Helicobacter pylori Infection of the Gastric Mucosa and Ocular Adnexa-Lack of Association With Ocular Adnexal Lymphoma.

PURPOSE: Helicobacter pylori could theoretically induce ocular adnexal lymphoma (OAL) via 2 mechanisms: the first is that of infection within the ocular adnexa and the second is that of infection within the gastric mucosa, leading to the malignant transformation of lymphocytes that migrate to the ocular adnexa, forming a primary "ectopic" cancer. This study investigated if an association exists between gastric H. pylori or ocular adnexal H. pylori and OAL. METHODS: Prospective case-control study including cases with OAL and controls with nonlymphomatous pathologies. Gastric H. pylori infection was assessed via serologic antibody testing. Ocular adnexal infection was assessed via polymerase chain reaction testing for H. pylori and Chlamydia psittaci within ocular adnexal samples. RESULTS: Seventy-two patients were enrolled, of whom 18 had lymphoma and 54 nonlymphomatous pathologies. H. pylori antibodies were present in 5 cases (28%) and 18 controls (33%) (95% CI, 0.24%-2.50%, p = 0.78). All ocular adnexal specimens were negative for H. pylori and C. psittaci infection. The only relevant statistically significant difference between cases and controls was a history of gastric ulcer (95% CI, 1.23%-44.80%, p = 0.03). CONCLUSIONS: In the study's population, infection of gastric mucosa with H. pylori does not appear to influence the development of OAL. Also, H. pylori or C. psittaci infection within the ocular adnexa does not appear to influence the development of OAL. In the study's practice, authors do not recommend antibiotic administration or routine gastroscopy for patients with OAL. The authors do recommend referral of OAL patients with gastric symptoms to a gastroenterologist.

Guidelines for vismodegib in the management of periocular basal cell carcinoma.

OBJECTIVE: The management of advanced basal cell carcinoma (BCC) in the periocular region remains a clinical challenge. Vismodegib (ErivedgeTM) has been approved in 2013 by Health Canada for adult patients with "histologically confirmed metastatic BCC or locally advanced BCC inappropriate for surgery or radiation." An expert consensus was sought to create a standardised approach in the use of this novel treatment. METHODS: Fourteen practicing oculoplastic surgeons across Canada were involved in formulating and reviewing guidelines until consensus was reached. A consultancy meeting was followed by further ratification of guidelines over email. Two voting surveys were performed of the group to objectively assess agreement over each statement within the guidelines. Ratification continued until at least two-thirds of the group agreed on every guideline statement. RESULTS: The guidelines summarize 21 statements in a major and minor criteria format. A multidisciplinary team review is suggested for each patient with the involvement of recommended specialists. The internal survey revealed 100% agreement over 9 statements, 91.7% agreement over 8 statements, 83.3% agreement over 4 statements, and 2 statements had 66.7% and 58.7% agreement each. All statements with less than 91.7% agreement were surveyed again, and they were kept, modified, or removed on the basis of a consensus of over 66.7%. CONCLUSIONS: These guidelines serve to act as a framework for physicians considering vismodegib for the medical management of patients with advanced or metastatic periocular BCC. Future applications, including neoadjuvant uses of the drug, may become apparent through further research.

Delayed linkage to HIV care among asylum seekers in Quebec, Canada.

