Role of the Binding Energy on Nondipole Effects in Single-Photon Ionization.

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

TSPO PET, tumour grading and molecular genetics in histologically verified glioma: a correlative 18F-GE-180 PET study.

BACKGROUND: The 18-kDa translocator protein (TSPO) is overexpressed in brain tumours and represents an interesting target for glioma imaging. 18F-GE-180, a novel TSPO ligand, has shown improved binding affinity and a high target-to-background contrast in patients with glioblastoma. However, the association of uptake characteristics on TSPO PET using 18F-GE-180 with the histological WHO grade and molecular genetic features so far remains unknown and was evaluated in the current study. METHODS: Fifty-eight patients with histologically validated glioma at initial diagnosis or recurrence were included. All patients underwent 18F-GE-180 PET, and the maximal and mean tumour-to-background ratios (TBRmax, TBRmean) as well as the PET volume were assessed. On MRI, presence/absence of contrast enhancement was evaluated. Imaging characteristics were correlated with neuropathological parameters (i.e. WHO grade, isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and telomerase reverse transcriptase (TERT) promoter mutation). RESULTS: Six of 58 patients presented with WHO grade II, 16/58 grade III and 36/58 grade IV gliomas. An (IDH) mutation was found in 19/58 cases, and 39/58 were classified as IDH-wild type. High 18F-GE-180-uptake was observed in all but 4 cases (being WHO grade II glioma, IDH-mutant). A high association of 18F-GE-180-uptake and WHO grades was seen: WHO grade IV gliomas showed the highest uptake intensity compared with grades III and II gliomas (median TBRmax 5.15 (2.59-8.95) vs. 3.63 (1.85-7.64) vs. 1.63 (1.50-3.43), p < 0.001); this association with WHO grades persisted within the IDH-wild-type and IDH-mutant subgroup analyses (p < 0.05). Uptake intensity was also associated with the IDH mutational status with a trend towards higher 18F-GE-180-uptake in IDH-wild-type gliomas in the overall group (median TBRmax 4.67 (1.56-8.95) vs. 3.60 (1.50-7.64), p = 0.083); however, within each WHO grade, no differences were found (e.g. median TBRmax in WHO grade III glioma 4.05 (1.85-5.39) vs. 3.36 (2.32-7.64), p = 1.000). No association was found between uptake intensity and MGMT or TERT (p > 0.05 each). CONCLUSION: Uptake characteristics on 18F-GE-180 PET are highly associated with the histological WHO grades, with the highest 18F-GE-180 uptake in WHO grade IV glioblastomas and a PET-positive rate of 100% among the investigated high-grade gliomas. Conversely, all TSPO-negative cases were WHO grade II gliomas. The observed association of 18F-GE-180 uptake and the IDH mutational status seems to be related to the high inter-correlation of the IDH mutational status and the WHO grades.

Outcomes of octogenarians with esophageal cancer: an analysis of the National Cancer Database.

The optimal treatment of esophageal cancer in octogenarians is controversial. While the safety of esophagectomy has been demonstrated in elderly patients, surgery and multimodality therapy are still offered to a select group. Additionally, the long-term outcomes in octogenarians have not been thoroughly compared to those in younger patients. We sought to compare the outcomes of esophageal cancer treatment between octogenarians and non-octogenarians in the National Cancer Database (2004-2014). The major endpoints were early postoperative mortality and long-term survival. A total of 107,921 patients were identified [octogenarian-16,388 (15.2%)]. Compared to non-octogenarians, octogenarians were more likely to be female, of higher socioeconomic status, and had more Charlson comorbidities (p < 0.001 for all). Octogenarians were significantly less likely to undergo esophagectomy (11.5% vs. 33.3%; p < 0.001) and multimodality therapy (2.0% vs. 18.5%; p < 0.001), a trend that persisted following stratification by tumor stage and Charlson comorbidities. Both 30-day and 90-day mortality were higher in the octogenarian group, even after multivariable adjustment (p ≤ 0.001 for both). Octogenarians who underwent multimodality therapy had worse long-term survival when compared to younger patients, except for those with stage III tumors and no comorbidities (HR: 1.29; p = 0.153). Within the octogenarian group, postoperative mortality was lower in academic centers, and the long-term survival was similar between multimodality treatment and surgery alone (HR: 0.96; p = 0.62). In conclusion, octogenarians are less likely to be offered treatment irrespective of tumor stage or comorbidities. Although octogenarians have higher early mortality and poorer overall survival compared to younger patients, outcomes may be improved when treatment is performed at academic centers. Multimodality treatment did not seem to confer a survival advantage compared to surgery alone in octogenarians, and more prospective studies are necessary to better elucidate the optimal treatment in this patient population.

