the origin of the right cranial nerve VIII. Lumbar puncture revealed monocytic pleocytosis, slightly increased protein, but normal glucose and lactate levels, negative microbiological studies. Fluconazole was restarted and a new ART regimen was started in order to fully suppress HIV replication. Clinical and radiological signs were reversible during follow-up, and secondary prophylaxis was stopped after 6 months without adverse events. We review 26 published cases of cryptococcal infections with immune reconstitution syndrome and highlight the distinguishing features.