Does Hospital Operative Volume Influence the Outcomes of Patients After Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis?

BACKGROUND: For some cancer operations, center volume is associated with improved patient outcomes. Whether this association is true for cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unclear. Given the rapidly expanding use of CRS/HIPEC, the aim of this analysis was to determine whether a volume-outcome relationship exists for this strategy. METHODS: The Vizient Clinical Database® was queried for CRS/HIPEC cases from January 2020 through December 2022. Low-, medium-, and high-volume designations were made by sorting hospitals by case volume and creating equal tertiles based on total number of cases. Analysis was performed via one-way ANOVA with post-hoc Tukey test, as indicated. RESULTS: In the 36-month study period, 5165 cases were identified across 149 hospitals. Low- (n = 113), medium- (n = 25), and high-volume (n = 11) centers performed a median of 4, 21, and 47 cases per annum, respectively. Most cases were performed for appendiceal (39.3%) followed by gynecologic neoplasms (20.4%). Groups were similar with respect to age, gender, race, comorbidities, and histology. Low-volume centers were more likely to utilize the ICU post-operatively (59.6% vs. 40.5% vs. 36.3%; p = 0.02). No differences were observed in morbidity (9.4% vs. 7.1% vs. 9.0%, p = 0.71), mortality (0.9% vs. 0.6% vs. 0.7%, p = 0.93), length of stay (9.3 vs. 9.4 vs. 10 days, p = 0.83), 30-day readmissions (5.6% vs. 5.6% vs. 5.6%, p = 1.0), or total cost among groups. CONCLUSIONS: No association was found between CRS/HIPEC hospital volume and post-operative outcomes. These data suggest that in academic medical centers with HIPEC programs, outcomes for commonly treated cancers are not associated with hospital volume.

Comparing Functional Frailty and Radiographic Sarcopenia as Predictors of Outcomes After Liver Transplant.

INTRODUCTION: Frailty and sarcopenia are associated with an increased risk of hospitalization and mortality in patients with end-stage liver disease. The ability to identify frail patients at risk of adverse outcomes could help optimize liver transplant (LT) evaluations and pre-transplant care. This study compared sarcopenia, via L3-psoas muscle index (L3-PMI), to frailty, via liver frailty index (LFI) and analyzed associated outcomes after liver transplantation (LT). METHODS: A retrospective review of consecutive LT-recipients with cross-sectional abdominal/pelvic imaging were reviewed over 5 years at a single transplant center. RESULTS: Four hundred and twenty-six patients underwent transplant during this study interval; 31% of patients were sarcopenic. Two hundred eight patients underwent LFI evaluation: 25% were frail, 59% were prefrail, and 16% were robust. Sarcopenic patients had higher LFI scores indicating greater frailty (p = 0.02). Both sarcopenia and LFI-frailty were associated with significantly higher MELD-Na scores. Length of post-LT hospital stay was increased in sarcopenic (mean 14 vs. nonsarcopenic 11 days, p = 0.02) and LFI-frail patients (mean 13 vs. 10 prefrail, 8 robust, p = 0.04). As a categorical variable, neither LFI-frailty nor sarcopenia were significantly associated with reduced survival at 1-year (robust 100%, prefrail 93.5%, frail 91.1%, p = 0.31) (nonsarcopenic 94.4%, sarcopenic 91.4%, p = 0.30). However, LFI score was significantly associated with mortality at 1-year (OR 2.133, p = 0.047). CONCLUSIONS: Radiographic sarcopenia is a suitable proxy for in-person frailty assessment as both L3-PMI and LFI capture frail patients' pre-LT. However, physical assessment with frailty better predicts 1-year mortality post-LT than the measurement of muscle mass.

Enhancing Occupant Comfort and Building Sustainability: Lessons from an Internet of Things-Based Study on Centrally Controlled Indoor Shared Spaces in Hot Climatic Conditions.

