Post-discharge mortality in adult patients hospitalized for tuberculosis: a prospective cohort study.

Determining outcomes and predictors of mortality following discharge from tuberculosis (TB) hospitalization is crucial to establish health policies. The objective of this study was to analyze outcomes and, secondarily, predictors of mortality following discharge from TB hospitalization. This was a prospective cohort study of patients diagnosed with TB (all forms) discharged from the hospital who began treatment during hospitalization. Out of 169 subjects included, 38 died during the 13-months of follow-up, within a median of 3 months (95%CI: 1.49-4.51). In the multivariate analysis, the variables independently associated with death were age (HR=1.04, 95%CI: 1.01-1.06, P=0.001), presence of sputum production (HR=2.18, 95%CI: 1.09-4.34, P=0.027), and Charlson Comorbidity Index (HR=1.19, 95%CI: 1.04-1.36, P=0.015). In conclusion, post-discharge mortality in subjects hospitalized for TB was 22.5%, with mean survival of 4.6 months. The mortality was higher in older subjects, in those who reported sputum production, and in those with a high comorbidity index.

Post-discharge mortality in adult patients hospitalized for tuberculosis: a prospective cohort study

Determining outcomes and predictors of mortality following discharge from tuberculosis (TB) hospitalization is crucial to establish health policies. The objective of this study was to analyze outcomes and, secondarily, predictors of mortality following discharge from TB hospitalization. This was a prospective cohort study of patients diagnosed with TB (all forms) discharged from the hospital who began treatment during hospitalization. Out of 169 subjects included, 38 died during the 13-months of follow-up, within a median of 3 months (95%CI: 1.49-4.51). In the multivariate analysis, the variables independently associated with death were age (HR=1.04, 95%CI: 1.01-1.06, P=0.001), presence of sputum production (HR=2.18, 95%CI: 1.09-4.34, P=0.027), and Charlson Comorbidity Index (HR=1.19, 95%CI: 1.04-1.36, P=0.015). In conclusion, post-discharge mortality in subjects hospitalized for TB was 22.5%, with mean survival of 4.6 months. The mortality was higher in older subjects, in those who reported sputum production, and in those with a high comorbidity index.

Analysis of copy number variation in men with non-obstructive azoospermia.

BACKGROUND: Recent findings demonstrate that single nucleotide variants can cause non-obstructive azoospermia (NOA). In contrast, copy number variants (CNVs) were only analysed in few studies in infertile men. Some have reported a higher prevalence of CNVs in infertile versus fertile men. OBJECTIVES: This study aimed to elucidate if CNVs are associated with NOA. MATERIALS AND METHODS: We performed array-based comparative genomic hybridisation (aCGH) in 37 men with meiotic arrest, 194 men with Sertoli cell-only phenotype, and 21 control men. We filtered our data for deletions affecting genes and prioritised the affected genes according to the literature search. Prevalence of CNVs was compared between all groups. Exome data of 2,030 men were screened to detect further genetic variants in prioritised genes. Modelling was performed for the protein encoded by the novel candidate gene TEKT5 and we stained for TEKT5 in human testicular tissue. RESULTS: We determined the cause of infertility in two individuals with homozygous deletions of SYCE1 and in one individual with a heterozygous deletion of SYCE1 combined with a likely pathogenic missense variant on the second allele. We detected heterozygous deletions affecting MLH3, EIF2B2, SLX4, CLPP and TEKT5, in one subject each. CNVs were not detected more frequently in infertile men compared with controls. DISCUSSION: While SYCE1 and MLH3 encode known meiosis-specific proteins, much less is known about the proteins encoded by the other identified candidate genes, warranting further analyses. We were able to identify the cause of infertility in one out of the 231 infertile men by aCGH and in two men by using exome sequencing data. CONCLUSION: As aCGH and exome sequencing are both expensive methods, combining both in a clinical routine is not an effective strategy. Instead, using CNV calling from exome data has recently become more precise, potentially making aCGH dispensable.

Brainstem Dysfunction in Healthy Aging.

