Assiut University Hospitals

Background: Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease. Purpose: To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease. Data Sources: MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions. Study Selection: Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs. Data Extraction: 2 reviewers independently extracted data and assessed the quality of reporting. Data Synthesis: 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events. Limitations: The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined. Conclusion: Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk-benefit ratios and patient preferences in this population. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Cell death was first described in rabbit ovaries (Graaffian follicles), the phenomenon being called 'chromatolysis' rather than apoptosis. In humans, the ovarian endowment of primordial follicles is established during fetal life. Apoptotic cell death depletes this endowment by at least two-thirds before birth, executed with the help of several players and pathways conserved from worms to humans. To date, apoptosis has been reported to be involved in oogenesis, folliculogenesis, oocyte loss/selection and atresia. Several pro-survival and pro-apoptotic molecules are involved in ovarian apoptosis with the delicate balance between them being the determinant for the final destiny of the follicular cells. This review critically analyses the current knowledge about the biological roles of these molecules and their relevance to the dynamics of follicle development. It also presents the existing literature and assesses the gaps in our knowledge.

Repetitive transcranial magnetic stimulation (rTMS) or sham stimulation was given over the motor cortex daily for 10 days to two randomly assigned groups of 26 patients with acute ischemic stroke. Patients otherwise continued their normal treatment. Disability scales measured before rTMS, at the end of the last rTMS session, and 10 days later showed that real rTMS improved patients' scores more than sham.

BACKGROUND: Three checkpoint inhibitor drugs have been approved by the US Food and Drug Administration for use in specific types of cancers. While the results are promising, severe immunotherapy-related adverse events (irAEs) have been reported. OBJECTIVES: To conduct a systematic review of case reports describing the occurrence of irAEs in patients with cancer following checkpoint blockade therapy, primarily to identify potentially unrecognized or unusual clinical findings and toxicity. DATA SOURCES: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane CENTRAL with no restriction through August 2015. STUDY SELECTION: Studies reporting cases of cancer develop irAEs following treatment with anti CTLA-4 (ipilimumab) or anti PD-1 (nivolumab or pembrolizumab) antibodies were included. DATA EXTRACTION: We extracted data on patient characteristics, irAEs characteristics, how irAEs were managed, and their outcomes. DATA SYNTHESIS: 191 publications met inclusion criteria, reporting on 251 cases. Most patients had metastatic melanoma (95.6%), and the majority were treated with ipilimumab (93.2%). Autoimmune colitis, hepatitis, endocrinopathies, and cutaneous irAEs were the most frequently reported irAEs in ipilimumab treated patients. A broad spectrum of toxicities were reported for almost every body system. Moreover, well-defined diseases such as sarcoidosis, polyarthritis, polymyalgia rheumatica/arteritis, lupus, celiac disease, dermatomyositis, and Vogt-Koyanagi-like syndrome were reported. The most frequent irAEs reported with anti-PD1 agents were dermatitis for pembrolizumab, and thyroid disease and pneumonitis for nivolumab. Complete resolution of adverse events occurred in most cases. However, persistent irAEs and death were reported, mainly in patients treated with ipilimumab. LIMITATIONS: Our study is limited by information available in the original reports. CONCLUSIONS: Evidence from case reports shows that cancer patients develop irAEs following checkpoint blockade therapy, and can occasionally develop clearly defined autoimmune systemic diseases. While discontinuation of therapy and/or treatment can result in resolution of irAEs, long-term sequelae and death have been reported.