It is well known that buildings have a sizeable energy and environmental footprint. In particular, in environments like university campuses, the occupants as well as occupancy in shared spaces varies over time. Systems for cooling in such environments that are centrally controlled are typically threshold driven and do not account for occupant feedback and thus are often relying on a reactive approach (fix after identifying problems). Therefore, having a fixed thermal operating set point may not be optimal in such cases-both from an occupant comfort and well-being as well as an energy efficiency perspective. To address this issue, a study was conducted which involved development and deployment of an experimental Internet of Things (IoT) prototype system and an Android application that facilitated people engagement on a university campus located in the UAE which typically exhibits hot climatic conditions. This paper showcases data driven insights obtained from this study, and in particular, how to achieve a balance between the conflicting goals of improving occupant comfort and energy efficiency. Findings from this study underscore the need for regular reassessments and adaptation. The proposed solution is low cost and easy to deploy and has the potential to reap significant savings through a reduction in energy consumption with estimates indicating around 50-100 kWh/day of savings per building and the resulting environmental impact. These findings would appeal to stakeholders who are keen to improve energy efficiency and reduce their operating expenses and environmental footprint in such climatic conditions. Furthermore, collective action from a large number of entities could result in significant impact through this cumulative effect.

N- and O-glycosylation patterns and functional testing of CGB7 versus CGB3/5/8 variants of the human chorionic gonadotropin (hCG) beta subunit.

The classical function of human chorionic gonadotropin (hCG) is its role in supporting pregnancy. hCG is a dimer consisting of two highly glycosylated subunits, alpha (CGA) and beta (CGB). The beta-hCG protein is encoded by CGB3, CGB5, CGB7 and CGB8 genes. CGB3, 5 and 8 code for an identical protein, CGB3/5/8, whereas CGB7 differs in three amino acids from CGB3/5/8. We had observed earlier that CGB7 and CGB3/5/8 display very distinct tissue expression patterns and that the tumor suppressor and transcription factor p53 can activate expression of CGB7 but not of CGB3/5/8 genes. Here, we investigate the glycan structures and possible functional differences of the two CGB variants. To this end, we established a system to produce and isolate recombinant CGA, CGB7 and CGB3/5/8 proteins. We found that N- and O-glycosylation patterns of CGB7 and CGB3/5/8 are quite similar. Functional assays were performed by testing activation of the ERK1/2 pathway and demonstrated that CGB7 and CGB5/5/8 appear to be functionally redundant isoforms, although a slight difference in the kinetics of ERK1/2 pathway activation was observed. This is the first time that biological activity of CGB7 is shown. In summary, the results lead to the hypothesis that CGB7 and CGB3/5/8 do not hold significant functional differences but that timing and cell type of their expression is the key for understanding their divergent evolution.

The aquaporin-4 inhibitor AER-271 blocks acute cerebral edema and improves early outcome in a pediatric model of asphyxial cardiac arrest.

BACKGROUND: Cerebral edema after cardiac arrest (CA) is associated with increased mortality and unfavorable outcome in children and adults. Aquaporin-4 mediates cerebral water movement and its absence in models of ischemia improves outcome. We investigated early and selective pharmacologic inhibition of aquaporin-4 in a clinically relevant asphyxial CA model in immature rats in a threshold CA insult that produces primarily cytotoxic edema in the absence of blood-brain barrier permeability. METHODS: Postnatal day 16-18 Sprague-Dawley rats were studied in our established 9-min asphyxial CA model. Rats were randomized to aquaporin-4 inhibitor (AER-271) vs vehicle treatment, initiated at return of spontaneous circulation. Cerebral edema (% brain water) was the primary outcome with secondary assessments of the Neurologic Deficit Score (NDS), hippocampal neuronal death, and neuroinflammation. RESULTS: Treatment with AER-271 ameliorated early cerebral edema measured at 3 h after CA vs vehicle treated rats. This treatment also attenuated early NDS. In contrast to rats treated with vehicle after CA, rats treated with AER-271 did not develop significant neuronal death or neuroinflammation as compared to sham. CONCLUSION: Early post-resuscitation aquaporin-4 inhibition blocks the development of early cerebral edema, reduces early neurologic deficit, and blunts neuronal death and neuroinflammation post-CA.

Endometrial human chorionic gonadotropin (hCG) expression is a marker for adequate secretory transformation of the endometrium.