The brainstem controls sub-cortical and cortical activity and influences the processing of incoming information. The goal of this study was to characterize age related alterations of brainstem-brain interactions during different brain states detected by dynamic analysis of task-free fMRI. 79 young (20-40 years) and 51 older adults (55-80 years) were studied. Internal brainstem structures were segmented using a new multi-contrast segmentation approach. Brain and brainstem gray matter segmentations were warped onto a population template. The ICV-corrected Jacobian determinants were converted into z-score maps and the means from 420 cortical/subcortical/brainstem rois extracted. The fMRI was preprocessed in SPM12/Conn18 and the BOLD signal from 420 cortical/subcortical/brainstem rois extracted. A dynamic task-free analysis approach based on hierarchical cluster analysis was used to identify 15 brain states that were characterized using graph analysis (strength, diversity, modularity). Kruskal-Wallis tests and Spearman correlations were used for statistical analysis. One brain state (cluster 21) occurred more often in older adults (p=0.008). It was characterized by a lower mean modular strength and brainstem-cortical strength in older adults compared to younger adults. Global age related gray matter differences were positively correlated with brain state 21's modular strength. Furthermore, brain state 21 duration was negatively correlated with working memory (r = -0.28, p=0.002). The findings suggest an age related weakening of the within and between network synchronization at the brainstem level during brain state 21 in older adults that negatively affects cortical and subcortical synchronization and working memory performance.

Preparing healthcare facilities to operate safely and effectively during the COVID-19 pandemic: The missing piece in the puzzle.

The stated objective of the COVID-19 lockdown was to allow time to prepare healthcare facilities. Preparation must include administrative and environmental measures, which when combined with personal protective equipment, minimise the risk of the spread of infection to patients and healthcare workers (HCWs) in facilities, allowing HCWs to safely provide essential services during the pandemic and limit the indirect effects of COVID-19 caused by healthcare disruption. We present our model for facility preparation based on colour-coded zones, social distancing, hand hygiene, rapid triage and separate management of symptomatic patients, and attention to infection transmission prevention between HCWs in communal staff areas. This model specifically addresses the challenges in preparing a facility for COVID-19 in a low-resource setting and in rural areas. In addition, we include links to resources to allow workers in low-resource settings to prepare their facilities adequately.

Interferon alfa-2a maintenance after salvage autologous stem cell transplantation in atypical mycosis fungoides with central nervous system involvement.

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with unfavourable prognosis for patients with advanced stages of the disease. Refractory disease and advanced-stage disease require systemic therapy. We report on a rare case of an atypical predominantly CD8+ folliculotropic MF, a subtype of MF with poorer prognosis, in a 59-year-old woman. She was initially diagnosed with MF restricted to the skin, of T3N0M0B0/stage IIB according to the current World Health Organization-European Organisation for Research and Treatment of Cancer classification. First-line treatment with local percutaneous radiotherapy in combination with systemic interferon alfa-2a resulted in complete remission. However, 21 months later the disease progressed to T3N0M1B0/stage IVB with development of cerebral manifestation and thus very poor prognosis. Allogeneic stem cell transplantation (SCT) was not a therapeutic option due to the lack of a suitable donor. We initiated methotrexate and cytarabine chemotherapy, followed by high-dose chemotherapy with thiotepa and carmustine with autologous SCT. Despite rapid response and complete remission of the cerebral lesions, disease recurrence of the skin occurred soon after. Interestingly, readministration of interferon alfa-2a as a maintenance treatment after the salvage autologous SCT resulted in a durable complete remission during the follow-up period of currently 17 months after autologous SCT. What's already known about this topic? Mycosis fungoides is a primary cutaneous T-cell lymphoma with unfavourable prognosis for the advanced stages of the disease. A refractory course of disease requires systemic therapy. What does this study add? We report on an unusual case of a patient with mycosis fungoides with cerebral involvement, in which a durable complete remission was achieved upon autologous stem cell therapy and interferon alfa-2a maintenance therapy.