Every living organism on the surface of the earth is exposed to the ultraviolet (UV) fraction of the sunlight. This electromagnetic energy has both life-giving and life-endangering effects. UV radiation can damage DNA and thus mutagenize several genes involved in the development of the skin cancer. The presence of typical signature of UV-induced mutations on these genes indicates that the ultraviolet-B part of sunlight is responsible for the evolution of cutaneous carcinogenesis. During this process, variable alterations of the oncogenic, tumor-suppressive, and cell-cycle control signaling pathways occur. These pathways include (a) mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor-suppressor gene in basal cell carcinomas, (b) an activated mitogenic ras pathway and mutated p53 in squamous cell carcinomas, and (c) an activated ras pathway, inactive p16, and p53 tumor suppressors in melanomas. This review presents background information about the skin optics, UV radiation, and molecular events involved in photocarcinogenesis.

BACKGROUND: Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication. METHODS: We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases. RESULTS: Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011). CONCLUSIONS: MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.

RATIONALE & OBJECTIVE: The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding including treatment in the adjuvant setting, the immune related toxicities associated with CPI can limit the efficacy of these agents. The literature on the nephrotoxicity of CPI is limited. Here, we present cases of biopsy proven acute tubulointerstitial nephritis (ATIN) and glomerulonephritis (GN) induced by CPIs and discuss potential mechanisms of these adverse effects. STUDY DESIGN, SETTING, & PARTICIPANTS: We retrospectively reviewed all cancer patients from 2008 to 2018 who were treated with a CPI and subsequently underwent a kidney biopsy at The University of Texas MD Anderson Cancer Center. RESULTS: We identified 16 cases diagnosed with advanced solid or hematologic malignancy; 12 patients were male, and the median age was 64 (range 38 to 77 years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14 weeks (range 6-56 weeks). The average time from AKI diagnosis to obtaining renal biopsy was 16 days (range from 1 to 46 days). Fifteen cases occurred post anti-PD-1based therapy. ATIN was the most common pathologic finding on biopsy (14 of 16) and presented in almost all cases as either the major microscopic finding or as a mild form of interstitial inflammation in association with other glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 cases. Steroids and further immunosuppression were used in most cases as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving complete to partial renal recovery. CONCLUSIONS: Our data demonstrate that CPI related AKI occurs relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most common pathological finding; however it can frequently co-occur with other glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI.

BACKGROUND: Checkpoint inhibitors (CPIs) have revolutionized the treatment of cancer, but their use remains limited by off-target inflammatory and immune-related adverse events. Solid organ transplantation (SOT) recipients have been excluded from clinical trials owing to concerns about alloimmunity, organ rejection, and immunosuppressive therapy. Thus, we conducted a retrospective study and literature review to evaluate the safety of CPIs in patients with cancer and prior SOT. METHODS: Data were collected from the medical records of patients with cancer and prior SOT who received CPIs at The University of Texas MD Anderson Cancer Center from January 1, 2004, through March 31, 2018. Additionally, we systematically reviewed five databases through April 2018 to identify studies reporting CPIs to treat cancer in SOT recipients. We evaluated the safety of CPIs in terms of alloimmunity, immune-related adverse events, and mortality. We also evaluated tumor response to CPIs. RESULTS: Thirty-nine patients with allograft transplantation were identified. The median age was 63 years (range 14-79 years), 74% were male, 62% had metastatic melanoma, 77% received anti-PD-1 agents, and 59% had prior renal transplantation, 28% hepatic transplantation, and 13% cardiac transplantation. Median time to CPI initiation after SOT was 9 years (range 0.92-32 years). Allograft rejection occurred in 41% of patients (11/23 renal, 4/11 hepatic, and 1/5 cardiac transplantations), at similar rates for anti-CTLA-4 and anti-PD-1 therapy. The median time to rejection was 21 days (95% confidence interval 19.3-22.8 days). There were no associations between time since SOT and frequency, timing, or type of rejection. Overall, 31% of patients permanently discontinued CPIs because of allograft rejection. Graft loss occurred in 81%, and death was reported in 46%. Of the 12 patients with transplantation biopsies, nine (75%) had acute rejection, and five of these rejections were T cell-mediated. In melanoma patients, 36% responded to CPIs. CONCLUSIONS: SOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients.