PURPOSE: Successful embryo implantation into the endometrium depends on embryonic characteristics and proper endometrial development. Reproductive medicine often focuses on embryo quality, whereas reliable diagnostic tests for endometrial receptivity are still needed. We previously found that human chorionic gonadotropin (hCG), one of the earliest proteins secreted by the embryo, was also expressed by the luteal phase endometrium around the implantation window. Here, we tested our hypothesis of endometrial hCG as an implantation marker. METHODS: Endometrial biopsies and serum samples were taken from patients undergoing routine infertility diagnostics. Correlations of immunohistochemically detected endometrial hCG expression with adequate endometrial secretory transformation, the infiltration of CD45-positive leukocytes, clinical diagnostic parameters, and endometrial thickness were analyzed. RESULTS: A highly significant correlation between the endometrial score, as a measurement for regular secretory transformation, and the intensity of hCG staining was found. The invasion of CD45-positive leukocytes increased with progressing endometrial secretory transformation and rising endometrial hCG expression. In addition, serum progesterone concentrations correlated with hCG expression by the endometrial glands. CONCLUSIONS: Our results suggest endometrial hCG as a possible diagnostic parameter characterizing the endometrial secretory transformation and, thus, possibly also its implantation capability.

Identification and prediction of the fertile window with a new web-based medical device using a vaginal biosensor for measuring the circadian and circamensual core body temperature.

Fertility awareness-based (FAB) methods represent a term that includes all family planning methods that are based on the identification of the fertile window. They are based on the woman's observation of physiological signs of the fertile and infertile phases of the menstrual cycle. The first approach consists basically in symptothermal methods accompanied by cervical mucus measurements and clinical menstrual cycling data recording. The second most often used methods are the urinary measurement of E3G and luteinizing hormone (LH) with a personalized computer system. Hence these systems lack the efficacy of the continuous circadian and circamensual measurement of the core body temperature. Only this approach enables the accurate detection of the ovulation during the fertile window. A new medical device called OvulaRing has been developed to fill this gap. In the present study, the system and its first clinical results are presented. OvulaRing is a medical device used just like a tampon. The device is a vaginal ring of evatane that contains an integrated biosensor. This sensor measures continuously every 5 min the core body temperature throughout the entire cycle. This device allows a circadian and circamensual intravaginal exact measurement. With this system, 288 measurements are created per day. The system can detect retrospectively and predict prospectively the fertile window of the users. One hundred and fifty eight women aged between 18 and 45 years used this medical device in an open non-randomized clinical study for 15 months. A total of 470 cycles could be recorded and were able for analysis. By the same time in a subgroup of patients, hormonal assessments of LH, follicle-stimulating hormone, estradiol and progesterone as well as vaginal ultrasound were performed in parallel between the 9th and the 36th day of the cycle. The validation error due to software errors was 0.89% for the retrospective analysis; that means that the accuracy for the detection of the ovulation was 99.11%. Accuracy of 88.8% for a window of 3 days before ovulation, the day of ovulation and the 3 days after ovulation was achieved for the prospective analysis. In the subgroup of woman with recorded pregnancies, it could be shown that after 3.79 months of use (median) pregnancies were observed. In 67.72% in up to 3 months, in 16.36% between 3 and 6 months of use, in 7.27% between 7 and 9 months, in 5.45% between 10 and 12 months and in 1.82% between 13 and 15 months of use of the system. With this new web-based system, a precise determination of the fertile window even in women with ultralong cycles (>35 days) could be detected independently of their personal live circumstances. Exact determination of the fertile window is herewith possible so that OvulaRing represents an evolution in the FAB method for the cycle diagnosis of women with regular, irregular or anovulatory menstrual cycles.

Spinal cord constraints in the era of high-precision radiotherapy : Retrospective analysis of 62 spinal/paraspinal lesions with possible infringements of spinal cord constraints within a minimal volume.

