Herpes Zoster in Breast Cancer Patients after Radiotherapy

Background: We have studied the incidence of herpes zoster in patients with adjuvant radiotherapy for breast cancer with special emphasis on possible correlations with other prognostic factors or survival. Patients and Methods: From 1/1985 through 12/1993, 1 155 breast cancer patients received postoperative radiotherapy with curative interent in our department. After mastectomy 961 patients were irradiated and after breast-preserving treatment 194 patients. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3 to 12.4 years). There were 443 women (38%) pre- and 712 (62%) postmenopausal. 21% had T3- to T4-tumors, 55% had axillary lymph node involvement, and 65% received additional systemic hormonal and/or cytotoxic therapy. In case of postmastectomy radiotherapy, the lateral chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field to 50 Gy (axilla 44 Gy) and most of the chest wall with an electron field to 44 Gy in 2-Gy fractions. After breast-preservation, the breast was irradiated via tangential fields with 6- to 8-MV photons up to 50 Gy plus 8 Gy electron boost to the tumor bed. Most of the patients were followed routinely in the department for 2 to 5 years. The frequency of zoster was determined retrospectively by reviewing the patients' records. Results: A zoster after radiotherapy occurred in 41/1 155 patients (3.7%), mostly within the first 2 years after completion of radiotherapy. All infections remained localized and there was no evidence for systemic infections. Type of treatment (mastectomy vs breast-preservation) had no impact on the frequency of herpes zoster (36/961 patients after mastectomy and 5/194 patients after breast-preservation). There was also no correlation with other prognostic factors such as age, menopausal status, stage of disease or the use of adjuvant chemotherapy, nor was the occurrence of zoster linked to the degree of acute skin reaction in the radiation field. Moreover, patients with zoster had the same prognosis as compared to patients without zoster with regard to local control and survival. Conclusions: The observed frequency of zoster (about 4% of patients after postoperative radiotherapy) in this retrospective study suggests that the risk of developing zoster in this patient group may be 3- to 5-fold higher as compared to the incidence in the general population. However, the occurrence of zoster was not linked to prognosis and treatment response. Hintergrund: Wir haben in einer retrospektiven Analyse die Häufigkeit eines Herpes zoster bei Patientinnen mit Mammakarzinom und postoperativer Radiotherapie untersucht. Patientinnen und Methode: Von Januar 1985 bis Dezember 1993 erhielten 1 155 Patientinnen an unserer Klinik eine postoperative Bestrahlung nach Mastektomie (n = 961) oder brusterhaltende Operation (n = 194) in kurativer Intention. Das Alter betrug 34 bis 79 Jahre. 443 (38%) waren prä- und 712 (62%) postmenopausal, 21% hatten T3- bis T4-Tumoren, und 55% wiesen einen axillären Lymphknotenbefall auf. Alle Patientinnen erhielten eine Bestrahlung der Restbrust bzw. Thoraxwand bis 50 Gy, bei mastektomierten Patientinnen wurden zusätzlich die regionären Lymphknoten mit 44 Gy bestrahlt. 65% der Patientinnen erhielten eine zusätzliche Systemtherapie. Die Nachbeobachtungszeit betrug drei Monate bis 12,5 Jahre (Median 3,1 Jahre). Ergebnisse: 41/1 155 Patientinnen (3,7%) entwickelten im Nachbeobachtungszeitraum einen Herpes zoster. Alle Infektionen waren lokalisiert, eine generalisierte Hautinfektion oder systemische Infektionen traten nicht auf. Alter, Menopausenstatus, Erkrankungsstadium oder Art der Therapie (Brusterhaltung vs. Mastektomie, zusätzliche Chemotherapie) hatten keinen Einfluss auf die Frequenz von Zoster. Patientinnen mit starker akuter Hautreaktion waren ebenfalls nicht signifikant stärker betroffen als Patientinnen mit geringer Hautreaktion im Bestrahlungsfeld (5% vs. 2%). Das Auftreten eines Zosters nach Therapie hatte keinen Einfluss auf die Prognose hinsichtlich lokaler Kontrolle oder Überleben. Schlussfolgerungen: Die beobachtete Häufigkeit von Herpes zoster (etwa 4% nach drei Jahren Follow-up) lässt vermuten, dass ein Herpes zoster im untersuchten Kollektiv etwa drei- bis fünffach häufiger auftritt als anhand der Inzidenzen in der Normalbevölkerung erwartet. Dies ist nicht mit einer schlechteren Prognose assoziiert. Ob die erhöhte Frequenz auf die Radiotherapie zurückzuführen ist oder in Zusammenhang mit der Krebserkrankung steht, kann nich beurteilt werden.     

Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience

Chronic infectious rhinosinusitis with Pseudomonas aeruginosa is common in cystic fibrosis and may result in allograft infection after lung transplantation. Sinus surgery followed by nasal care may reduce these adverse effects. Sinus surgery was performed in 37 patients with cystic fibrosis after transplantation. Bacteriology of sinus aspirates (n=771) and bronchoalveolar lavage (BAL) (n=256) was correlated with clinical data. Sinus surgery was successful in 54% and partially successful in 27% of patients. A significant correlation between negative sinus aspirates and negative BAL and between positive sinus aspirates and positive BAL (P<0.0001) was found. Successful sinus management led to a lower incidence of tracheobronchitis and pneumonia (P=0.009) and a trend toward a lower incidence of bronchiolitis obliterans syndrome (P=0.23). Sinus surgery followed by daily nasal douching may control posttransplant lower airway colonization and infection. In the long term, this concept may lead to less bronchiolitis obliterans syndrome by decreasing bronchiolar inflammation.     

Outcome of surgery for ileojejunal neuroendocrine tumors

Purpose

Neuroendocrine tumors (NET) of the ileum/jejunum are rare and may require different treatment options to provide long-term survival. The purpose of the study was to evaluate the outcome of surgery for ileojejunal NET.

Methods

A database of patients that underwent surgery for ileojejunal NETs between 1999 and 2010 was retrospectively analyzed regarding the clinical characteristics, surgical therapy, survival and prognostic factors.

Results

Only six of 97 patients with ileojejunal NET who underwent surgery had localized tumors (stage I/II), 29 had lymph node involvement (stage III) and 62 had distant metastases (stage IV) at the initial presentation. All stage I/II tumors were cured, in comparison to 69 % of stage III and 0 % of stage IV tumors (p = 0.01). Palliative surgery in combination with sequential multimodal treatment regimens resulted in a 5-year survival rate of 63 % in patients with stage IV tumors. A multivariate analysis showed that incomplete resection (HR 2.87; CI 1.18–6.98; p = 0.04) and distant metastases (HR 5.39; 95 % CI 1.23–23.57; p = 0.02) were associated with worse disease-specific survival.

Conclusions

Localized and regionally restricted ileojejunal NETs have an excellent prognosis after surgical treatment. Although stage IV tumors cannot be cured, an aggressive surgical approach in combination with medical or interventional treatment can provide long-term survival.     

