Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany.

BACKGROUND: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. METHODS: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). RESULTS: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. CONCLUSIONS: In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

Intraoperative conversion and complications in robotic assisted primary and redo gastric bypass surgery.

The rise of robotic assisted surgery in the treatment of morbidly obese patients has enlarged the armamentarium for surgeons involved in bariatric surgery. This in particular is of great advantage not only in primary cases, but also in patients undergoing revisional procedures following preceding upper GI surgery. In the following, our experience with intraoperative conversions and complications in revisional robotic surgery using the Da Vinci robotic system will be reported and compared to primary robotic bypass surgery and the literature. In a 36-month period, a total of 157 minimally invasive bariatric procedures (48 robotic assisted, 109 laparoscopic) were performed. Out of 43 patients receiving a gastric bypass 32 (74%) were performed robotically. Out of these 20 (62.5%) had previous operations (RRBP): one hiatal mesh repair, one open Mason operation, eight gastric band, nine gastric sleeve, one sleeve with fundoplication. The Da Vinci Xi was used for all surgeries. 3/20 (15%) RRBP were converted to open laparotomy because of a huge left liver lobe (1), extreme adhesions (1) and short mesentery (1) (p = 0.631 vs 1/12 RBP). One out of these had to be reoperated for an insufficiency of the gastroenterostomy. 3/17 (23%) patients (RRBP) without conversion had complications: hemorrhage (1), insufficiency of biliodigestive anastomosis (1), insufficiency of gastroenterostomy (1). There was no mortality and length of hospital stay was 3.5 days in uncomplicated cases and 12.3 days in complicated cases (p < 0.05). This preliminary experience suggests, that robotic revisional surgery can be performed safely even in complicated cases. Conversion to laparoscopic or open surgery may be required when adverse anatomical conditions are present. However, the incidence of complications was not increased when conversion was performed. In this series, the incidence of complications was not greater in case of revisional surgery.

Effective Halogen-Free Flame-Retardant Additives for Crosslinked Rigid Polyisocyanurate Foams: Comparison of Chemical Structures.

The impact of phosphorus-containing flame retardants (FR) on rigid polyisocyanurate (PIR) foams is studied by systematic variation of the chemical structure of the FR, including non-NCO-reactive and NCO-reactive dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO)- and 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-containing compounds, among them a number of compounds not reported so far. These PIR foams are compared with PIR foams without FR and with standard FRs with respect to foam properties, thermal decomposition, and fire behavior. Although BPPO and DOPO differ by just one oxygen atom, the impact on the FR properties is very significant: when the FR is a filler or a dangling (dead) end in the PIR polymer network, DOPO is more effective than BPPO. When the FR is a subunit of a diol and it is fully incorporated in the PIR network, BPPO delivers superior results.

Minimally Invasive Conversion of a Gastric Bypass into Sleeve Gastrectomy for Postprandial Hyperinsulinemic Hypoglycemia.

The treatment of postprandial hyperinsulinemic hypoglycemia following gastric bypass surgery for obesity can be challenging despite dietetic and medical treatment and eventually surgical treatment remains the exclusive treatment to resolve the problem for the patient. In the following, the experience with a conversion surgery from a complicated Roux-en-Y gastric bypass to sleeve gastrectomy using the Da Vinci robotic system will be reported.

Improving the Flame Retardance of Polyisocyanurate Foams by Dibenzo[d,f][1,3,2]dioxaphosphepine 6-Oxide-Containing Additives.

A series of new flame retardants (FR) based on dibenzo[d,f][1,3,2]dioxaphosphepine 6-oxide (BPPO) incorporating acrylates and benzoquinone were developed previously. In this study, we examine the fire behavior of the new flame retardants in polyisocyanurate (PIR) foams. The foam characteristics, thermal decomposition, and fire behavior are investigated. The fire properties of the foams containing BPPO-based derivatives were found to depend on the chemical structure of the substituents. We also compare our results to state-of-the-art non-halogenated FR such as triphenylphosphate and chemically similar phosphinate, i.e. 9,10-dihydro-9-oxa-10- phosphaphenanthrene-10-oxide (DOPO), based derivatives to discuss the role of the phosphorus oxidation state.

Virucidal efficacy of peracetic acid for instrument disinfection.