OBJECTIVE: To assess the benefit of the recombinant human interleukin-1 receptor antagonist anakinra in treating pediatric patients with secondary hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) associated with rheumatic and nonrheumatic conditions. METHODS: A retrospective chart review of all anakinra-treated patients with secondary HLH/MAS was performed at Children's of Alabama from January 2008 through December 2016. Demographic, clinical, laboratory, and genetic characteristics, outcomes data, and information on concurrent treatments were collected from the records and analyzed using appropriate univariate statistical approaches to assess changes following treatment and associations between patient variables and outcomes. RESULTS: Forty-four patients with secondary HLH/MAS being treated with anakinra were identified in the electronic medical records. The median duration of hospitalization was 15 days. The mean pretreatment serum ferritin level was 33,316 ng/ml and dropped to 14,435 ng/ml (57% decrease) within 15 days of the start of anakinra treatment. The overall mortality rate in the cohort was 27%. Earlier initiation of anakinra (within 5 days of hospitalization) was associated with reduced mortality (P = 0.046), whereas thrombocytopenia (platelet count <100,000/μl) and STXBP2 mutations were both associated with increased mortality (P = 0.008 and P = 0.012, respectively). In considering patients according to their underlying diagnosis, those with systemic juvenile idiopathic arthritis (JIA) had the lowest mortality rate, with no deaths among the 13 systemic JIA patients included in the study (P = 0.006). In contrast, those with an underlying hematologic malignancy had the highest mortality rate, at 100% (n = 3). CONCLUSION: These findings suggest that anakinra appears to be effective in treating pediatric patients with non-malignancy-associated secondary HLH/MAS, especially when it is given early in the disease course and when administered to patients who have an underlying rheumatic disease.

OBJECTIVE: To refine the previously developed scleroderma (systemic sclerosis [SSc]) gastrointestinal tract (GIT) instrument (SSC-GIT 1.0). METHODS: We administered the SSC-GIT 1.0 and the Short Form 36 to 152 patients with SSc; 1 item was added to the SSC-GIT 1.0 to assess rectal incontinence. In addition, subjects completed a rating of the severity of their GIT involvement (from very mild to very severe). Evaluation of psychometric properties included internal consistency reliability, test-retest reliability (mean time interval 1.1 weeks), and multitrait scaling analysis. RESULTS: Study participants were mostly women (84%) and white (81%); 55% had diffuse SSc. Self-rated severity of GIT involvement ranged from no symptoms to very mild (39%), mild (21%), moderate (31%), and severe/very severe (9%). Of an initial 53 items in the SSC-GIT 1.0, 19 items were excluded, leaving a 34-item revised instrument (the University of California, Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 [UCLA SCTC GIT 2.0]). Analyses supported 7 multi-item scales: reflux, distention/bloating, diarrhea, fecal soilage, constipation, emotional well-being, and social functioning. Test-retest reliability estimates were >/=0.68 and coefficient alphas were >/=0.67. Participants who rated their GIT disease as mild had lower scores on a 0-3 scale on all 7 scales. Symptom scales were also able to discriminate subjects with corresponding clinical GIT diagnoses. The Total GIT Score, developed by averaging 6 of 7 scales (excluding constipation), was reliable and provided greater discrimination between mild, moderate, and severe self-rated GIT involvement than individual scales. CONCLUSION: This study provides support for the reliability and validity of the UCLA SCTC GIT 2.0, an improvement over the SSC-GIT 1.0, and supports a Total GIT Score in SSc patients with GIT.