American Society of Neuroradiology research survey 2001

RATIONALE AND OBJECTIVES: Research is a critical component of the mission of academic radiology, and success in research is necessary for the future of neuroradiology. Thus, the authors set out to establish a baseline of research activities of American Society of Neuroradiology (ASNR) members. MATERIALS AND METHODS: The authors surveyed 100 fellowship program directors. The survey was Web based, with recruitment from the ASNR Fellowship Database survey site and with e-mail and fax solicitations to the Web site. Questions focused on neuroradiologist and neuroradiology fellow involvement in research. RESULTS: Forty-eight of the 100 program directors (48%) responded. Several key findings emerged: (a) About one-third of fellowship programs require all fellows to do some research, with most fellows receiving less than 1 day per week of academic time; (b) just over half of the programs expect fellows to publish a paper; (c) about two-thirds of academic neuroradiologists get at least 1 academic day per week; (d) most academic neuroradiologists perform research, but most of this research is unfunded; and (e) about nine of 10 academic sections have at least one neuroradiologist with some extramural funding. CONCLUSION: The relative lack of extramural funding among academic neuroradiologists is a reality that is probably multifactorial; however, there may be a direct relationship between amount of academic time free from clinical duties and successful competition for funding. The time (and, thus, financial) support of research-oriented fellows and faculty should be increased.     

Suicide rates in five-year age-bands after the age of 60 years: the international landscape†

Background: There is paucity of studies examining suicide rates in narrow five-year age-bands after the age of 60 years. This study examined suicide rates in eight five-year age-bands between the age of 60 and 99 years because this will allow more precise comparison between the young old (60–79 years) and the oldest old (80+ years) age groups.

Methods: Data on the number of suicides (International Classification of Diseases – ICD-10 codes, X60-84) in each of the eight five-year age-bands between the age-bands 60–64 years and 95–99 years in both gender for as many years as possible from 2000 were ascertained from three sources: colleagues with access to national data, national statisics office websites and email contact with the national statistics offices. The population size for the corresponding years and age-bands was estimated for each country using data provided by the United Nations website.

Results: In men, suicide rates continued to increase for each of the seven five-year age-bands from 60–64 years to 90–94 years age-band, and then declined slightly for the 95–99 year age-band. In women, suicide rates continued to increase for each of the six five-year age-bands from 60–64 years to 85–89 years age-bands, and then declined slightly for the 90–94 years and 95–99 years age-bands.

Conclusions: The overall global suicide rates for each of the eight five-year age-bands are sufficiently large for them to constitute a public health concern. This is especially important given the ongoing rise in the elderly population size and the paucity of data on risk and protective factors for suicide in the five-year age-bands after the age of 60 years.     

The contribution of inner and outer retinal photoreceptors to infra‐slow oscillations in the rat olivary pretectal nucleus

A subpopulation of olivary pretectal nucleus (OPN) neurons discharges action potentials in an oscillatory manner, with a period of approximately two minutes. This ‘infra‐slow’ oscillatory activity depends on synaptic excitation originating in the retina. Signals from rod‐cone photoreceptors reach the OPN via the axons of either classic retinal ganglion cells or intrinsically photosensitive retinal ganglion cells (ipRGCs), which use melanopsin for photon capturing. Although both cell types convey light information, their physiological functions differ considerably. The aim of the present study was to disentangle how rod‐cone and melanopsin photoresponses contribute to generation of oscillatory activity. Pharmacological manipulations of specific phototransduction cascades were used whilst recording extracellular single‐unit activity in the OPN of anaesthetized rats. The results show that under photopic conditions (bright light), ipRGCs play a major role in driving infra‐slow oscillations, as blocking melanopsin phototransmission abolishes or transiently disturbs oscillatory firing of the OPN neurons. On the other hand, blocking rod‐cone phototransmission does not change firing patterns in photopic conditions. However, under mesopic conditions (moderate light), when melanopsin phototransmission is absent, blocking rod‐cone signalling causes disturbances or even the disappearance of oscillations implying that classic photoreceptors are of greater importance under moderate light. Evidence is provided that all photoreceptors are required for the generation of oscillations in the OPN, although their roles in driving the rhythm are determined by the lighting conditions, consistent with their relative sensitivities. The results further suggest that maintained retinal activity is crucial to observe infra‐slow oscillatory activity in the OPN.     