Interventions to improve adherence to tuberculosis treatment: systematic review and meta-analysis.

SETTING: One of the most serious problems in tuberculosis (TB) control is non-adherence to treatment. Several strategies have been developed to improve adherence and increase the cure rate. OBJECTIVE: To systematically review interventions to improve adherence to anti-tuberculosis treatment. DESIGN: We performed a systematic review and meta-analysis of 22 randomised clinical trials (RCTs) to ascertain whether providing directly observed treatment, short-course (DOTS), financial incentives, food incentives and/or patient education/counselling improved adherence to anti-tuberculosis treatment. The primary outcome was cure rate; secondary outcomes were default and mortality rates. Sources used were Medline (accessed via PubMed), Cochrane Central, LILACS (Literatura Latino Americana em Ciências da Saúde, Latin American and Caribbean Health Sciences Literature) and Embase from inception to October 2015. RESULTS: A significant increase in cure rates, by 18% with DOTS and by 16% with patient education and counselling, was observed. In addition, the default rate decreased by 49% with DOTS, by 26% with financial incentives and by 13% with patient education and counselling. There was no statistically significant reduction in mortality rates with these interventions. CONCLUSION: Use of DOTS and patient education/counselling significantly improved cure rates; DOTS, patient education/counselling and financial incentives led to a reduction in the default rate.

[Importance of investigation of fetal eyes : Supplement to fetal autopsy]. / Bedeutung der Untersuchung fetaler Augen : Ergänzung der Fetobduktion.

The investigation of fetal eyes is a subspecialty, which is performed by only a few ophthalmic pathologists and pathologists in specialized centers. If a certain fetal syndrome is suspected, the fetal eyes should be removed and submitted for ophthalmic pathological investigation in a specialized center. This can provide additional diagnostic information allowing a final classification of a syndrome and the comprehensive genetic counselling of parents with respect to future pregnancies. This article provides an overview of the histopathological findings in fetal eyes, which are of particular relevance for the pediatric pathological autopsy. In addition, the basic points of ocular development, the preparation of fetal eyes and frequent artifacts are presented.

[Stillbirths in Germany: Retrospective Analysis of 168 Cases between 2003 and 2011]. / Totgeburten in Deutschland: Retrospektive Datenanalyse von 168 Fällen zwischen 2003 und 2011.

BACKGROUND: The decline in the incidence of stillbirths in Germany has remained static in recent years. This study aims to analyse the current situation of data documentation and examination of stillbirths. Furthermore, possible stillbirth prevention strategies should be developed. METHODS: Searches in the international peer-reviewed literature, retrospective data collection of 168 stillbirths in 8 hospitals, (in the area of Bonn) with subsequent statistical evaluation (descriptive statistics, t-test and binominal test) were undertaken. RESULTS: This study shows considerable deficits in data documentation, interdisciplinary communication and postmortal examination. Only in 51.8% (87/168) of the cases was a certain or uncertain cause of death found (42.3% placental, 1.2% foetal, 3.6% chromosomal, 4.8% umbilical cord abnormalities). Severe foetal growth restriction (<5(th) percentile) was observed in 29.2%; 44.9% (22/49) of them died at the age of ≥36+0 weeks of gestation. CONCLUSION: The first step to reduce the rate of stillbirths in Germany is to increase the identified causes of foetal death: Therefore, an interdisciplinary case report form was compiled to improve data collection and interdisciplinary collaboration. To standardise and complete postmortal management, an algorithm was created. The long-term aim is the development of a central data register for statistical analysis, to identify goals of research and to organise conferences with interdisciplinary reports of diagnostic findings.

Pcgf6, a polycomb group protein, regulates mesodermal lineage differentiation in murine ESCs and functions in iPS reprogramming.