BACKGROUND: Various peracetic-acid (PAA)-based products for processing flexible endoscopes on the market are often based on a two-component system including a cleaning step before the addition of PAA as disinfectant. The peracetic acid concentrations in these formulations from different manufacturers are ranging from 400 to 1500 ppm (part per million). These products are used at temperatures between 20 °C and 37 °C. Since information on the virus-inactivating properties of peracetic acid at different concentrations and temperature is missing, it was the aim of the study to evaluate peracetic acid solutions against test viruses using the quantitative suspension test, EN 14476. In addition, further studies were performed with the recently established European pre norm (prEN 17111:2017) describing a carrier assay for simulating practical conditions using frosted glass. METHODS: In the first step of examination, different PAA solutions between 400 and 1500 ppm were tested at 20 °C, 25 °C, and 35 °C with three test viruses (adenovirus, murine norovirus and poliovirus) necessary for creating a virucidal action according to the European Norm, EN 14476. A second step for simulating practical conditions based on prEN 17111:2017 followed by spreading a test virus together with soil load onto a glass carrier which was immerged into a peracetic acid solution. A fixed exposure time of five minutes was used in all experiments. RESULTS: In the quantitative suspension test 1500 ppm PAA solution was needed at 35 °C for five minutes for the inactivation of poliovirus, whereas only 400 ppm at 20 °C for adeno- and murine norovirus were necessary. In the carrier assay 400 ppm peracetic acid at 20 °C were sufficient for adenovirus inactivation, whereas 600 ppm PAA were needed at 25 °C and 35 °C and 1000 ppm at 20 °C for murine norovirus. A PAA solution with 1000 ppm at 35 °C was required for complete inactivation of poliovirus. However, a dramatically decrease of titer after the drying and immerging could be observed. In consequence, a four log reduction of poliovirus titer could not be achieved in the carrier test. CONCLUSION: In summary, 1500 ppm PAA at 35 °C was necessary for a virucidal action in the quantitative suspension test. After passing the requirements of the suspension test, additional examinations with adeno- and murine norovirus on glass carriers based on prEN 17111:2017 will not additionally contribute to the final claim of an instrument disinfectant for virucidal efficacy. This is due to the great stability of poliovirus in the preceded quantitative suspension test and the fact that poliovirus could not serve as test virus in the following carrier assay.

Detection of HBoV DNA in idiopathic lung fibrosis, Cologne, Germany.

We report two confirmed cases of usual interstitial pneumonia (UIP) associated with infection of the human bocavirus (HBoV). In one case HBoV was identified in the bronchoalveolar lavage (BAL) during an acute exacerbation as well as post mortem in different tissues giving raise to the hypothesis that HBoV infections trigger UIP or could be a causative agent and be a systemic component in UIP. In the other case, the UIP was confirmed by radiological methods and HBoV was detected in the BAL during an acute exacerbation. Both cases give raise to the hypothesis that HBoV could be a causative agent of UIP or could contribute to its development and/or acute exacerbations.

S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.

INTRODUCTION: The recent introduction of integrase inhibitors (INIs) into the HIV treatment armentarium has had a significant impact on HIV treatment. However, at present, raltegravir twice daily is the only licensed INI featuring a lower genetic barrier compared with boosted protease inhibitors. S/GSK1349572 represents a new INI in current development. It is a once-daily, unboosted INI with low pharmacokinetic variability and predictable exposure-response relationship. Phase IIb studies in antiretroviral-naïve patients have demonstrated non-inferiority to efavirenz-based HIV therapy. Phase II studies in INI-experienced patients show partially retained activity in vivo. Overall, the safety profile of S/GSK1349572 in all studies completed has been very favorable. AREAS COVERED: A Pubmed and Medline search was carried out on all articles on S/GSK1349572 from 2005 to 2010, including recent abstract presentations from major HIV conferences (CROI 2010, WAC2010, EACS2009, HIV10 and ICAAC2010). The reader will become acquainted with the unique properties of this new INI and will understand the current promises and challenges of the data available from S/GSK1349572. EXPERT OPINION: S/GSK1349572 represents a new, unboosted, once-daily INI in development with distinct pharmacokinetics and resistance profile, which has showed promising potency and tolerability in the first clinical studies.

Vicriviroc, a new CC-chemokine receptor 5 inhibitor for treatment of HIV: properties, promises and challenges.