Microglia replenished OHSC: A culture system to study in vivo like adult microglia

Recent data suggest that ramified microglia fulfil various tasks in the brain. However, to investigate this unique cell type cultured primary microglia are only a poor model. We here describe a method to deplete and repopulate organotypic hippocampal slice cultures (OHSC) with ramified microglia isolated from adult mouse brain creating microglia‐replenished OHSC (Mrep‐OHSC). Replenished microglia integrate into the tissue and ramify to a degree indistinguishable from their counterparts in the mouse brain. Moreover, wild‐type slices replenished with microglia from TNFα‐deficient animals provide similar results as OHSC prepared from microglia‐specific TNFα‐knockout mice (CX3CR1^cre/TNFα^fl/fl). Furthermore, this study demonstrates that replenished microglia in OHSC maintain original functions and properties acquired in vivo. Microglia from ERCC1^Δ/ko mice, a mouse model of accelerated aging, maintain enhanced Mac2 expression and their activated phenotype after replenishment to wild‐type OHSC tissue. Thus, the present study demonstrates that Mrep‐OHSC are a unique tool to construct chimeric brain slices allowing studying the function of different phenotypes of in vivo like microglia in a tissue culture setting. GLIA 2016 GLIA 2016;64:1285–1297     

Adult patients with sporadic polycystic kidney disease: the importance of screening for mutations in the PKD1 and PKD2 genes

Background

ADPKD is one of the most common inherited disorders, with high risk for end-stage renal disease. Numerous patients, however, have no relatives in whom this disorder is known and are unsure whether they may transmit the disease to their offsprings. The aim of this study was to evaluate whether germline mutation analysis adds substantial information to clinical symptoms for diagnosis of ADPKD in these patients.

Methods

Clinical data included renal function and presence of liver or pancreas cysts, heart valve insufficiency, intracranial aneurysms, colonic diverticles, and abdominal hernias. Family history was evaluated regarding ADPKD. Germline mutation screening of the PKD1 and PKD2 genes was performed for intragenic mutations and for large deletions.

Results

A total of 324 adult patients with ADPKD including 30 patients without a family history of ADPKD (sporadic cases) were included. PKD1 mutations were found in 24/30 and PKD2 mutations in 6 patients. Liver cysts were present in 14 patients and intracranial aneurysms in 2 patients. Fourteen patients (45%) had no extrarenal involvement. Compared to the 294 patients with familial ADPKD, the clinical characteristics and the age at the start of dialysis were similar in those with sporadic ADPKD.

Conclusion

The clinical characteristics of patients with sporadic and familial ADPKD are similar, but sporadic ADPKD is often overlooked because of the absence of a family history. Molecular genetic screening for germline mutations in both PKD1 and PKD2 genes is essential for the definitive diagnosis of ADPKD.     

Molecular absorbent recirculating system for the treatment of acute liver failure in surgical patients

The Molecular Adsorbent Recirculating System (MARS) represents an attractive artificial liver support system for the treatment of liver insufficiency. However, neither indications for MARS treatment (i.e., after extended liver resection) nor criteria for discontinuation of therapy have been evaluated. Therefore, we analyzed the clinical data of all our surgical patients who received MARS treatment for acute liver failure (n = 7). The aim of the study was to identify prognostic indicators for survival. Four of 174 patients resected for hepatic malignancy at our institution received a total of 13 MARS treatments. Two additional patients were successfully bridged to orthotopic liver transplantation with seven MARS treatments and one patient was MARS supported after liver transplantation of a steatotic graft with three MARS treatments. Five of the seven patients survived and were dismissed an average of 31 days, ranging from 17 to 47 days, after the final MARS treatment. No technical complications or adverse effects were observed during the MARS treatments. Important prognostic factors for hepatic recovery and survival were indocyanin green plasma disappearance rates greater than 5%/min and an increase in clotting factor V levels after each MARS treatment. We conclude that MARS therapy can be an effective treatment of postoperative liver insufficiency in the surgical hepatobiliary unit. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review

Background

Long-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation.

Method

In this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6–12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology.

Impact

This integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.