B-cell infiltration is associated with survival outcomes following programmed cell death protein 1 inhibition in head and neck squamous cell carcinoma.

BACKGROUND: Programmed cell death protein 1 (PD-1) axis blockade has become the mainstay in the treatment of recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Programmed death-ligand 1 (PD-L1) is the only approved biomarker for patient selection; however, response rate is limited even among high expressors. Our primary objective was to investigate the association of immune cell-related biomarkers in the tumor and tumor microenvironment with PD-1 checkpoint inhibitors' outcomes in patients with R/M HNSCC. PATIENTS AND METHODS: NCT03652142 was a prospective study in nivolumab-treated platinum-refractory R/M HNSCC, aiming to evaluate biomarkers of response to treatment. Tumor biopsies and blood samples were collected from 60 patients at baseline, post-treatment, and at progression. Immune cells in the tumor and stromal compartments were quantified by immunofluorescence using a five-protein panel (CD3, CD8, CD20, FoxP3, cytokeratin). Tertiary lymphoid structures (TLSs), PD-L1 expression, and peripheral blood immune cell composition were also evaluated for associations with outcome. Our findings were validated by gene set enrichment analysis (GSEA) messenger RNA in situ expression data from the same patients, for B-cell- and TLS-associated genes. RESULTS: High pre-treatment density of stromal B cells was associated with prolonged progression-free survival (PFS) (P = 0.011). This result was validated by GSEA, as stromal enrichment with B-cell-associated genes showed association with response to nivolumab. PD-L1 positivity combined with high B-cell counts in stroma defined a subgroup with significantly longer PFS and overall survival (P = 0.013 and P = 0.0028, respectively). CONCLUSIONS: Increased B cells in pre-treatment HNSCC biopsy samples correlate with prolonged benefit from PD-1-based immunotherapy and could further enhance the predictive value of PD-L1 expression.

Long-term treatment of dentine with triple antibiotic paste promotes stem cell viability and attachment.

Objective: Successful regenerative endodontic procedures in dental treatment are critically associated with complete disinfection of the root canal and require irrigants and medicaments. One factor for consideration is the biocompatibility of the medicament as this can affect the intracanal dentine and subsequently the dental stem cell viability required for the repair of the dentine-pulp complex. This in vitro study investigated the effect of a 4-week treatment of calcium hydroxide [Ca(OH)2] and triple antibiotic paste (TAP) on the irrigated radicular dentine by analysing dentine interaction with dental stem cells. Methods: TAP consists of metronidazole, ciprofloxacin and minocycline. Dentine chips were prepared and treated with either Ca(OH)2 or TAP for 4-weeks, irrigated by 1.5% sodium hypochlorite (NaOCl), rinsed with saline, followed by 17% ethylenediaminetetraacetic acid (EDTA). Dental pulp stem cells (DPSCs) cultured on the surface of the dentine chips were analysed on days 1, 3 and 7 of cell seeding for PrestoBlue viability assays, 6-diamidino-2 phenylindole (DAPI) staining and scanning electron microscopy (SEM). An independent t-test (SPSS software version 24.0) was used to statistically analyse the PrestoBlue assay data. Results: DPSCs grown from dentine treated with TAP showed significantly higher cell viability than the Ca(OH)2 and control groups (p < 0.05). DAPI staining of the seeded DPSCs on the treated dental chips complemented the findings of the viability assay. SEM studies also revealed improvements in the cell spreading and attachment of DPSCs grown on TAP-treated dentine compared with Ca(OH)2. Conclusion: The treatment of dentine with TAP for 4 weeks provided a better microenvironment for the viability and attachment of DPSCs when compared to Ca(OH)2.

Uni-vs. bilateral DIEP flap reconstruction - A multicenter outcome analysis.