OBJECTIVE: Current constraints aim to minimize the risk of radiation myelitis by the use of restrictive maximal spinal cord doses, commonly 50 Gy. However, several studies suggested that a dose-volume effect could exist. Based on these observations, we evaluated patients receiving potentially excessive doses to the spinal cord within minimal volumes. PATIENTS AND METHODS: Patients receiving radiotherapy between June 2010 and May 2015 using the NovalisTM (Varian, Palo Alto, CA, USA; Brainlab, Heimstetten, Germany) radiosurgery system were retrospectively analyzed. A total of 56 patients with 62 treated lesions that had been prescribed radiation doses close to the spinal cord potentially higher than the common 50 Gy 2­Gy equivalent-dose (EQD2) constraint were selected for further analysis. Of these patients, 26 with 31 lesions had no history of previous irradiation, while 30 patients with 31 lesions had been previously irradiated within the treatment field. RESULTS: According to different dose evaluation approaches (spinal canal, spinal cord contour), 16 and 10 out of 31 primary irradiated lesions infringed constraints. For the 16 lesions violating spinal canal doses, the maximum doses ranged from 50.5 to 61.9 Gy EQD2. Reirradiated lesions had an average and median cumulative dose of 70.5 and 69 Gy, respectively. Dose drop-off was steep in both groups. Median overall survival was 17 months. No radiation myelitis or radiomorphological alterations were observed during follow-up. CONCLUSION: This study adds to the increasing body of evidence indicating that excessive spinal cord doses within a minimal volume, especially in a reirradiation setting with topographically distinct high-point doses, may be given to patients after careful evaluation of treatment- and tumor-associated risks.

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

BACKGROUND: Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO2) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO2-targeted therapies, we propose to determine if CBF and PbO2 disturbances persist at 24 h after experimental pediatric CA. METHODS: Regional CBF and PbO2 were measured at 24 h after asphyxial CA in immature rats (n = 26, 6-8/group) using arterial spin label MRI and tissue electrodes, respectively. RESULTS: In all regions but the thalamus, CBF recovered to sham values by 24 h; thalamic CBF was >32% higher after CA vs. sham. PbO2 values at 24 h after CA in the cortex and thalamus were similar to shams in rats who received supplemental oxygen, however, on room air, cortical PbO2 was lower after CA vs. shams. CONCLUSION: CBF remains increased in the thalamus at 24 h after CA and PbO2 is decreased to hypoxic levels in cortex at 24 h after CA in rats who do not receive supplemental oxygen. Given the enduring disturbances in this model and the lack of routine CBF or PbO2 monitoring in patients, our data suggest the need for clinical correlation.

Comparative treatment planning study on sequential vs. simultaneous integrated boost in head and neck cancer patients: Differences in dose distributions and potential implications for clinical practice.

AIM: The purpose of this work was to compare sequential (SeqB) versus simultaneous integrated boost (SIB) radiotherapy plans delivered with volumetric modulated arc therapy (VMAT) for patients with locally advanced squamous cell cancer of the head and neck (HNSCC). PATIENTS AND METHODS: SeqB and SIB plans using VMAT for 10 HNSCC patients given definitive chemoradiation were generated and analysed for differences in dose distribution, coverage, conformity and homogeneity to the planning target volumes (PTV) 1-3 and sparing of organs at risk (OAR). RESULTS: The mean delineated volumes ± standard deviations were 137.7 ± 44.8, 351.3 ± 83.9 and 895.6 ± 120.5 cm3 for PTV1-3. The mean volumes encompassed by the corresponding 95 % isodoses were 281 (+ 110 %) ± 73.4, 712.2 (+ 115 %) ± 146.4 and 1381.1 (+ 54 %) ± 217.3 cm3 with SeqB and 138.2 (+ 7 %) ± 40.1, 380.4 (+ 11 %) ± 91.9 and 1057.3 (+ 21 %) ± 161.4 cm3 with SIB for PTV1-3, respectively. Both strategies achieved excellent PTV coverage. SeqB provided significantly better coverage of PTV1 and 3, worse conformity for PTV1-3 and a higher mean dose than prescribed (111-115 %) to PTV2 and 3 (p ≤ 0.007). Both strategies provided satisfactory OAR sparing. CONCLUSION: This study showed significant dosimetric differences with potential clinical relevance between two VMAT boost strategies regarding coverage, conformity and dose to the PTVs. SIB might cause less toxicity. A clinical phase III/IV trial endorsed by the German Head and Neck Clinical Trials Group (IAG-KHT) will evaluate differences in acute/late toxicity as well as in locoregional recurrences between the two boost techniques.