BACKGROUND: Migrants represent an increasing proportion of people living with HIV in many developed countries. We aimed to describe the HIV care cascade and baseline genotypic resistance for newly diagnosed asylum seekers referred to the McGill University Health Centre (MUHC) in Montreal, Quebec, Canada. METHODS: We conducted a retrospective cohort study of patients linked to the MUHC from June 1, 2017 to October 31, 2018. We calculated the median time (days; interquartile range (IQR)) from: 1) entry into Canada to immigration medical examination (IME) (i.e. HIV screening); 2) IME to patient notification of diagnosis; 3) notification to linkage to HIV care (defined as a CD4 or viral load (VL) measure); 4) linkage to HIV care to combination antiretroviral therapy (cART) prescription; and 5) cART prescription to viral suppression (defined as a VL < 20 copies/mL). We reviewed baseline genotypes and interpreted mutations using the Stanford University HIV Drug Resistance Database. We calculated the proportion with full resistance to > 1 antiretroviral. RESULTS: Overall, 43% (60/139) of asylum seekers were newly diagnosed in Canada. Among these, 62% were late presenters (CD4 < 350 cells/µl), 22% presented with advanced HIV (CD4 < 200 cells/µl), and 25% with high-level viremia (VL > 100,000 copies/ml). Median time from entry to IME: 27 days [IQR:13;55]; IME to notification: 28 days [IQR:21;49]; notification to linkage: 6 days [IQR:2;19]; linkage to cART prescription: 11 days [IQR:6;17]; and cART to viral suppression: 42 days [IQR:31;88]; 45% were linked to HIV care within 30 days. One-fifth (21%) had baseline resistance to at least one antiretroviral agent; the K103 N/S mutation was the most common mutation. CONCLUSIONS: While the majority of newly diagnosed asylum seekers were late presenters, only 45% were linked to care within 30 days. Once linked, care and viral suppression were rapid. Delays in screening and linkage to care present increased risk for onward transmission, and in the context of 21% baseline resistance, consideration of point-of-care testing and immediate referral at IME screening should be made.

Prospective case-control trial evaluating silicone gel for the treatment of direct brow lift scars.

OBJECTIVE: To evaluate the effectiveness of a topical silicone gel on scars in patients who had undergone bilateral direct brow lift surgery. DESIGN: A randomized double-blind clinical trial with a placebo applied to one scar and topical silicone gel (Dermatix Ultra; Valeant Pharmaceuticals, Laval, Que.) used on the other scar for 2 months. PARTICIPANTS: Twelve patients (for a total of 24 surgical scars evaluated) were included in the study. METHODS: This study was performed in 2 academic hospitals of the University of Montreal in Montreal, Que. (Maisonneuve-Rosemont Hospital and Notre-Dame Hospital). Inclusion criteria were all bilateral direct brow lift surgeries performed in our hospitals. Exclusion criteria included revision surgery, silicone or latex allergy, and wound infection. Each patient received 2 tubes (1 with silicone gel and 1 with placebo) and applied 1 tube to their right brow scar and the other tube to their left brow scar, following the preassigned instructions. The patient and surgeon were blinded to the nature of the substance that was applied to each scar. At each visit, pictures of both scars were taken, and a questionnaire titled "The Patient and Observer Scar Assessment Scale" was filled out by the patient and the surgeon. A grade ranging from 0 to 10 was given on the multiple criteria in the questionnaire, and the sum of these grades was subsequently used for the data analysis. A lower sum was interpreted as improved scarring. At the end of the study, an independent evaluator graded both scars based on pictures. Follow-up visits were held on day 7, week 6, month 3, and month 6 after surgery. A comparison of the experimental and placebo group was performed with nonparametric tests of Wilcoxon signed rank. RESULTS: A total of 24 scars of 12 patients were analyzed (based on 4 follow-up visits). General improvement of scars was reported by the patient, the surgeon, and based on pictures. No statistically significant difference was found between the group treated with silicone gel and the group treated with placebo. All tests had a p value ≥0.08. CONCLUSIONS: We did not find a statistically significant difference between scars treated with silicone gel and scars treated with the placebo after direct brow lift surgery.

Chemotherapy-related cognitive impairment or « chemobrain ¼: concept and state of art.

Cognitive complaints are frequent in patients who received chemotherapy for a non-CNS cancer. These observations have been described as « chemobrain ¼. However, studies results are contradictory concerning the implication of chemotherapy in the onset of cognitive defects. Moreover, other factors as mood, anxiety and fatigue are often associated in this population and could be confounding. This article present principal results of research in human experiencing chemobrain, concerning clinical presentation, neuropsychological examination, imaging techniques and treatment possibilities. Physiopathological hypothesis are presented. The implication of hormonotherapy is also discussed.

Comparison of Two Polypropylene Frontalis Suspension Techniques in 92 Patients With Oculopharyngeal Muscular Dystrophy.