OBJECTIVE: Over the past decade numbers of bilateral mastectomy have increased steadily. As a result, bilateral breast reconstruction is gaining popularity. The presented study compares complications and outcomes of unilateral and bilateral DIEP free-flap breast reconstructions using the largest database available in Europe. METHODS: Female breast cancer patients (n = 3926) receiving DIEP flap breast reconstructions (n = 4577 free flaps) at 22 different centers were included in this study. Free flaps were stratified into two groups: a unilateral- (UL) and a bilateral- (BL) breast reconstruction group. Groups were compared with regard to surgical complications and free flap outcome. RESULTS: Mean operative time was significantly longer in the BL group (UL: 285.2 ± 107.7 vs. BL: 399.1 ± 136.8 min; p < 0.001). Mean ischemia time was comparable between groups (p = 0.741). There was no significant difference with regard to total (UL 1.8% vs. BL 2.6%, p = 0.081) or partial flap loss (UL 1.2% vs. BL 0.9%, p = 0.45) between both groups. Rates of venous or arterial thrombosis were comparable between both groups (venous: UL 2.9% vs. BL 2.2%, p = 0.189; arterial: UL 1.8% vs. BL 1.2%, p = 0.182). However, significantly higher rates of hematoma at the donor and recipient site were observed in the UL group (donor site: UL 1.1% vs. BL 0.1%, p = 0.001; recipient site UL 3.9% vs. BL 1.7%, p < 0.001). CONCLUSIONS: The data underline the feasibility of bilateral DIEP flap reconstruction, when performed in a setting of specialized centers.

Cross-sectional Study on Assessment of First-pass Success of Video Laryngoscope Intubation in General Anesthesia Patients.

Traditional Direct laryngoscope (DL) has been used by anesthesiologist during intubation for general anesthesia patients for more than a century. Video laryngoscope (VL) helps in better visualization of laryngeal orifice during intubation and reduces intubation time. This was a cross sectional study conducted in two Asian Hospitals Queen Elizabeth II hospital of Kotakinabalu, Malaysia and King Faisal Hospital Taif of Saudi Arabia to assess the first-pass success of video laryngoscope and to compare with direct laryngoscope from July 2015 to December 2017. Random lottery technique was applied for sampling. Participants of both groups (VL and DL) were enrolled by simple lottery method. Total 146 patients were enrolled with a set inclusion criterion. Mallampati class, mouth opening, thyromental distance and mobility of atlantooccipital junction were set as predictors of first-pass success. The first-pass success was 98.7% in mallampati II patients and 92.8% in mallampati III patients. Average success rate was 95.75%. The mean success rate of VL and DL was compared and was found VL had a significantly better first-pass success rate than DL (p<0.05).

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Effect of HBO therapy on adipose-derived stem cells, fibroblasts and co-cultures: In vitro study of oxidative stress, angiogenic potential and production of pro-inflammatory growth factors in co-cultures1.

BACKGROUND: A key moderator of wound healing is oxygen. Wound healing is a dynamic and carefully orchestrated process involving blood cells, cytokines, parenchymal cells (i.e. fibroblasts and mesenchymal stem cells) and extracellular matrix reorganization. Human adipose derived stem cells as well as human fibroblasts produce soluble factors, exhibit diverse effects on inflammation and anti inflammation response and are involved in wound healing processes.Hyperbaric oxygen therapy is an effective adjunct treatment for ischemic disorders such as chronic infection or chronic wounds. In vitro effects of hyperbaric oxygen therapy on human cells were presented in many studies except for those on mono- and co-cultures of human adipose derived stem cells and fibroblasts. OBJECTIVE: The aim of this study was to investigate the effects of hyperbaric oxygen therapy on mono- and co-cultures of human adipose derived stem cells and fibroblasts. METHODS: Mono- and co-cultures from human adipose derived stem cells and fibroblasts were established. These cultures were exposed to hyperbaric oxygen therapy every 24 h for five consecutive days. Measuring experiments were performed on the first, third and fifth day. Therapy effects on the expression of VEGF, IL 6 and reactive oxygen species were investigated. RESULTS: After exposure to hyperbaric oxygen, cell culturess showed a significant increase in the expression of VEGF after 3 and 5 days. All cultures showed significantly reduced formation of reactive oxygen species throughout the experiments. The expression of IL-6 decreased during the experiment in mono-cultures of human adipose derived stem cells and co-cultures. In contrast, mono-cultures of human skin fibroblasts showed an overall significantly increased expression of IL-6. CONCLUSIONS: Hyperbaric oxygen therapy leads to immunmodulatory and proangiogenetic effects in a wound-like enviroment of adipose derived stem cells and fibroblasts.

