Neonatální infekce virem Herpes simplex (HSV) jsou vzácná, ale potenciálně smrtelná onemocnění. K přenosu infekce dochází nejčastěji během porodu, vzácněji postnatálně. Nejobávanější formou je diseminovaná infekce s multiorgánovým postižením, která je zatížena vysokou morbiditou a mortalitou. V tomto kazuistickém sdělení prezentujeme případ neočekávaného úmrtí novorozence, u kterého pitva odhalila diseminovanou infekci virem Herpes simplex 1 (HSV1).

Neonatal Herpes simplex virus (HSV) infections are rare but potentially fatal diseases. HSV infection is usually acquired when a newborn comes into contact with viable virus during intrapartum transit through infected birth canal. However, some cases are transmitted postnatally. Disseminated HSV infection with multiorgan involvement is the most feared form of the disease and is burdened with high morbidity and mortality. In this case report, we present a case of unexpected death of a neonate in whom the autopsy revealed disseminated Herpes simplex virus 1 (HSV1) infection.

• MeSH
• Liver diagnostic imaging   pathology   MeSH
• Humans MeSH
• Herpesvirus 1, Human * pathogenicity   MeSH
• Multiple Organ Failure diagnosis   etiology   pathology   MeSH
• Death, Sudden etiology   pathology   MeSH
• Infant, Newborn MeSH
• Perinatal Death * etiology   MeSH
• Autopsy methods   MeSH
• Lung diagnostic imaging   pathology   MeSH
• Polymerase Chain Reaction methods   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Case Reports MeSH

The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.

• MeSH
• Antiviral Agents pharmacology   therapeutic use   MeSH
• Flavonoids pharmacology   therapeutic use   MeSH
• Herpes Simplex * drug therapy   MeSH
• Humans MeSH
• Herpesvirus 1, Human * physiology   MeSH
• Life Cycle Stages MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Publikace se zaměřuje na diagnózu a terapii nemocí novorozenců. Určeno odborné veřejnosti.; Třetí vydání monografie našich předních specialistů v oboru je komplexním praktickým manuálem, který se snaží poskytnout ucelené informace o příčinách, symptomech a léčbě nejzávažnějších a nejčastějších patologických stavů novorozenců. Měl by pomoci v rychlé diagnostice problémů novorozence po porodu a v prvních dnech života, předložit širokou diferenciálnědiagnostickou rozvahu a přinést jasná aktuální doporučení vedoucí k léčbě dané patologie, ke stabilizaci stavu, případně připravit novorozence na transport. Kapitoly jsou uspořádány abecedně, každá odpovídá jednomu klinickému, laboratornímu nebo diagnostickému problému. Kromě aktualizace textů nového vydání byly doplněny a rozšířeny kapitoly z oblasti genetického vyšetřování a diagnostiky, chirurgické problematiky v neonatologii, oblasti neonatálních infekcí, podpůrné a paliativní péče a farmakologie v neonatologii. Publikace je určena pediatrům a neonatologům všech zdravotnických zařízení, především však lékařům menších a středních porodnic, novorozeneckých a dětských oddělení, kteří nemají široké zázemí jednotky intenzivní péče. Zároveň bude i cenným zdrojem odborných informací pro pregraduální a postgraduální studium a předatestační přípravu v pediatrii a neonatologii. První vydání publikace získalo cenu předsednictva České lékařské společnosti JEP za nejlepší odbornou knižní publikaci za rok 2013.

