Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

In vitro C3 mRNA expression is pemphigus vulgaris: Complement activation is increased by IL-1α and TNF-α

Background: Pemphigus vulgaris (PV) is a potentially life-threatening disease, characterized immunohistologically by IgG deposits and complement activation on the surface of keratinocytes. Complement activation has been implicated in the pathogenesis with C3 deposits in about 90% of patients. Objective: In order to further elucidate the role of complement in PV and to define which cytokines play a role in C3 mRNA expression, we performed an in vitro study in human keratinocytes. Methods: Normal human epidermal keratinocytes (NHuK) were incubated with PV serum and C3 mRNA was measured. We previously had shown that IL-1α and TNF-α. are expressed in PV in vivo and in vitro. Since cytokines are able to modulate complement activation, mRNA expression was evaluated in a similar experiment after pretreatment using antibodies against IL-1α and TNF-α. Results: Incubation of NHuK with PV sera caused their detachment from the plates after 20-30 minutes with a complete acantholysis within 12 hours. An early C3 mRNA expression was seen after 30 minutes with a peak level after 1 hour. Blocking studies, using antibodies against human IL-1α and TNF-α in NHuK together with PV-IgG, showed reduction of in vitro induced acantholysis and inhibition of C3 mRNA expression. Conclusions: This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1α and TNF-α

Carbamazepine-induced hypersensitivity syndrome in a chile with epilepsy

Carbamazepine is an effective anticonvulsant and is considered the drug of first choice for the treatment of partial and secondarily generalized seizures. Although carbamazepine is well tolerated, many side effects have been reported in the literature. The majority of these adverse effects are transient and do not lead to the discontinuation of the therapy. We present a case of a female child, aged 11 years and 6 months, who showed an anticonvulsant hypersensitivity syndrome induced by carbamazepine. This syndrome is a rare, potentially life-threatening adverse drug reaction. The patient developed a cutaneous nonpruritic rash, associated with high fever, diffuse lymphadenopathy, and arthralgias on the knees and the ankles with local signs of arthritis. Laboratory examination showed a lymphocytosis, mild thrombocytopenia, marked eosinophilia, and high transaminases. Corticosteroid therapy (betametasone 0.5 mg x 3 day) was started and carbamazepine was gradually withdrawn changing to valproic acid, with complete control of the seizures. The fever and the rash reduced gradually, beginning from the face and then disappearing completely after 10 days. Laboratory results showed a clear improvement: after 7 days the patient showed a complete normalization of the above parameters, except for transaminases. The complete normalization of these enzymes was observed after 2 weeks from the disappearance of the skin rash

Rethinking the role of tumour necrosis factor-α in ultraviolet (UV) B-induced immunosuppression: Altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice

Background: Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha;. TNF-α produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-α have been demonstrated to inhibit UVB-induced immunosuppression in vivo. Objectives: To clarify further the role of TNF-α in UVB-induced immunosuppression and in cis-UCA immunosuppression. Methods: We performed a contact hypersensitivity (CHS) assay on gene-targeted mutant mice (TNFR1R2-/-) lacking genes for both receptors (p55 and p75) for TNF-α. Mice were either irradiated with UVB or injected intradermally with cis-UCA, sensitized with 2,4-dinitrofluoro-benzene, challenged on the ears and the response was measured. Results: The TNFR1R2-/- mice showed hyporesponsiveness in the CHS response compared with wild-type (P lt; 0.001), confirming the proinflammatory role of TNF-α. However, significant suppression of CHS was seen after irradiation and after cis-UCA injection in both locally (sensitization on irradiated site; P &lt; 0.05) and systemically (sensitization on non-irradiated site; P &lt; 0.05) sensitized wild-type and gene-targeted mice. Conclusions: These results demonstrate that TNF-α signalling is only partially involved in UVB-induced immunosuppression and does not play a major part in the cis-UCA immunosuppression mechanism

Urokinase plasminogen activator mRNA is induced by IL-1α and TNF-α in in vitro acantholysis