Serotyping of dengue virus in 2016-17 outbreak in Kudat, Sabah, Malaysia.

An outbreak of dengue in Kudat, northern Sabah in 2016-2017 provided an opportunity to investigate the circulating serotypes of dengue viruses of cases at Hospital Kudat. Between September 2016 and December 2017, a total of 156 dengue positive sera (tested positive by either NS1 antigen, or IgM and IgG antibody rapid test) were collected from dengue patients who had acute fever and showed signs and symptoms suggestive of dengue. RNA was extracted from the sera using QIAamp RNA Blood Mini Kit, and molecular amplification was performed using one-step RT-PCR kit, followed by nested PCR using HotStart Taq master mix kit with the primers of the dengue C-prM gene. There were 81 (52%) male and 75 (48%) female cases. The age group with the highest number of cases was the 10-19 years old, while the youngest infected was 8 months old and the oldest was 83 years old. RT-PCR results showed 88 sera dengue positive, 48 infected with a single serotype while another 40 with multiple serotypes. All four DENV serotypes were co-circulating during the outbreak period and DENV-1 was predominant. Molecular analysis also indicated 69.2%, 50.0%, 51.9% and 48.9% respectively of the NS1, IgM, IgG and IgM and IgG positive sera were RT-PCR positive for dengue. High number of cases were seen in December 2016, February and May 2017. The dengue outbreak might be related to switching of predominant serotype from DENV 4 to DENV 1.

Serotyping of dengue virus in 2016-17 outbreak in Kudat, Sabah, Malaysia

@# An outbreak of dengue in Kudat, northern Sabah in 2016-2017 provided an opportunity to investigate the circulating serotypes of dengue viruses of cases at Hospital Kudat. Between September 2016 and December 2017, a total of 156 dengue positive sera (tested positive by either NS1 antigen, or IgM & IgG antibody rapid test) were collected from dengue patients who had acute fever and showed signs and symptoms suggestive of dengue. RNA was extracted from the sera using QIAamp RNA Blood Mini Kit, and molecular amplification was performed using one-step RT-PCR kit, followed by nested PCR using HotStart Taq master mix kit with the primers of the dengue C-prM gene. There were 81 (52%) male and 75 (48%) female cases. The age group with the highest number of cases was the 10-19 years old, while the youngest infected was 8 months old and the oldest was 83 years old. RT-PCR results showed 88 sera dengue positive, 48 infected with a single serotype while another 40 with multiple serotypes. All four DENV serotypes were co-circulating during the outbreak period and DENV-1 was predominant. Molecular analysis also indicated 69.2%, 50.0%, 51.9% and 48.9% respectively of the NS1, IgM, IgG and IgM & IgG positive sera were RT-PCR positive for dengue. High number of cases were seen in December 2016, February and May 2017. The dengue outbreak might be related to switching of predominant serotype from DENV 4 to DENV 1.

Fractional Deletion of Compound Kushen Injection Indicates Cytokine Signaling Pathways are Critical for its Perturbation of the Cell Cycle.

We used computational and experimental biology approaches to identify candidate mechanisms of action of aTraditional Chinese Medicine, Compound Kushen Injection (CKI), in a breast cancer cell line (MDA-MB-231). Because CKI is a complex mixture of plant secondary metabolites, we used a high-performance liquid chromatography (HPLC) fractionation and reconstitution approach to define chemical fractions required for CKI to induce apoptosis. The initial fractionation separated major from minor compounds, and it showed that major compounds accounted for little of the activity of CKI. Furthermore, removal of no single major compound altered the effect of CKI on cell viability and apoptosis. However, simultaneous removal of two major compounds identified oxymatrine and oxysophocarpine as critical with respect to CKI activity. Transcriptome analysis was used to correlate compound removal with gene expression and phenotype data. Many compounds in CKI are required to trigger apoptosis but significant modulation of its activity is conferred by a small number of compounds. In conclusion, CKI may be typical of many plant based extracts that contain many compounds in that no single compound is responsible for all of the bioactivity of the mixture and that many compounds interact in a complex fashion to influence a network containing many targets.