Relationship between oviposition, virulence gene expression and parasitism success in Cotesia typhae nov. sp. parasitoid strains.

Studying mechanisms that drive host adaptation in parasitoids is crucial for the efficient use of parasitoids in biocontrol programs. Cotesia typhae nov. sp. (Fernández-Triana) (Hymenoptera: Braconidae) is a newly described parasitoid of the Mediterranean corn borer Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae). Braconidae are known for their domesticated bracovirus, which is injected with eggs in the host larva to overcome its resistance. In this context, we compared reproductive success traits of four Kenyan strains of C. typhae on a French and a Kenyan populations of its host. Differences were found between the four strains and the two most contrasted ones were studied more thoroughly on the French host population. Parasitoid offspring size was correlated with parasitism success and the expression of bracovirus virulence genes (CrV1 and Cystatin) in the host larva after parasitism. Hybrids between these two parasitoid strains showed phenotype and gene expression profiles similar to the most successful parental strain, suggesting the involvement of dominant alleles in the reproductive traits. Ovary dissections revealed that the most successful strain injected more eggs in a single host larva than the less successful one, despite an equal initial ovocyte number in ovaries. It can be expected that the amount of viral particles increase with the number of eggs injected. The ability to bypass the resistance of the allopatric host may in consequence be related to the oviposition behaviour (eggs allocation). The influence of the number of injected eggs on parasitism success and on virulence gene expression was evaluated by oviposition interruption experiments.

The Cotesia sesamiae story: insight into host-range evolution in a Hymenoptera parasitoid and implication for its use in biological control programs.

This review covers nearly 20 years of studies on the ecology, physiology and genetics of the Hymenoptera Cotesia sesamiae, an African parasitoid of Lepidoptera that reduces populations of common maize borers in East and South Africa. The first part of the review presents studies based on sampling of C. sesamiae from maize crops in Kenya. From this agrosystem including one host plant and three main host borer species, studies revealed two genetically differentiated populations of C. sesamiae species adapted to their local host community, and showed that their differentiation involved the joint evolution of virulence genes and sensory mechanisms of host acceptance, reinforced by reproductive incompatibility due to Wolbachia infection status and natural inbreeding. In the second part, we consider the larger ecosystem of wild Poales plant species hosting many Lepidoptera stem borer species that are potential hosts for C. sesamiae. The hypothesis of other host-adapted C. sesamiae populations was investigated based on a large sampling of stem borer larvae on various Poales across sub-Saharan Africa. The sampling provided information on the respective contribution of local hosts, biogeography and Wolbachia in the genetic structure of C. sesamiae populations. Molecular evolution analyses highlighted that several bracovirus genes were under positive selection, some of them being under different selection pressure in C. sesamiae populations adapted to different hosts. This suggests that C. sesamiae host races result from co-evolution acting at the local scale on different bracovirus genes. The third part considers the mechanisms driving specialization. C. sesamiae host races are more or less host-specialized. This character is crucial for efficient and environmentally-safe use of natural enemies for biological control of pests. One method to get an insight in the evolutionary stability of host-parasite associations is to characterize the phylogenetic relationships between the so-called host-races. Based on the construction of a phylogeny of C. sesamiae samples from various host- and plant species, we revealed three main lineages. Mechanisms of differentiation are discussed with regard to the geography and ecology of the samples. One of the lineage presented all the hallmarks of a distinct species, which has been morphologically described and is now studied in the perspective of being used as biological control agent against Sesamia nonagrioides Lefèbvre (Lepidoptera: Noctuidae), a major maize pest in West Africa and Mediterranean countries (see Benoist et al. 2017). The fourth part reviews past and present use of C. sesamiae in biological control, and points out the interest of such molecular ecology studies to reconcile biodiversity and food security stakes in future biological control.

Azadirachtin impact on mate choice, female sexual receptivity and male activity in Drosophila melanogaster (Diptera: Drosophilidae).