The role of urokinase type plasminogen activator (uPA) has been well documented in the pathogenesis of pemphigus vulgaris (PV). Activation of plasminogen into active serine protease plasmin initiates extracellular proteolysis leading to acantholysis but the mechanisms underlying this process are not clearly understood. We have previously shown that keratinocyte derived cytokines IL-1α and TNF-α are involved in PV-induced acantholysis. In the present study we sought to examine whether keratinocyte-derived IL-1α and TNF-α are correlated with uPA induction in keratinocytes during acantholysis. Normal human keratinocytes were incubated with diluted PV serum. mRNAs for IL-1α, TNF-α and uPA were examined with RT-PCR at various time points and acantholysis was measured. IL-1α, TNF-α and uPA mRNAs were all induced in keratinocytes following PV serum stimulation; IL-1α/TNF-α mRNAs' expression was earlier than the expression of uPA mRNA. To further examine the role of IL-1α, TNF-α and uPA in acantholysis, we performed antibody blocking studies. Anti-IL-la, anti-TNF-a and anti-uPA antibodies suppressed acantholysis by 76%, 80% and 90%, respectively. In addition, anti-IL-1α and anti-TNF-α antibodies inhibited uPA mRNA induction, whereas anti-uPA antibodies did not alter IL-1α/TNF-α mRNAs' expression. Our results confirm the role of uPA in acantholysis and suggest an involvement of IL-1α/TNF-α in uPA induction. © Blackwell Munksgaard, 2003

Carbamazepine-induced hypersensitivity syndrome in a chile with epilepsy

Carbamazepine is an effective anticonvulsant and is considered the drug of first choice for the treatment of partial and secondarily generalized seizures. Although carbamazepine is well tolerated, many side effects have been reported in the literature. The majority of these adverse effects are transient and do not lead to the discontinuation of the therapy. We present a case of a female child, aged 11 years and 6 months, who showed an anticonvulsant hypersensitivity syndrome induced by carbamazepine. This syndrome is a rare, potentially life-threatening adverse drug reaction. The patient developed a cutaneous nonpruritic rash, associated with high fever, diffuse lymphadenopathy, and arthralgias on the knees and the ankles with local signs of arthritis. Laboratory examination showed a lymphocytosis, mild thrombocytopenia, marked eosinophilia, and high transaminases. Corticosteroid therapy (betametasone 0.5 mg x 3 day) was started and carbamazepine was gradually withdrawn changing to valproic acid, with complete control of the seizures. The fever and the rash reduced gradually, beginning from the face and then disappearing completely after 10 days. Laboratory results showed a clear improvement: after 7 days the patient showed a complete normalization of the above parameters, except for transaminases. The complete normalization of these enzymes was observed after 2 weeks from the disappearance of the skin rash

Immune modulation in pemphigus vulgaris: Role of CD28 and IL-10

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice. Our results demonstrated that CD28-deficient mice (lacking a costimulatory signal for T cell activation) are 5-fold more sensitive to the development of PV than wild-type mice. To evaluate whether the higher incidence of disease was due to an impairment in intercellular adhesion of keratinocytes, we performed an in vitro acantholysis, using CD28(-/-) mice keratinocytes. No alteration in in vitro adhesion was detected in CD28(-/-)-type keratinocytes. Because the CD28 molecule plays a pivotal role in the induction of Th2 cytokines, we examined the levels of a prototypic Th2 cytokine (IL-10) in CD28(-/-) mice. Lower levels of IL-10 mRNA were found in lesions from CD28(-/-) mice. To determine whether pemphigus susceptibility in CD28(-/-) was related to IL-10 deficiency, we performed passive transfer experiments in IL-10(-/-) mice that demonstrated increased blisters compared with controls. To confirm that IL-10 is involved in the pathogenesis, rIL-10 was given with PV IgG. IL-10 significantly suppressed the disease activity. These data suggest a potential role of IL-10 in PV

Direct immunofluorescence diagnosis of pemphigus without biopsy

Background: Direct immunofluorescence (DIF) is a necessary examination tool for the diagnosis of pemphigus. The suction-blister-method splits the skin at the lamina lucida and it is possible with a scalpel to separate the entire epidermis from the dermis. Objective: The study was to determine whether DIF is reliable on epidermal sheets separated using a suction apparatus. Methods: Thirteen patients were selected for this study: (nine with pemphigus vulgaris (PV), one with paraneoplastic pemphigus (PP), and three with pemphigus erythematosus (PE). Frozen epidermal sheets, separated from the dermis with a scalpel, were used as a substrate. Diagnosis with routine fluorescein isothiocyanate (FITC) antibodies was made. Results: In all patients a pericellular deposition of IgG was evident and in eight of these patients a pericellular deposition of C3 was present. In two cases of PE and one of PP, the C3 deposits were also present in the lower part of basal keratinocytes. Conclusion: This diagnostic method without skin biopsy is easy to perform and, together with the histology and clinical aspects, could be a useful tool in the diagnosis of pemphigus. We recommend this method when the patient is allergic to local anaesthetics, the patient easily produces hypertrophic scars, or in follow-up of already biopsied patients