Brain tissue oxygen monitoring identifies cortical hypoxia and thalamic hyperoxia after experimental cardiac arrest in rats.

BACKGROUND: Optimization of cerebral oxygenation after pediatric cardiac arrest (CA) may reduce neurological damage associated with the post-CA syndrome. We hypothesized that important alterations in regional partial pressure of brain tissue oxygen (PbO2) occur after resuscitation from CA and that clinically relevant interventions such as hyperoxia and blood pressure augmentation would influence PbO2. METHODS: Cortical and thalamic PbO2 were monitored in immature rats subjected to asphyxial CA (9 or 12 min asphyxia) and sham-operated rats using oxygen sensors. RESULTS: Thalamus and cortex showed similar baseline PbO2. Postresuscitation, there was early and sustained cortical hypoxia in an insult-duration dependent fashion. In contrast, thalamic PbO2 initially increased fourfold and afterwards returned to baseline values. PbO2 level was dependent on the fraction of inspired O2, and the response to oxygen was more pronounced after a 9 vs. 12 min CA. After a 12 min CA, PbO2 was modestly affected by blood pressure augmentation using epinephrine in the thalamus but not in the cortex. CONCLUSION: After asphyxial pediatric CA, there is marked regional variability of cerebral oxygenation. Cortical hypoxia is pronounced and appears early, whereas thalamic hyperoxia is followed by normoxia. Compromised PbO2 in the cortex may represent a relevant and clinically measurable therapeutic target aimed at improving neurological outcome after pediatric CA.

Severe mucoid degeneration of the anterior cruciate ligament (ACL) treated with conservative arthroscopic debridement and platelet-rich plasma (PRP) injection.

Mucoid degeneration of the anterior cruciate ligament (ACL) can be treated with arthroscopic debridement, however, instability can ensue. Here, we present a fit and active woman in her 60s with severe mucoid degeneration of the ACL who underwent conservative arthroscopic debridement and treatment with intraligamentous administration of platelet-rich plasma (PRP). After 1 month, the patient demonstrated significant improvements in range of motion and pain symptoms, with nil resultant laxity. The patient was able to return to all recreational sporting activities and professional duties. Quantitative MRI conducted 6 months postoperatively revealed improved fibre orientation and formation of new parallel fibres. Compared with the preoperative scan, the mean grey value demonstrated darker pixel intensity with a smaller standard deviation (SD), potentially indicating a more uniform and less variable formation of ligamentous tissue. Therefore, PRP did not cause harm and was associated with benefit in combination with arthroscopic debridement.

Thalamocortical dysfunction and thalamic injury after asphyxial cardiac arrest in developing rats.

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia-ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic reticular nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on postnatal day 17. We found that 48-72 h after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6-8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine minutes of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the reticular nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest.

Clinical evaluation of a web-based personalized recommendation system with electronic health record interface to optimize healthcare resources during SARS-CoV-2 surges.

During the SARS-CoV-2 pandemic, the German healthcare system faced challenges of efficiently allocating testing resources. To address this, we developed an open-source personalized recommendation system (PRS) called "CovApp". The PRS utilized a questionnaire to estimate the risk of infection, provided personalized recommendations such as testing, self-isolation, or quarantine, and featured QR code data transmission to electronic health records. The PRS served up to 2.5 million monthly users and received 67,000 backlinks from 1800 domains. We clinically evaluated the PRS at the SARS-CoV-2 testing facility at Charité and observed a 21.7% increase in patient throughput per hour and a 22.5% increase in patients per day. Patients using the PRS were twice as likely to belong to the High Risk group eligible for testing (18.6% vs. 8.9%, p < 0.0001), indicating successful compliance with CovApp's recommendations. CovApp served as a digital bridge between the population and medical staff and significantly improved testing efficiency. As an open-source platform, CovApp can be readily customized to address emerging public health crises. Further, given the EHR interface, the app is of great utility for other applications in clinical settings.