Azadirachtin, a neem compound (Azadirachta indica) with medical and anti-insect properties, is one the most successful botanical pesticides in agricultural use. However, its controversial impact on non-targeted species and its mechanism of action need to be clarified. In addition, Azadirachtin impact on pre- and post-mating traits remains largely undocumented. The current study examined the effects of Azadirachtin on Drosophila melanogaster as a non-target and model species. Azadirachtin was applied topically at its LD50 (0.63µg) on the day of adult emergence and its effect was evaluated on several traits of reproductive behavior: mate choice, male activity, female sexual receptivity, sperm storage and female sterility. In choice and no choice conditions, only male treatment reduced mating probability. Female treatment impaired mating probability only when males had the choice. Males' mating ability may have been impaired by an effect of the treatment on their mobility. Such an effect was observed in the actimeter, which revealed that treated males were less active than untreated ones, and this effect persisted over 8days. Azadirachtin treatment had, however, no effect on the nycthemeral rhythm of those males. Even when mating occurred, Azadirachtin treatment impaired post-mating responses especially when females or both sexes were treated: remating probability increases and female fertility (presence of larvae) decreases. No impairment was observed on the efficiency of mating, evaluated by the presence of sperm in the spermatheca or the ventral receptacle. Male treatment only had no significant effect on these post-mating responses. These findings provide clear evidence that Azadirachtin alters the reproductive behavior of both sexes in D. melanogaster via mating and post-mating processes.

[Health-related quality of life after mechanical ventilation in the intensive care unit]. / Gesundheitsbezogene Lebensqualität nach Beatmung auf der Intensivstation.

BACKGROUND: It is unknown whether health related quality of life measured in German patients one year after mechanical ventilation in the intensive care unit is impaired or not. OBJECTIVES: The aim of this study was to assess health related quality of life one year after inclusion into a randomized controlled trial for weaning from mechanical ventilation with the help of a questionnaire that has never been used in critically ill patients and to investigate whether health related quality of life scores differ between the study population and a general German population. METHODS: We followed up with patients one year after inclusion into a randomized control trial investigating the effect of SmartCare/PS on total ventilation time compared to protocol-driven weaning (ASOPI trial, clinicaltrials.gov ID00445289). Health related quality of life was measured using the quality of life questionnaire C­30 version 3.0 from the European Organization of Research and Treatment of Cancer (EORTC). Mean differences of at least 10 score points in the quality of life scales were considered clinically significant. RESULTS: Of the 232 patients who were alive 90 days after study inclusion, 24 patients died one year after study inclusion and 64 patients were lost to follow-up. Of the remaining145 patients who were successfully contacted, 126 patients agreed to fill out the questionnaire. Questionnaires were sent back to the study site by 83 patients and these were analyzed. Health-related quality of life was significantly lower in five of the six functional scales (physical functioning, role functioning, cognitive functioning, social functioning, global health status) and in eight of the nine symptom scales (fatigue, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) compared to the reference values of a German normal population. CONCLUSIONS: The EORTC QLQ-C30 questionnaire is suitable for the acquisition of the health-related quality of life in formerly critically ill patients. Health-related quality of life is severely impaired after mechanical ventilation in the intensive care unit. Future studies should consider health related quality of life as a possible study endpoint.

Long-term, high-level hepatic secretion of acid α-glucosidase for Pompe disease achieved in non-human primates using helper-dependent adenovirus.

Pompe disease (glycogen storage disease type II (GSD-II)) is a myopathy caused by a genetic deficiency of acid α-glucosidase (GAA) leading to lysosomal glycogen accumulation causing muscle weakness, respiratory insufficiency and death. We previously demonstrated in GSD-II mice that a single injection of a helper-dependent adenovirus (HD-Ad) expressing GAA resulted in at least 300 days of liver secretion of GAA, correction of the glycogen storage in cardiac and skeletal muscles and improved muscle strength. Recent reports suggest that gene therapy modeling for lysososomal storage diseases in mice fails to predict outcomes in larger animal models. We therefore evaluated an HD-Ad expressing GAA in non-human primates. The baboons not only tolerated the procedure well, but the results also confirmed that a single dose of the HD-Ad allowed the livers of the treated animals to express and secrete large amounts of GAA for at least 6 months, at levels similar to those achieved in mice. Moreover, we detected liver-derived GAA in the heart, diaphragm and skeletal muscles of the treated animals for the duration of the study at levels that corrected glycogen accumulation in mice. This work validates our proof-of-concept studies in mice, and justifies future efforts using Ad-based vectors in Pompe disease patients.