The development of hemostatic technologies that suit a diverse range of emergency scenarios is a critical initiative, and there is an increasing interest in the development of absorbable dressings that can be left in the injury site and degrade to reduce the duration of interventional procedures. In the current study, β-cyclodextrin polyester (CDPE) hydrogels serve as sacrificial macroporous carriers, capable of degradation under physiological conditions. The CDPE template enables the assembly of imprinted chitosan honeycomb-like monolithic mats, containing highly entangled nanofibers with diameters of 9.2 ± 3.7 nm, thereby achieving an increase in the surface area of chitosan to improve hemostatic efficiency. In vivo, chitosan-loaded cyclodextrin (CDPE-Cs) hydrogels yield significantly lower amounts of blood loss and shorter times to hemostasis compared with commercially available absorbable hemostatic dressings, and are highly biocompatible. The designed hydrogels demonstrate promising hemostatic efficiency, as a physiologically-benign approach to mitigating blood loss in tissue-injury scenarios.

BACKGROUND: Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX. METHODS: Data were collected from the medical records of patients diagnosed with irEC. The primary endpoint was time to symptom resolution for irEC for cases managed with IFX plus CS (IFX group) versus CS alone (CS group). Duration of CS, overall survival (OS), and time to treatment failure (TTF) were secondary endpoints. RESULTS: Among 75 patients with irEC, 52% received CS alone, and 48% received IFX. Despite higher grade colitis in the IFX group (grade 3/4: 86% vs. 34%; p < 0.001), median times to diarrhea resolution (3 vs. 9 days; p < 0.001) and to steroid titration (4 vs. 13 days; p < 0.001) were shorter in the IFX group than in the CS group without a negative impact on TTF or OS. Total steroid duration (median 35 vs. 51 days; p = 0.150) was numerically lower in the IFX group. CONCLUSIONS: Despite higher incidence of grade 3/4 colitis, IFX added to CS for the treatment of patients with irEC was associated with a significantly shorter time to symptom resolution. The data suggest that early introduction of IFX should be considered for patients with irEC until definitive prospective clinical trials are conducted.

BACKGROUND: The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation (tDCS) in the neurorehabilitation of Alzheimer's disease (AD). METHODS: Thirty-four AD patients were randomly assigned to three groups: anodal, cathodal, and sham tDCS. Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA, daily for 10 days. Each patient was submitted to the following psychometric assessments: mini-mental state examination (MMSE) and Wechsler adult intelligence scale-third edition at base line, at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions. Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session. RESULTS: Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS. Post hoc comparisons showed that both anodal and cathodal tDCS (ctDCS) improved MMSE in contrast to sham tDCS. Whereas, this was only true for ctDCS in the performance IQ. Remarkably, tDCS also reduced the P300 latency, but had no effect on motor cortex excitability. CONCLUSION: Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency, which is known to be pathologically increased in AD.

Splendore-Hoeppli phenomenon (asteroid bodies) is the in vivo formation of intensely eosinophilic material (radiate, star-like, asteroid or club-shaped configurations) around microorganisms (fungi, bacteria and parasites) or biologically inert substances. This study presents a literature review concerning Splendore-Hoeppli reaction in the mucocutaneous diseases. It examines the histopathological features, nature and differential diagnosis of this reaction. It also discusses the mucocutaneous infections and the non-infective diseases associated with it. Available studies indicate that several mucocutaneous infections can generate Splendore-Hoeppli reaction. The fungal infections include sporotrichosis, pityrosporum folliculitis, zygomycosis, candidiasis, aspergillosis and blastomycosis. The bacterial infections include botryomycosis, nocardiosis and actinomycosis. The parasitic conditions include orbital pythiosis, strongyloidiasis, schistosomiasis and cutaneous larva migrans. In addition, Splendore-Hoeppli reaction may be seen with non-infective pathology such as hypereosinophilic syndrome and allergic conjunctival granulomas. The Splendore-Hoeppli reaction material comprises antigen-antibody complex, tissue debris and fibrin. Although the exact nature of this reaction is unknown, it is thought to be a localized immunological response to an antigen-antibody precipitate related to fungi, parasites, bacteria or inert materials. The characteristic formation of the peribacterial or perifungal Splendore-Hoeppli reaction probably prevents phagocytosis and intracellular killing of the insulting agent leading to chronicity of infection. To conclude, Splendore-Hoeppli reaction is a tell tale of a spectrum of infections and reactive conditions. The molecular pathways involved in the development of this reaction are open for future investigations.