• MeSH
• Drug Therapy MeSH
• Neonatology MeSH
• Infant, Newborn MeSH
• Check Tag
• Infant, Newborn MeSH

• Conspectus
• Pediatrie
• NML Fields
• perinatologie a neonatologie
• NML Publication type
• kolektivní monografie

PURPOSE: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma. METHODS: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 106 plaque-forming unit (PFU) followed by ≤ 4 × 108 PFU 3 weeks later and once every 2 weeks until dose 5 and once every 3 weeks thereafter. Pembrolizumab was administered intravenously 200 mg once every 3 weeks. The dual primary end points were progression-free survival (PFS) per modified RECIST 1.1 by blinded independent central review and overall survival (OS). Secondary end points included objective response rate per mRECIST, CRR, and safety. Here, we report the primary analysis for PFS, the second preplanned interim analysis for OS, and the final analysis. RESULTS: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04; P = .13) or OS (hazard ratio, 0.96; 95% CI, 0.76 to 1.22; P = .74) compared with placebo-pembrolizumab. The objective response rate was 48.6% for T-VEC-pembrolizumab (CRR 17.9%) and 41.3% for placebo-pembrolizumab (CRR 11.6%); the durable response rate was 42.2% and 34.1% for the arms, respectively. Grade ≥ 3 treatment-related adverse events occurred in 20.7% of patients in the T-VEC-pembrolizumab arm and in 19.5% of patients in the placebo-pembrolizumab arm. CONCLUSION: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.

• MeSH
• Double-Blind Method MeSH
• Humans MeSH
• Herpesvirus 1, Human * MeSH
• Melanoma * drug therapy   MeSH
• Oncolytic Virotherapy * methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase I MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Antiviral Agents therapeutic use   MeSH
• Bacterial Infections drug therapy   MeSH
• Cellulite * diagnosis   etiology   drug therapy   MeSH
• Diagnostic Imaging MeSH
• Herpes Simplex drug therapy   complications   MeSH
• Conjunctivitis etiology   drug therapy   MeSH
• Humans MeSH
• Eyelids * microbiology   pathology   MeSH
• Oxacillin pharmacology   therapeutic use   MeSH
• Penicillin G pharmacology   therapeutic use   MeSH
• Child, Preschool * MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Child, Preschool * MeSH
• Publication type
• Case Reports MeSH

In last years, the decline of bacterial meningitides can be noticed. However, in the case of viral neuroinfections, the same trend is not observed. Although the most of viral meningitides have a benign course, they rang among severe diseases of childhood age. The reasons are, among others, prolonged hospitalization and the necessity of invasive diagnostic methods. The most frequent viral neuroinfections occurred in the Czech conditions are the tick-borne encephalitis and meningitides caused by enteroviruses and herpesviruses. The herpes simplex virus (HSV) and the varicella-zoster virus are the most important from the last group. There is a benefit of existing causal therapy of herpesviruses, however (especially in the case of HSV1 etiology) the results are unsatisfying and the prognosis remains grave. The standard diagnostic procedure is based on lumbar puncture and cerebrospinal fluid examination. The identification of etiology is recently much more accurate because of the extensive availability of polymerase chain reaction technique.

Současný ústup frekvence bakteriálních meningitid, ke kterému dochází v posledních letech, není patrný u virových neuroinfekcí. I když většina z nich má zpravidla benigní průběh, patří v dětském věku k obávaným onemocněním už proto, že jsou spojeny s poměrně dlouhou hospitalizací a invazivními diagnostickými metodami. V našich podmínkách se nejčastěji setkáváme se středoevropskou klíšťovou encefalitidou (tick-borne encephalitis, TBE), enterovirovými meningitidami a neuroinfekcemi způsobenými herpetickými viry, z nichž se uplatní zejména virus herpes simplex (HSV) a virus varicella-zoster (VZV). U posledně jmenovaných máme výhodu v možnosti kauzální terapie, ale zejména v případě encefalitidy etiologie HSV1 nejsou výsledky uspokojivé a prognóza zůstává velmi závažná. Základním diagnostickým postupem je lumbální punkce s vyšetřením likvoru, etiologická diagnostika se velmi zpřesnila s rozšířením dostupnosti identifikace etiologického agens pomocí polymerázové řetězové reakce (PCR).