IMPORTANCE OF THE FIELD: Although HIV has become a treatable disease with near to normal life expectancy, the quest for the development of better tolerated drugs with simple dosing schedules and a high barrier to the emergence of drug resistance remains. Vicriviroc is a small-molecule chemokine receptor antagonist that inhibits the binding of R5-tropic HIV-1 to host cells at the CC-chemokine receptor 5 (CCR5) co-receptor, thus, preventing viral entry. CCR5 inhibitors are believed to possibly decrease inflammation from the immune system and thereby offer additional properties further to their antiretroviral efficacy. AREAS COVERED IN THIS REVIEW: This review is based on a PubMed search covering the years 2005 - 2010 for pharmacokinetic, pharmacological and clinical data of vicriviroc. WHAT THE READER WILL GAIN: In this review, the pharmacokinetic, pharmacological and clinical data of vicriviroc are presented. Moreover, the potential role of vicriviroc in the growing HIV armamentarium is discussed. TAKE HOME MESSAGE: Vicriviroc is being developed to be administered in combination with a ritonavir-boosted protease inhibitor for patients with R5-tropic virus. Early clinical trials have established the safety of vicriviroc in both treatment-naive and -experienced R5-tropic HIV-1 infected individuals. Recently, two Phase III clinical trials in treatment-experienced patients failed to prove its superiority over available HIV medications. Phase III trials for treatment-naive patients are still under planning. Clearly, more favorable study results are needed to move vicriviroc into drug registration and approval.

Long-term effects of disinfectants on the community composition of drinking water biofilms.

Numerous investigations have demonstrated efficiencies of different disinfection methods, but until now only little is known about long-term effects on community compositions of drinking water biofilms. Changes in the community structure, especially regrowth of hygienically relevant microorganisms could be critical for the drinking water quality. In this study the long-term effect of disinfection methods on biofilm communities in drinking water systems was analysed. Old drinking water biofilms grown in silicone tubes were exposed to different preparations of disinfectants (free chlorine, chlorine dioxide, hydrogen peroxide combined with fruit acid, silver and silver with peracetic acid, respectively) and subsequently further exposed in the original drinking water. The comparison of the treated and regrown biofilm populations with untreated ones by the DNA-fingerprinting method denaturing gradient gel electrophoresis (DGGE) revealed a considerable population shift caused by the disinfectants. The disinfection methods induced a selection pressure on the biofilm populations depending on the composition and concentrations. The similarities between the treated and untreated biofilms were generally low. Compared to preparations with peracetic acid the disinfection with hydrogen peroxide and silver resulted in higher similarities of the treated and untreated biofilms, but the microbial diversity increased. It can be concluded that the disinfectants have a major impact on the drinking water biofilm communities and that possibly the intervention selects persisters and microorganisms, which can live on the residuals of the dead biofilm cells. For the evaluation of the efficiency of disinfection methods in drinking water installations it is necessary not only to consider reduction of certain bacteria but also to pay attention to the biofilm community.

Ca2+-controlled competitive diacylglycerol binding of protein kinase C isoenzymes in living cells.

The cellular decoding of receptor-induced signaling is based in part on the spatiotemporal activation pattern of PKC isoforms. Because classical and novel PKC isoforms contain diacylglycerol (DAG)-binding C1 domains, they may compete for DAG binding. We reasoned that a Ca2+-induced membrane association of classical PKCs may accelerate the DAG binding and thereby prevent translocation of novel PKCs. Simultaneous imaging of fluorescent PKC fusion proteins revealed that during receptor stimulation, PKC alpha accumulated in the plasma membrane with a diffusion-limited kinetic, whereas translocation of PKC epsilon was delayed and attenuated. In BAPTA-loaded cells, however, a selective translocation of PKC epsilon, but not of coexpressed PKC alpha, was evident. A membrane-permeable DAG analogue displayed a higher binding affinity for PKC epsilon than for PKC alpha. Subsequent photolysis of caged Ca2+ immediately recruited PKC alpha to the membrane, and DAG-bound PKC epsilon was displaced. At low expression levels of PKC epsilon, PKC alpha concentration dependently prevented the PKC epsilon translocation with half-maximal effects at equimolar coexpression. Furthermore, translocation of endogenous PKCs in vascular smooth muscle cells corroborated the model that a competition between PKC isoforms for DAG binding occurs at native expression levels. We conclude that Ca2+-controlled competitive DAG binding contributes to the selective recruitment of PKC isoforms after receptor activation.