Expression and production of human chorionic gonadotropin (hCG) in the normal secretory endometrium: evidence of CGB7 and/or CGB6 beta hCG subunit gene expression.

We have previously confirmed glandular cell CGB and CGA subunit mRNA gene expression as well as the expression of their dimeric and single-subunit human chorionic gonadotropin (hCG) proteins in normal secretory transformed endometrium. The objective of this study was to investigate the endometrial epithelial gene locus of the human hCG/LH gene cluster from CGB genes responsible for gene expression. For this study, endometrial specimens were selected from women characterized using our endometrium score and hCG staining index that had normal secretory transformed endometrium and optimal hCG staining. Using full-length CGB mRNA sequence analysis, we found that epithelial CGB is (co)expressed as the product of gene locus CGB7 and CGB6 (48%), as single CGB7 (42%), or to a lower percentage as single CGB6 (10%). In addition to known differences between these genes and CGB5, the nucleotide sequence of the mRNA differs between CGB7 and CGB6 in the untranslated promoter region and in translated exon 2. Immunohistochemical results show that endometrial joint CGB7 and CGB6, single CGB7, and single CGB6 mRNA expression lead to the release of endometrial hCG. Gene-specific antibodies for CGB7 reveal secretory endometrial hCG production, which is not observed for gene-specific CGB5 antibodies, whereas the placenta is positive for CGB5 and negative for CGB7 antibody as revealed by immunohistochemistry and Western blot hCG isoform analysis. Only endometrial CGB7 expression seems to be supported specifically by secretory endometrial transcription factors. In conclusion, epithelial hCG is expressed and produced as CGB7 and/or CGB6 but not CGB5, and it is produced together with CGA as a secretory transformation marker in the normal secretory phase endometrium.

Enhanced urothelial expression of human chorionic gonadotropin beta (hCGß) in bladder pain syndrome/interstitial cystitis (BPS/IC).

PURPOSE: Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGß with healthy controls. METHODS: Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGß and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGß expression was quantified. hCGß5 and hCGß7 mRNA splice variants were quantified in real-time polymerase chain reaction. RESULTS: We found constitutive expression of hCGα, hCGß and LHR in healthy controls. HCGß was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGß7 than hCGß5 in controls and BPS/IC patients. CONCLUSIONS: The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGß is upregulated in BPS/IC urothelium and that hCGß7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.

Treatment of Patients with Malignant Peritoneal Mesothelioma.

Malignant peritoneal mesothelioma is a rare malignancy arising from the serosa of the peritoneal cavity. It is diagnosed based on suspicious findings on cross sectional imaging and a tissue biopsy showing confirmatory histologic and immunohistochemical features. The disease is hallmarked by its propensity to progress mainly in the peritoneal cavity. In selected patients, surgical cytoreduction and hyperthermic intra-operative peritoneal chemotherapy has become the initial preferred treatment and is associated with provide prolonged in many patients. Systemic chemotherapy using a couplet of cisplatin or gemcitabine with pemetrexed has modest response rates and duration of response. Expression of PD-L1 has been demonstrated in peritoneal mesothelioma tumors and there has been significant interest in the use of check point blockade targeted against PD-L1 in this clinical setting. Future clinical research using a combination of check point blockade with surgical cytoreduction is a high clinical priority.

Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: effects on oxidative stress.