Augmented reality of indocyanine green fluorescence in simplified lymphovenous anastomosis in lymphatic surgery.

BACKGROUND: A physiological and minimal invasive form of surgery with minimal risk to treat lymphedemas is the so-called supermicrosurgical lymphovenous anastomosis (LVA) where a lymph vessel is connected with a venule. METHODS: 30 patients (between 2018 and 2019) with secondary upper extremity lymphedema refractory to conservative therapy (manual lymph drainage and compression therapy were operated using the "simplified lymphovenous anastomosis" method). For the assessment of lymphatic supermicrosurgery, an operating microscope in which a near-infrared illumination system is integrated (Leica M530 OHX with glow technology ULT530, Leica Microsystems) and the IC-FlowTM Imaging System(Diagnostic Green)/Visionsense System (Medtronic) together with a ZEISS S8 microscope was used. Augmented reality intraoperative indocyanin green (ICG) lymphography-navigated modified "simplified lymphovenous anastomosis" were performed on the Leica microscope. All patients were informed about Off-label-use of ICG lymphography. RESULTS: 57 LVAs were performed with modified "simplified lymphovenous anastomosis" lymphography-guidance on 30 upper extremities. All patients showed good patency after lymphovenous anastomosis. CONCLUSIONS: Supermicrosurgery in the case of LVA is minimally invasive, highly effective, and shows a very low complication rate. The surgeon/equipment-related factors restrict the pratice of LVA, and its effectiveness limited by technical constraints.

Attrition during pre-ART and ART time periods among adolescents enrolled in Integrated HIV Care Programme in Myanmar, 2005-2017.

Retaining adolescents (aged 10-19 years), living with HIV (ALHIV) on antiretroviral therapy (ART) is challenging. In Myanmar, 1269 ALHIV were under an Integrated HIV Care (IHC) Programme by June 2017 and their attrition (death and lost to follow-up) rates were not assessed before. We undertook a cohort study using routinely collected data of ALHIV enrolled into HIV care from July 2005 to June 2017 and assessed their attrition rates in June 2018 by time-to-event analysis. Of 1269 enrolled, 197(16%) and of 1054 initiated ART, 224 (21%) had an attrition defining event. The pre-ART and ART attrition rates were 21.8 (95% CI 19.0-25.1) and 6.4 (95% CI 5.6-7.3) per 100 person-years follow-up, respectively. The factors 'at enrolment' that were associated with higher hazards of attrition were: (1) WHO stage 3 or 4; (2) haemoglobin <10 gm/dl; (3) no documented CD4 cell counts, hepatitis B and C test results; and (4) injection drug use. Baseline hazards were high during the initial 1-2 years and after 5-6 years. The pre-ART and ART attrition rates in ALHIV were lower than those in Africa but higher than the children under IHC. This warrants designing and implementing additional care tailored to the needs of ALHIV under IHC.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

SETTING: Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. OBJECTIVE: To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). DESIGN: A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. RESULTS: Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). CONCLUSION: Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

High prevalence and incidence of tuberculosis in people living with the HIV in Mandalay, Myanmar, 2011-2017.

SETTING: Two human immunodeficiency virus (HIV) clinics providing antiretroviral therapy (ART), Mandalay, Myanmar. OBJECTIVE: To assess prevalent TB at enrolment, incident TB during follow-up and associated risk factors in adult people living with HIV (PLHIV) between 2011 and 2017. DESIGN: Cohort study using secondary data. RESULTS: Of 11 777 PLHIV, 2911 (25%) had prevalent TB at or within 6 weeks of enrolment. Independent risk factors for prevalent TB were being male or single/widowed, daily alcohol consumption, CD4 count 200 cells/µl and anaemia. During 6 years follow-up in 8866 PLHIV with no prevalent TB, the rate of new TB was 2.9 per 100 person-years (95%CI 2.6-3.1). Cumulative TB incidence was 9.6%, with 370 (72%) of 517 new TB cases occurring in the first year. Independent risk factors for incident TB were being male and anaemia. Incident TB was highest in the first year of ART, in PLHIV with CD4 counts 200 cells/µl and those not receiving isoniazid preventive therapy (IPT). Incident TB declined with time on ART and rising CD4 counts. CONCLUSION: Prevalent and incident TB were high in PLHIV in the Mandalay clinics. Consideration should be given to earlier TB diagnosis using more sensitive diagnostic tools, effective ART and scaling up IPT.