BACKGROUND: Gastric bypass and duodenal switch are currently performed bariatric surgical procedures. Uncontrolled studies suggest that duodenal switch induces greater weight loss than gastric bypass. OBJECTIVE: To determine whether duodenal switch leads to greater weight loss and more favorable improvements in cardiovascular risk factors and quality of life than gastric bypass. DESIGN: Randomized, parallel-group trial. (ClinicalTrials.gov registration number: NCT00327912) SETTING: 2 academic medical centers (1 in Norway and 1 in Sweden). PATIENTS: 60 participants with a body mass index (BMI) between 50 and 60 kg/m(2). INTERVENTION: Gastric bypass (n = 31) or duodenal switch (n = 29). MEASUREMENTS: The primary outcome was the change in BMI after 2 years. Secondary outcomes included anthropometric measures; concentrations of blood lipids, glucose, insulin, C-reactive protein, and vitamins; and health-related quality of life and adverse events. RESULTS: Fifty-eight of 60 participants (97%) completed the study. The mean reductions in BMI were 17.3 kg/m(2) (95% CI, 15.7 to 19.0 kg/m(2)) after gastric bypass and 24.8 kg/m(2) (CI, 23.0 to 26.5 kg/m(2)) after duodenal switch (mean between-group difference, 7.44 kg/m(2) [CI, 5.24 to 9.64 kg/m(2)]; P < 0.001). Total cholesterol concentration decreased by 0.24 mmol/L (CI, -0.03 to 0.50 mmol/L) (9.27 mg/dL [CI, -1.16 to 19.3 mg/dL]) after gastric bypass and 1.07 mmol/L (CI, 0.79 to 1.35 mmol/L) (41.3 mg/dL [CI, 30.5 to 52.1 mg/dL]) after duodenal switch (mean between-group difference, 0.83 mmol/L [CI, 0.48 to 1.18 mmol/L]; 32.0 mg/dL [CI, 18.5 to 45.6 mg/dL]; P ≤ 0.001). Reductions in low-density lipoprotein cholesterol concentration, anthropometric measures, fat mass, and fat-free mass were also greater after duodenal switch (P ≤ 0.010 for each between-group comparison). Both groups had reductions in blood pressure and mean concentrations of glucose, insulin, and C-reactive protein, with no between-group differences. The duodenal switch group, but not the gastric bypass group, had reductions in concentrations of vitamin A and 25-hydroxyvitamin D. Most Short Form-36 Health Survey dimensional scores improved in both groups, with greater improvement in 1 of 8 domains (bodily pain) after gastric bypass. From surgery until 2 years, 10 participants (32%) had adverse events after gastric bypass and 18 (62%) after duodenal switch (P = 0.021). Adverse events related to malnutrition occurred only after duodenal switch. LIMITATION: Clinical experience was greater with gastric bypass than with duodenal switch at the study centers. CONCLUSION: Duodenal switch surgery was associated with greater weight loss, greater reductions of total and low-density lipoprotein cholesterol concentrations, and more adverse events. Improvements in other cardiovascular risk factors and quality of life were similar after both procedures. PRIMARY FUNDING SOURCE: South-Eastern Norway Regional Health Authority.

Between 1993 and 1998, 32 male patients with brachial plexus injuries were surgically treated. Eighteen interfascicular grafting and 71 extraplexal neurotization procedures were performed separately or in combination. Donor nerves were the intercostals, spinal accessory, phrenic, contralateral C7, and cervical plexus, in order of frequency. Patients were followed for a minimum of 24 (average, 35) months. Biceps function was best following grafting the musculocutaneous nerve itself, or neurotization with the phrenic nerve (100 percent grade 4), followed by neurotization with the intercostals (89.5 percent grade 3 or more) and last, grafting the C5 root or upper trunk (grade 3 in one of three patients). Phrenic to suprascapular neurotization produced the best results of shoulder abduction (40 to 90 degrees), followed by combined neurotization of the spinal accessory to suprascapular and phrenic to axillary (20 to 90 degrees). Sensory recovery over the lateral forearm and palm varied from S2 to S3+, according to the method of reconstruction.