• MeSH
• Child MeSH
• Encephalitis diagnosis   therapy   MeSH
• Central Nervous System Infections * diagnosis   etiology   therapy   MeSH
• Infant MeSH
• Humans MeSH
• Meningitis diagnosis   therapy   MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Humans MeSH
• Infant, Newborn, Diseases MeSH
• Infant, Newborn MeSH
• Virus Diseases * diagnosis   pathology   therapy   MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Review MeSH

• MeSH
• DNA, Viral isolation & purification   MeSH
• Herpesvirus 1, Human isolation & purification   MeSH
• Herpesvirus 2, Human isolation & purification   MeSH
• Reagent Kits, Diagnostic virology   MeSH
• Laboratory Proficiency Testing MeSH
• Herpesvirus 3, Human isolation & purification   MeSH

PURPOSE: Heterozygous mutations in CTLA4 lead to an inborn error of immunity characterized by immune dysregulation and immunodeficiency, known as CTLA-4 insufficiency. Cohort studies on CTLA4 mutation carriers showed a reduced penetrance (around 70%) and variable disease expressivity, suggesting the presence of modifying factors. It is well studied that infections can trigger autoimmunity in humans, especially in combination with a genetic predisposition. METHODS: To investigate whether specific infections or the presence of specific persisting pathogens are associated with disease onset or severity in CTLA-4 insufficiency, we have examined the humoral immune response in 13 CTLA4 mutation carriers, seven without clinical manifestation and six with autoimmune manifestations, but without immunoglobulin replacement therapy against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1/2 (HSV 1/2), parvovirus B19 and Toxoplasma gondii. Additionally, we have measured FcγRIII/CD16A activation by EBV-specific IgG antibodies to examine the functional capabilities of immunoglobulins produced by CTLA4 mutation carriers. RESULTS: The seroprevalence between affected and unaffected CTLA4 mutation carriers did not differ significantly for the examined pathogens. Additionally, we show here that CTLA4 mutation carriers produce EBV-specific IgG, which are unimpaired in activating FcγRIII/CD16A. CONCLUSIONS: Our results show that the investigated pathogens are very unlikely to trigger the disease onset in CTLA-4-insufficient individuals, and their prevalence is not correlated with disease severity or expressivity.

• MeSH
• CTLA-4 Antigen genetics   MeSH
• Immunoglobulin G MeSH
• Epstein-Barr Virus Infections * complications   epidemiology   MeSH
• Humans MeSH
• Antibodies, Viral MeSH
• Seroepidemiologic Studies MeSH
• Herpesvirus 4, Human * physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Long COVID, in which disease-related symptoms persist for months after recovery, has led to a revival of the discussion of whether neuropsychiatric long-term symptoms after viral infections indeed result from virulent activity or are purely psychological phenomena. In this review, we demonstrate that, despite showing differences in structure and targeting, many viruses have highly similar neuropsychiatric effects on the host. Herein, we compare severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus 1 (HIV-1), Ebola virus disease (EVD), and herpes simplex virus 1 (HSV-1). We provide evidence that the mutual symptoms of acute and long-term anxiety, depression and post-traumatic stress among these viral infections are likely to result from primary viral activity, thus suggesting that these viruses share neuroinvasive strategies in common. Moreover, it appears that secondary induced environmental stress can lead to the emergence of psychopathologies and increased susceptibility to viral (re)infection in infected individuals. We hypothesize that a positive feedback loop of virus-environment-reinforced systemic responses exists. It is surmised that this cycle of primary virulent activity and secondary stress-induced reactivation, may be detrimental to infected individuals by maintaining and reinforcing the host's immunocompromised state of chronic inflammation, immunological strain, and maladaptive central-nervous-system activity. We propose that this state can lead to perturbed cognitive processing and promote aversive learning, which may manifest as acute, long-term neuropsychiatric illness.

• Publication type
• Journal Article MeSH
• Review MeSH