PURPOSE: To compare the functional outcome of the polypropylene trapezoid frontalis suspension with the polypropylene modified Crawford frontalis suspension in a large cohort of patients with oculopharyngeal muscular dystrophy. METHODS: Retrospective, nonrandomized comparative case series. Patients with oculopharyngeal muscular dystrophy who underwent bilateral polypropylene frontalis suspension were selected for chart review. Main outcome measures were margin reflex distance, duration of surgery, and ptosis recurrence. RESULTS: Ninety-two patients qualified for chart review; 39 patients underwent the trapezoid sling and 53 patients the modified Crawford sling. There was no difference in preoperative margin reflex distance or levator function between the 2 surgical groups. Postoperative improvement in margin reflex distance was 2.95 ± 1.56 mm in the trapezoid group compared with 2.85 ± 1.65 mm in the modified Crawford group (p = 0.67). Duration of surgery was 40.49 ± 13.33 minutes in the trapezoid group compared with 53.77 ± 16.04 minutes in the modified Crawford group (p < 0.001). Five percent of eyes in the trapezoid group had ptosis recurrence compared with 13% of eyes in the modified Crawford group (p = 0.07). CONCLUSION: Both polypropylene frontalis suspension techniques generated an equivalent increase in margin reflex distance. However, the trapezoid frontalis suspension required less operative time and trended toward a lower rate of ptosis recurrence.

Prospective Evaluation of the Impact of Antiangiogenic Treatment on Cognitive Functions in Metastatic Renal Cancer.

BACKGROUND: Little is known about the cognitive effects of antiangiogenic therapies (AATs) in metastatic renal cell carcinoma (mRCC) and their relation with fatigue. OBJECTIVE: To evaluate the impact of AATs on cognition and its connection with fatigue and quality of life (QoL) in patients with mRCC. DESIGN, SETTING, AND PARTICIPANTS: This prospective study enrolled 75 patients starting AAT as first or second line for mRCC and assessed them at 3 mo (n=58) and 6 mo (n=50). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed objective cognitive decline with a neuropsychological battery of tests and cognitive complaint, fatigue, and QoL with validated self-reported questionnaires using the Fisher exact test, Wilcoxon test, and Spearman correlation coefficient. RESULTS AND LIMITATIONS: A decline of cognitive functions was observed in 18 patients (31%) including 13 without cognitive impairment at baseline. The score of fatigue was increased in all patients except one. A relationship between cognitive complaints and fatigue was observed (p<0.05) but not with objective cognitive decline. Cognitive complaints and fatigue had a significant impact on most of the domains of QoL (p<0.01). A positive correlation was found between fatigue and inflammatory markers but not with cognition. The main limitation of this study is the absence of a control group. CONCLUSIONS: AAT induced cognitive decline in patients with mRCC independently of fatigue. These side effects affecting QoL should be better assessed in clinical trials and taken into account in routine practice. PATIENT SUMMARY: Fatigue is a well-known effect of antiangiogenic therapies (AATs) of cancer. The study performed in patients with treated metastatic renal cancer shows a decline of cognitive functions induced by AATs, such as information-processing speed or working memory, in a third of patients, independently of fatigue. Patients on AATs should be informed of these possible adverse effects.

Neck and spine injuries in Canadian cheerleaders: An increasing trend.

BACKGROUND/PURPOSE: Cheerleading, now increasingly practiced in Canada, has a high propensity to cause traumatic neck and spine injuries. We aimed to evaluate the importance of neck and spine injuries in the practice of cheerleading and their occurrence mechanisms in order to propose preventive measures. METHODS: A retrospective cohort study of cheerleading injuries extracted from the Canadian Hospitals Injury Reporting and Prevention Program database between 1990 and 2010 was performed. RESULTS: Overall, there were 1496 cases of injuries documented secondary to cheerleading (median age 15, 4 (IQR=2, 2) years; 1410 women (94%)). Of those, 125 cases (8%) were neck and spine injuries. The most frequent injury was a sprain/strain (47%). More severe injuries included fractures (4%), muscle or tendon injury (3%), dislocation (1%), and nerve injury (1%). Over half of these injuries were caused by either falling from (26%) or basing/spotting a stunt from height (26%). Other mechanisms include being thrown/falling from a high toss (10%) and falling from a pyramid (8%). Of the 125 cases, 3 (2, 4%) were admitted to hospital. CONCLUSIONS: Most neck and spine injuries were related to stunts. Although the proportion of serious injury is low, the increasing trend for the practice of cheerleading calls for preventive measures.