Objective The objective of this paper is to conduct a systematic review and meta-analysis on the risk of developing elevated antiphospholipid (aPL) antibodies and related thromboembolic and/or pregnancy events following a viral infection. Method We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane Central Register of Controlled Trials through June 2016. Independent observational studies of elevated aPL antibodies in patients with a viral infection compared with controls or patients with lupus were included. Results We analyzed 73 publications for 60 studies. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were most commonly reported. Compared with healthy controls, patients with HIV were more likely to develop elevated anticardiolipin (aCL) antibodies (risk ratio (RR) 10.5, 95% confidence interval (CI) 5.6-19.4), as were those with HCV (RR 6.3, 95% CI 3.9-10.1), hepatitis B virus (HBV) (RR 4.2, 95% CI 1.8-9.5), and Epstein-Barr virus (EBV) (RR 10.9 95% CI 5.4-22.2). The only statistically significant increased risk for anti-β2-glycoprotein I (anti-β2-GPI) antibodies was observed in patients with HCV (RR 4.8 95% CI 1.0-22.3). Compared with patients with lupus, patients with HIV were more likely to develop elevated aCL antibodies (RR 1.8, 95% CI 1.3-2.6), and those with EBV, elevated anti-β2-GPI antibodies (RR 2.2, 95% CI 1.3-3.9). Thromboembolic events were most prevalent in patients with elevated aPL antibodies who had HCV (9.1%, 95% CI 3.0-18.1), and HBV (5.9%, 95% CI 2.0-11.9) infections, and pregnancy events were most prevalent in those with parvovirus B19 (16.3%, 95% CI 0.78-45.7). However, compared to virus-infected patients with negative aPL antibodies, the only statistically significant increased risk was observed in those with HCV and positive aPL. Conclusions Viral infection can increase the risk of developing elevated aPL antibodies and associated thromboembolic events. Results are contingent on the reported information.

OBJECTIVE: The objective of this study was to conduct a systematic review of case reports documenting the development of antiphospholipid syndrome or antiphospholipid syndrome-related features after an infection. METHODS: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and The Cochrane Library - CENTRAL through March 2015 without restrictions. Studies reporting cases of antiphospholipid syndrome or antiphospholipid syndrome-related features following an infection were included. RESULTS: Two hundred and fifty-nine publications met inclusion criteria, reporting on 293 cases. Three different groups of patients were identified; group 1 included patients who fulfilled the criteria for definitive antiphospholipid syndrome (24.6%), group 2 included patients who developed transient antiphospholipid antibodies with thromboembolic phenomena (43.7%), and group 3 included patients who developed transient antiphospholipid antibodies without thromboembolic events (31.7%). The most common preceding infection was viral (55.6%). In cases that developed thromboembolic events Human immunodeficiency and Hepatitis C viruses were the most frequently reported. Parvovirus B19 was the most common in cases that developed antibodies without thromboembolic events. Hematological manifestations and peripheral thrombosis were the most common clinical manifestations. Positive anticardiolipin antibodies were the most frequent antibodies reported, primarily coexisting IgG and IgM isotypes. Few patients in groups 1 and 2 had persistent antiphospholipid antibodies for more than 6 months. Outcome was variable with some cases reporting persistent antiphospholipid syndrome features and others achieving complete resolution of clinical events. CONCLUSIONS: Development of antiphospholipid antibodies with all traditional manifestations of antiphospholipid syndrome were observed after variety of infections, most frequently after chronic viral infections with Human immunodeficiency and Hepatitis C. The causal relationship between infection and antiphospholipid syndrome cannot be established, but the possible contribution of various infections in the pathogenesis of antiphospholipid syndrome need further longitudinal and controlled studies to establish the incidence, and better quantify the risk and the outcomes of antiphospholipid-related events after infection.

