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In this set of four phase 1 studies, a recombinant vesicular stomatitis virus (rVSV)–based Ebola vaccine induced Ebola virus–specific immune responses and was associated with side effects that included fever and transient arthritis, rash, and VSV viremia. In August 2014, after the outbreak of Ebola virus disease was declared a public health emergency of international concern by the World Health Organization (WHO), the Canadian government donated 800 vials of the replication-competent recombinant vesicular stomatitis virus (rVSV)–vectored Zaire ebolavirus (rVSV-ZEBOV) candidate vaccine to the WHO. The VSV Ebola Consortium (VEBCON) was created under the auspices of the WHO to initiate phase 1 studies to facilitate rapid progression to phase 2 and 3 trials in affected countries. 1 Live replicating viral vaccines elicit humoral and cellular immune responses against viral pathogens. 2 , 3 A single injection of 10 million plaque-forming units . . .

Background Single-incision laparoscopic surgery (SILS) has proved its advantages in several procedures, mainly a shorter hospital stay, improved aesthetic results, and less postoperative pain. The authors have used this approach for several thoracic surgical procedures. Methods This prospective study compared 20 cases between standard three-port video-assisted thoracic surgery (VATS) and the single-incision approach using a standard abdominal SILS system. In both groups, postsurgical analgesia was provided with 15 ml of bupivacaine 0.5% at 3 h intervals via a paravertebral catheter. The hospital length of stay and chest drain duration (in hours) were recorded as well as postoperative pain using an analogic visual pain scale (AVPS). A telephone survey was conducted for all the outpatients. The Mann-Whitney U test was used for statistical analysis. Results This study of 20 procedures included 11 lung biopsies, 6 pneumothorax procedures, 2 mediastinic cystectomies, and 1 catamenial pneumothorax procedure. No statistically significant difference was reported in hospital length of stay or chest drain duration between the two groups. However, postoperative pain at 24 h was significantly less in the SILS group (AVPS, 4.40) than in the VATS group (AVPS, 6.20) ( p  = 0.035). The SILS group reported two minor surgical wound complications and one catamenial pneumothorax recurrence that did not require drainage. The VATS group reported one case of skin rash with no identifiable cause. Conclusions The use of the SILS port in thoracic surgery results in less postoperative pain. This is related to the port’s protective effect over the periostium and the intercostal nerve, relieving them of direct contact with surgical instruments. However, the findings showed a higher incidence of surgical wound complications with the SILS port, which can be attributed to increased pressure on the skin and soft tissues surrounding the port and to the fact that this same incision was used for chest drain placement, thus increasing the risk for complications.

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25μg dose of parvovirus B19 recombinant capsid; 2.5 and 25μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5–9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important.

Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017–18 human monkeypox outbreak in Nigeria. We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. None.

This analysis investigates incidence and time course of rash in the EURTAC study. Patients with EGFR mutation-positive non-small-cell lung cancer were randomized 1:1 to receive once daily erlotinib or 3-weekly cycles of chemotherapy. Of the 86 erlotinib-treated patients, 71 reported rash. Median time to first rash appearance was 0.7 months. Most patients (n = 65) had the same or lower grade rash at final assessment compared with initial assessment. Of the 21 patients with decreased rash grade between initial and final assessments, 61.9% received no erlotinib dose modification, 42.8% had no concomitant rash treatment. Most rash cases were mild, occurred within 1 month of erlotinib treatment, and rapidly improved without the need for erlotinib dose alterations.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.

ObjectiveTo evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers.MethodsA web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included.Results136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss.ConclusionsPatients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.

A 31-year-old man was admitted with perianal and penile ulcers, rectal pain, and vesiculopustular rash. He had first noticed itchy white “bumps” around the anus 9 days earlier. A diagnostic test was performed.

ObjectiveLeukaemia is the most common cancer of childhood, accounting for a third of cases. In order to assist clinicians in its early detection, we systematically reviewed all existing data on its clinical presentation and estimated the frequency of signs and symptoms presenting at or prior to diagnosis.DesignWe searched MEDLINE and EMBASE for all studies describing presenting features of leukaemia in children (0–18 years) without date or language restriction, and, when appropriate, meta-analysed data from the included studies.ResultsWe screened 12 303 abstracts for eligibility and included 33 studies (n=3084) in the analysis. All were cohort studies without control groups. 95 presenting signs and symptoms were identified and ranked according to frequency. Five features were present in >50% of children: hepatomegaly (64%), splenomegaly (61%), pallor (54%), fever (53%) and bruising (52%). An additional eight features were present in a third to a half of children: recurrent infections (49%), fatigue (46%), limb pain (43%), hepatosplenomegaly (42%), bruising/petechiae (42%), lymphadenopathy (41%), bleeding tendency (38%) and rash (35%). 6% of children were asymptomatic on diagnosis.ConclusionsOver 50% of children with leukaemia have palpable livers, palpable spleens, pallor, fever or bruising on diagnosis. Abdominal symptoms such as anorexia, weight loss, abdominal pain and abdominal distension are common. Musculoskeletal symptoms such as limp and joint pain also feature prominently. Children with unexplained illness require a thorough history and focused clinical examination, which should include abdominal palpation, palpation for lymphadenopathy and careful scrutiny of the skin. Occurrence of multiple symptoms and signs should alert clinicians to possible leukaemia.