Emergence of Acquired HIV-1 Drug Resistance Almost Stopped in Switzerland: A 15-Year Prospective Cohort Analysis.

BACKGROUND: Drug resistance is a major barrier to successful antiretroviral treatment (ART). Therefore, it is important to monitor time trends at a population level. METHODS: We included 11 084 ART-experienced patients from the Swiss HIV Cohort Study (SHCS) between 1999 and 2013. The SHCS is highly representative and includes 72% of patients receiving ART in Switzerland. Drug resistance was defined as the presence of ≥1 major mutation in a genotypic resistance test. To estimate the prevalence of drug resistance, data for patients with no resistance test was imputed based on the patient's risk of harboring drug-resistant viruses. RESULTS: The emergence of new drug resistance mutations declined dramatically from 401 to 23 patients between 1999 and 2013. The upper estimated prevalence limit of drug resistance among ART-experienced patients decreased from 57.0% in 1999 to 37.1% in 2013. The prevalence of 3-class resistance decreased from 9.0% to 4.4% and was always <0.4% for patients who initiated ART after 2006. Most patients actively participating in the SHCS in 2013 with drug-resistant viruses initiated ART before 1999 (59.8%). Nevertheless, in 2013, 94.5% of patients who initiated ART before 1999 had good remaining treatment options based on Stanford algorithm. CONCLUSIONS: Human immunodeficiency virus type 1 drug resistance among ART-experienced patients in Switzerland is a well-controlled relic from the era before combination ART. Emergence of drug resistance can be virtually stopped with new potent therapies and close monitoring.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND: Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS: A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS: Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS: We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

[Reemergence of Chikungunya virus]. / Chikungunya: La reemergence.

Arboviral diseases transmitted by mosquitoes such as Dengue, Chikungunya and West Nile are global health issues of growing magnitude. Their dissemination in new areas is triggered by increased mobility of persons, animal reservoirs and vectors. This article describes virological, epidemiological and clinical aspects of Chikungunya, which causes sporadic cases or epidemics, sometimes massive, such as the one spreading in the Americas since December 2013. Chikungunya should be suspected in all travellers presenting with fever, arthralgia and sometimes a rash returning from an endemic area. In the absence of vaccine, individual protection relies on the prevention of mosquito bites.

[Ebola: the unexpected emerging disease]. / Ebola: le point au crépuscule d'une épidémie inattendue.

In one year, Ebola virus disease has already been responsible of around 10000 deaths. 24 patients have been medically evacuated in different University Hospitals in Europe or in the United States. One medical doctor, infected during a humanitarian mission in the field has been treated in Geneva at the end of 2014. This review aims to summarize the epidemiology of the current outbreak, to describe the main virological and clinical characteristics of Ebola virus disease, and to address the most important experimental treatments available. Although the number of cases has fallen the last two months, the outbreak is not over. A safe and proctective vaccine is still needed in the race to fight this emerging viral disease.

[New viruses: myth, fantasy or reality?]. / Nouveaux virus: mythe, fantasme ou réalité?

Emerging viruses previously unknown or partially known that infect repeatedly the human population are more than ever in the medias actuality headlines. Multiple factors may explain this dynamic. The most important is certainly the rapid evolution and the adaptation capacity of these viruses. Note that the increase in travel and international trade or climate change also play an important role. On the other hand, laboratory tests and current surveillance systems are more efficient. Thus, transmission of virus from an animal reservoir to human are more easily detected, accentuating the feeling of increasing phenomenon. Virological predictions have very low reliability in epidemiology. It is a reality that we have to accept.

CDK9 inhibition as an effective therapy for small cell lung cancer.

Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance to first-line therapy and alternative therapies are urgently required to overcome this resistance. In this study, we tested the efficacy of dinaciclib, an FDA-orphan drug and inhibitor of the cyclin-dependent kinase (CDK) 9, among other CDKs, in SCLC. Furthermore, we report on a newly developed, highly specific CDK9 inhibitor, VC-1, with tumour-killing activity in SCLC. CDK9 inhibition displayed high killing potential in a panel of mouse and human SCLC cell lines. Mechanistically, CDK9 inhibition led to a reduction in MCL-1 and cFLIP anti-apoptotic proteins and killed cells, almost exclusively, by intrinsic apoptosis. While CDK9 inhibition did not synergise with chemotherapy, it displayed high efficacy in chemotherapy-resistant cells. In vivo, CDK9 inhibition effectively reduced tumour growth and improved survival in both autochthonous and syngeneic SCLC models. Together, this study shows that CDK9 inhibition is a promising therapeutic agent against SCLC and could be applied to chemo-refractory or resistant SCLC.

Family outbreak of an infection with a recombinant Coxsackie A virus in eastern Switzerland.

PURPOSE: We report on an unusual familial outbreak of a coxsackie virus infection in Switzerland in which five family members were affected. Most of the patients presented with signs of meningitis, and four were hospitalized. METHODS: In three individuals, the virus was detected in the cerebrospinal fluid, pharynx, and stool, respectively. The genome was sequenced in specimens of two patients. RESULTS: The nucleotide sequences of both virus strains were identical. Blast search revealed that the first half of the sequence was 88 % homologous to Enterovirus 75 (EV-75), 87 % with Echovirus 11 (E-11), and 84 % homologous to Coxsackie virus A9 (CV-A9). The second half of the sequence was 77 % homologous to EV-75, 75 % to E-11, and 91 % to CV-A9. CONCLUSION: We propose that the isolated virus strain is a recombinant strain with a 5' untranslated region and with the start of the VP4 sequence originating from E-11/EV-75 and the rest of the genome originating from CV-A9. Interestingly, this novel virus strain showed an exceptional virulence and rapid spread. Two weeks after the initial outbreak in this family, a similar outbreak was observed in a second geographic area roughly 100 km distant to the primary identification site, and another 2 months later this virus strain was found to circulate in the western part of Switzerland some 250 km distant to the primary locus. These findings suggest that genetic recombination has resulted in a novel enterovirus with features of high virulence, contagiosity, and spreading.

Rational Use of Microbiological Tests in the Diagnosis of Central Nervous System Infections Using Restrictive Criteria: a Retrospective Study.

Central nervous infections, mostly represented by meningitis and encephalitis, remain a diagnostic challenge despite substantial advances in microbiological tools in recent years. Meanwhile, extensive microbiological workups, which often prove to be irrelevant retrospectively, continue to be processed on a large scale, therefore leading to unnecessary costs. The main goal of this study was to evaluate a systematic approach enabling more rational use of microbiological tools in the setting of community-acquired central nervous system infection diagnosis. In this single-center descriptive study, the modified Reller criteria were retrospectively extended to all neuropathogens tested in cerebrospinal fluid (CSF) samples with the FilmArray meningitis/encephalitis panel (BioFire Diagnostics, LLC) and bacterial culture. The inclusion period was 30 months. In total, 1,714 fluid (CSF) samples analyzed from 1,665 patients over 2 and a half years were reported. According to the retrospective application of the modified Reller criteria, microbiological testing was considered unnecessary in 544 CSF samples. Fifteen positive microbiological results were found among these samples, interpreted either as inherited chromosomally integrated human herpesvirus 6 (HHV-6), a false-positive result, or a true microbial detection without clinical relevance. No CNS infection case would have been missed if these analyses were not carried out, while about one-third of all meningitis/encephalitis multiplex PCR panels would have been saved. Our retrospective analysis suggests that the modified Reller criteria could be safely applied to all microbiological tests performed in CSF, thereby saving substantial costs. IMPORTANCE Microbiological testing in general and in the setting of central nervous system (CNS) infection in particular are often excessive, leading to superfluous laboratory work and costs. In this regard, restrictive criteria, named Reller criteria, have been developed to reduce unnecessary CSF herpes simplex virus 1 (HSV-1) PCR testing when suspecting encephalitis. These criteria were then adapted for increased safety to become the modified Reller criteria. This retrospective study aims at evaluating the safety of these criteria when applied to CSF microbiological testing in general, including multiplex PCR, direct examination, and bacterial culture. The postulate was that a CNS infection can be excluded if none of these criteria is present. According to our data set, no CNS infection would have been missed if the modified Reller criteria would have been applied to save microbiological tests. This study therefore proposes a simple way to reduce unnecessary microbiological testing in the context of CNS infection suspicion.