BACKGROUND: The ideal intraocular lens in cases of aphakia without capsular support is debated. Choices include anterior chamber lenses, iris- or scleral-sutured lenses, and iris-claw lenses. Our aim was to report our long-term evaluation of the use of retropupillary implantation of the Artisan iris-claw intraocular lens (RPICIOL) in several aphakic conditions without capsular support. METHODS: A retrospective analysis of consecutive 320 eyes of 320 patients (222 males and 98 females) without capsular support in which we performed RPICIOL implantation in post-traumatic aphakia (141 eyes, group 1), post-cataract surgery aphakia (122 eyes, group 2), and in cases in which penetrating keratoplasty was associated with vitrectomy (57 eyes, group 3). Either anterior or posterior vitrectomy procedures were performed with 20-, 23-, or 25-gauge techniques for different associated anterior or posterior segment indications. We reviewed the refractive outcome, anatomical outcome, long-term stability of the implants, and possible long-term complications. RESULTS: The mean patient age was 59.7 years (range, 16-84 years) in group 1; 60.1 years (range, 14-76 years) in group 2; and 65.8 years (range, 25-71.5 years) in group 3. The mean follow-up time was 5.3 years (range, 1 month to 8 years). At the end of the follow-up period, the mean post-operative best-corrected LogMAR visual acuity was 0.6 (range, perception of light to 0.3) in group 1; 0.3 (range, 0.5-0.1) in group 2; and 0.6 (range, hand movement to 0.2) in group 3. Disenclavation of RPICIOLs occurred in three cases because of slippage of one of the iris-claw haptics and spontaneous complete posterior dislocation occurred in one case. One case presented with retinal detachment, and no cases of uveitis were observed. Eight cases complained of chronic dull pain, and severe iridodonesis was seen in five cases. One case of post-operative macular edema was observed without post-operative increase in the mean intraocular pressure. There was no statistically different change in the endothelial cell density (cells/mm(2)) at the end of the follow-up period. CONCLUSIONS: RPICIOL for secondary implantations is a valid alternative strategy to scleral-fixated or angle-supported IOL implantation.

OBJECTIVE: To evaluate the effect on perinatal and postnatal survival of vesicoamniotic shunt (VAS) as treatment for fetal lower urinary tract obstruction (LUTO). METHODS: An electronic search of Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus using relevant search terms was conducted from inception to June 2015 to identify studies comparing outcomes of VAS vs conservative management for treatment of LUTO. Cohort studies and clinical trials were considered eligible. Single-arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for exclusion. Two reviewers extracted independently data in a standardized form, including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratio (OR) and 95% CI. RESULTS: Of the 423 abstracts retrieved, nine studies were eligible for inclusion. These studies included 112 fetuses treated with VAS and 134 that were managed conservatively. There was heterogeneity in study design. Although the data demonstrated a difference in effect estimates between the study arms in terms of perinatal survival (OR, 2.54 (95% CI, 1.14-5.67)), there was no difference in 6-12-month survival (OR, 1.77 (95% CI, 0.25-12.71)) or 2-year survival (OR, 1.81 (95% CI, 0.09-38.03)). In addition, there was no difference in effect on postnatal renal function between fetuses that underwent intervention and those that did not (OR, 2.09 (95% CI, 0.74-5.94)). CONCLUSIONS: Available data seem to support an advantage for perinatal survival in fetuses treated with VAS compared with conservative management. However, 1-2-year survival and outcome of renal function after VAS procedure remain uncertain. Further studies are necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies according to GRADE guidelines. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.