OBJECTIVE: To determine the effects of normoxic vs. hyperoxic resuscitation on oxidative stress in a model of pediatric asphyxial cardiac arrest. DESIGN: Prospective, interventional study. SETTING: University research laboratory. SUBJECTS: Postnatal day 16-18 rats (n = 5 per group). INTERVENTIONS: Rats underwent asphyxial cardiac arrest for 9 min. Rats were randomized to receive 100% oxygen, room air, or 100% oxygen with polynitroxyl albumin (10 mL·kg⁻¹ intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation. Shams recovered in 100% oxygen or room air after surgery. MEASUREMENTS AND MAIN RESULTS: Physiological variables were recorded at baseline to 1 hr after resuscitation. At 6 hrs after asphyxial cardiac arrest, levels of reduced glutathione and protein-thiols (fluorescent assay), activities of total superoxide dismutase and mitochondrial manganese superoxide dismutase (cytochrome c reduction method), manganese superoxide dismutase expression (Western blot), and lipid peroxidation (4-hydroxynonenal Michael adducts) were evaluated in brain tissue homogenates. Hippocampal 3-nitrotyrosine levels were determined by immunohistochemistry 72 hrs after asphyxial cardiac arrest. Survival did not differ among groups. At 1 hr after resuscitation, Pao2, pH, and mean arterial pressure were decreased in room air vs. 100% oxygen rats (59 ± 3 vs. 465 ± 46 mm Hg, 7.36 ± 0.05 vs. 7.42 ± 0.03, 35 ± 4 vs. 45 ± 5 mm Hg; p < .05). Rats resuscitated with 100% oxygen had decreased hippocampal reduced glutathione levels vs. sham (15.3 ± 0.4 vs. 20.9 ± 4.1 nmol·mg protein⁻¹; p < .01). Hippocampal manganese superoxide dismutase activity was significantly increased in 100% oxygen rats vs. sham (14 ± 2.4 vs. 9.5 ± 1.6 units·mg protein⁻¹, p < .01), with no difference in protein expression of manganese superoxide dismutase. Room air and 100% oxygen plus polynitroxyl albumin groups had hippocampal reduced glutathione and manganese superoxide dismutase activity levels comparable with sham. Protein thiol levels were unchanged across groups. Compared with all other groups, rats receiving 100% oxygen had increased immunopositivity for 3-nitrotyrosine in the hippocampus and increased lipid peroxidation in the cortex. CONCLUSIONS: Resuscitation with 100% oxygen leads to increased oxidative stress in a model that mimics pediatric cardiac arrest. This may be prevented by using room air or giving an antioxidant with 100% oxygen resuscitation.

Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy.

Regulatory T cells (Treg) expand during pregnancy and are present at the fetal-maternal interface at very early stages in pregnancy. The migration mechanisms of Treg to the pregnant uterus are still unclear. Human chorionic gonadotropin (hCG) is secreted by the blastocyst immediately after fertilization and has chemoattractant properties. Therefore, we sought to analyze whether hCG secreted by early trophoblasts attracts Treg to the uterus and hence contributes to maternal tolerance toward the fetus. Decidua and placenta tissue samples from patients having spontaneous abortions or ectopic pregnancies were employed to evaluate Treg and hCG levels. Age-matched samples from normal pregnant women served as controls. We further performed in vitro studies with primary first trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to evaluate the ability of secreted hCG to attract Treg. Patients having miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-beta mRNA levels as compared with normal pregnant women. Using migration assays we demonstrated that Treg were attracted by hCG-producing trophoblasts or choriocarcinoma cells. Treg migration toward cells transfected with hCG expression vectors confirmed the chemoattractant ability of hCG. Our data clearly show that hCG produced by trophoblasts attracts Treg to the fetal-maternal interface. High hCG levels at very early pregnancy stages ensure Treg to migrate to the site of contact between paternal Ags and maternal immune cells and to orchestrate immune tolerance toward the fetus.

[Fertility and cancer--outlining of the issue]. / Fertilität und Krebs--Skizzierung des Problemfeldes.

The subject "fertility and cancer" becomes increasingly important due to a steadily improving of survival rates of young patients. It is essential for patients being informed about possible consequences of their cancer disease and required medical care concerning a prospective parenthood. Any loss of fertility implies an additional devastating burden and rearrangement of the concept of life regarding to family planning. A transparent conversation about carefully considered treatment options of fertility preservation should be offered to the patients. Expertise on the part of oncologists about possible risks and a good physician-patient-communication are indispensable. Today fertility preserving strategies are available for females and males and could symbolise a bridge in the future. Prospective parenthood plays an important role for cancer patients. For using all opportunities of fertility preserving strategies offered to every patient, a close cooperation between oncologists and specialists in reproductive medicine is needed.