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

WITHDRAWN: The use of integrated indocyanine green fluorescence microscope camera for intraoperative lymphography of supermicrosurgery.

Ahead of Print article withdrawn by publisher.

Treatment outcome of tuberculosis patients detected using accelerated vs. passive case finding in Myanmar.

SETTING: Several projects involving accelerated or active case finding (ACF) of tuberculosis (TB) cases are being implemented in Myanmar. However, there is a concern that patients detected using ACF have poorer TB treatment outcomes than those detected using passive case finding (PCF). OBJECTIVE: To assess differences in the demographics, clinical profile and treatment outcomes of patients detected using ACF and PCF. DESIGN: Retrospective cohort study of TB patients diagnosed and enrolled for treatment during 2014-2016. RESULTS: Of 16 048 patients enrolled, 2226 (16%) were detected using ACF; the treatment success rate (cured and completed) was 88%. A higher proportion of cases detected using ACF were aged 55 years, human immunodeficiency virus (HIV) negative and sputum smear-positive pulmonary TB. After adjusting for differences in demographic and clinical characteristics, we found that treatment outcomes in patients detected using ACF and PCF were not significantly different (adjusted relative risk [aRR] 0.89, 95%CI 0.78-1.00). Male sex, age  55 years, patients with a previous history of TB and HIV positivity were independently associated with unsuccessful outcomes. CONCLUSION: ACF detected a significant proportion of TB cases in study townships; treatment outcomes in cases detected using ACF and those detected using PCF were similar. More tailored interventions are needed to improve treatment outcomes in patients at a higher risk of unsuccessful treatment outcomes.

Vascular malformations of upper and lower extremity - from radiological interventional therapy to surgical soft tissue reconstruction - an interdisciplinary treatment.

This article presents our experience in managing peripheral vascular malformations of upper and lower extremities over a 4-year period in a series of 46 patients of the Department of Plastic Surgery treated in the Interdisciplinary Center of Vascular Anomalies (ICVA) at the University of Regensburg. The patients presented vascular malformations of upper and lower extremity and were selected from our prospective vascular anomalies file archive from 2012 to 2016. During this period in the ICVA at University of Regensburg were performed more than 1400 radiological interventional treatments in patients with vascular malformations.The purpose of this retrospective study was to review combined embolotherapy, sclerotherapy (embolo/sclerotherapy), and surgical procedures (surgical excision and soft tissue reconstruction) to manage vascular malformations. Treatments were principally induced to reduce pain, daily physical limitations, social discomfort and recover tegument continuity after ulceration.The 46 patients were first examined with noninvasive radiological procedures. After diagnosis was posed, embolo/sclerotherapy, surgical procedures and clinically as well as radiological follow-ups were coordinated and established by the multidisciplinary team. All vascular malformations were categorized according to the classification approved at the April 2014 General Assembly of International Society for the Study of Vascular Anomalies (ISSVA) in Melbourne, Australia. Arteriovenous malformations (AVMs) were further classified following the Cho-Do and Schobinger classification.Embolo/sclerotherapy shows to be the most appropriate procedure in vascular malformations treatment. Nevertheless was found that in case of complications or lack of improvement as well as to improve functional or aesthetical results, a following partial or complete surgical excision and immediate soft tissue reconstruction seems to be the gold-standard treatment. In addition, the precise clinical and radiological diagnosis as well as an intensive postoperative patient care have a significant positive influence on the clinical outcome and patient satisfaction while decreasing morbidity and recurrence during early and late follow-up.Vascular malformations require a multidisciplinary approach and individual treatment after complex excision and indispensable reconstruction.