Polycomb group (PcG) proteins comprise evolutionary conserved factors with essential functions for embryonic development and adult stem cells. PcG proteins constitute two main multiprotein polycomb repressive complexes (PRC1 and PRC2) that operate in a hierarchical manner to silence gene transcription. Functionally distinct PRC1 complexes are defined by Polycomb group RING finger protein (Pcgf) paralogs. So far, six Pcgf paralogs (Pcgf1-6) have been identified as defining components of different PCR1-type complexes. Paralog-specific functions are not well understood. Here, we show that Pcgf6 is the only Pcgf paralog with high expression in undifferentiated embryonic stem cells (ESCs). Upon differentiation Pcgf6 expression declines. Following Pcgf6 kockdown (KD) in ESCs, the expression of pluripotency genes decreased, while mesodermal- and spermatogenesis-specific genes were derepressed. Concomitantly with the elevated expression of mesodermal lineage markers, Pcgf6 KD ESCs showed increased hemangioblastic and hematopoietic activities upon differentiation suggesting a function of Pcgf6 in repressing mesodermal-specific lineage genes. Consistant with a role in pluripotency, Pcgf6 replaced Sox2 in the generation of germline-competent induced pluripotent stem (iPS) cells. Furthermore, Pcgf6 KD in mouse embryonic fibroblasts reduced the formation of ESC-like colonies in OSKM-driven reprogramming. Together, these analyses indicate that Pcgf6 is nonredundantly involved in maintaining the pluripotent nature of ESCs and it functions in iPS reprogramming.

Coronal clefts in infants - rare differential diagnosis of traumatic injuries of vertebral bodies in battered children.

Accidental and nonaccidental spinal injuries are generally rarely seen in infants. If affected, vertebral bodies usually present compression fractures due to forced hyperflexion or hypertension. Radiographic examination of the infantile skeleton can reveal a radiolucent band running through a vertebral body. These so called vertebral clefts are mainly visualized in the lateral spinal radiograph. Usually they can be found in the 1st year of life. Radiological appearance of coronal clefts was compared to that of a traumatic vertebral compression fracture. Clefts were mostly localized in the lumbar spine and had a completely different radiological appearance comparing to a traumatic compression fracture. As coronal clefts can be seen as a result from a retarded ossification of the vertebral bodies in fetal development they are a physiological variant. Due to this different etiology they have to be distinguished from spinal signs of child abuse.

LPS-induced effects on angiotensin I-converting enzyme expression and shedding in human pulmonary microvascular endothelial cells.

Angiotensin I-converting enzyme (kininase II, ACE, and CD143) availability is a determinant of local angiotensin and kinin concentrations and their physiological actions. Until now, it is unclear whether the decrease of pulmonary ACE activity in sepsis-described in clinical studies-is due to an enzyme compensatory downregulation (reduced ACE-mRNA expression) to shedding of ACE or endothelial damage. To address these questions, ACE distribution under septic conditions was studied in vitro by treating pulmonary microvascular endothelial cells (HPMEC) and human umbilical vein endothelial cells (HUVEC) with lipopolysaccharide from Escherichia coli (LPS). Primary isolated HUVEC and HPMEC were compared by detecting ACE activity, membrane-bound ACE, as well as shedding and mRNA production of ACE with and without LPS (1 ng/ml-1 µg/ml). ACE mRNA expression was detected by real-time PCR, and shedded ACE was measured in cell culture supernatant by ELISA. Additionally, membrane-bound protein expression was investigated by immunohistochemistry in situ. In septic ARDS, the distribution of ACE protein was significantly reduced in all lung endothelial cells (p<0.001). After stimulation with LPS, cultivated HPMEC showed more markedly than HUVEC, a concentration-dependent reduction of ACE protein expression compared to the respective untreated controls. Real-time PCR demonstrated a reduced ACE mRNA expression after LPS stimulation, predominantly in HPMEC. Specifically, in HPMEC, a concentration-dependent increase of shedded ACE was shown 24 h after LPS treatment. HPMEC cultures are an apt model for the investigation of pulmonary ACE expression in sepsis. This study suggests that reduced pulmonary microvascular endothelial ACE expression in septic ARDS is caused by two processes: (initial) increased shedding of ACE accompanied by a compensatory downregulation of ACE-mRNA and membrane-bound protein expression.