Muscle prolapse after harvesting autogenous fascia lata used for frontalis suspension in children.

PURPOSE: To evaluate the long-term results at the donor site in children who underwent harvesting of autogenous fascia lata for frontalis suspension in ptosis correction. METHODS: The study design consists of a retrospective, nonrandomized case series. Medical records of 30 patients were reviewed. Each patient was reexamined, evaluating bulging at the donor site. Muscle prolapse was graded as not visible and not palpable, not visible but palpable, mildly visible, or obviously visible. Measurement of the width and length of the leg scar was recorded. Discomfort at the donor site was graded as no discomfort, occasional discomfort, or frequent discomfort. RESULTS: The mean age of the patients was 7 years (range, 1-15), with a mean follow-up period of 27 months (range, 3-63 months). Fifteen patients (50%) had invisible and impalpable bulging, 2 patients (6.7%) had invisible but palpable bulging, 5 patients (16.7%) had mildly visible bulging, and 8 patients (26.7%) had obviously visible bulging. The mean width of the scar was 7.5 mm, and the mean length was 3.6 cm. Twenty-seven patients (90%) had no functional discomfort of the leg, 2 patients (6.7%) had occasional discomfort, and 1 patient (3.3%) had frequent discomfort that occurred during exercise. CONCLUSIONS: After fascia lata harvesting, most patients had no cosmetic complaints or functional complications. The technique of harvesting fascia lata using a Crawford stripper seems to be safe and satisfactory.

Comparison of anesthetic and surgical outcomes of dacryocystorhinostomy using loco-regional versus general anesthesia.

OBJECTIVE: The aim of this study was to compare anesthetic and surgical outcomes of external dacryocystorhinostomy (DCR) under loco-regional anesthesia (LA) versus general anesthesia (GA). METHODS: Retrospective chart review of all patients that underwent DCR by one surgeon (IH) over the course of a ten-year period (April 1994 to March 2003). RESULTS: A total of 221 DCR were performed on 209 patients during the study period: 71 were done under LA (72.0 ± 13.3 years) and 150 under GA (64.2 ± 13.0 years; P<0.001). LA patients had a shorter length of surgery (56.2 ± 15.3 vs. 64.0 ± 18.1 minutes; P=0.001) and required less antiemetic drugs during the first four hours after surgery (P=0.03). Pain was well controlled and patients were comfortable per- and post-operatively. Excluding ecchymosis (38.0% LA vs. 21.6% GA; P=0.01), the rate of minor complications did not differ between the two groups: infection, inflammation or edema (14.1 vs. 18.2%; P=0.13), hematoma (1.4 vs. 2.7%; P=0.52) and epistaxis (22.5 vs. 14.2%; P=0.44). Rates of recurrent symptoms and/or re-intervention (11.3 vs. 13.1%; P=0.91) were comparable for LA and GA. CONCLUSION: This study suggests that external DCR performed under LA and monitored anesthesia care may be advantageous. The length of surgery is reduced, post-operative side effects are diminished, and excluding ecchymosis, the rate of minor complications is not increased. These benefits are desirable in a predominantly elderly population where avoidance of GA risks is at times necessary.

Altered DNA damage response in Caenorhabditis elegans with impaired poly(ADP-ribose) glycohydrolases genes expression.

Poly(ADP-ribosyl)ation is one of the first cellular responses induced by DNA damage. Poly(ADP-ribose) is rapidly synthesized by nick-sensor poly(ADP-ribose) polymerases, which facilitate DNA repair enzymes to process DNA damage. ADP-ribose polymers are rapidly catabolized into free ADP-ribose units by poly(ADP-ribose) glycohydrolase (PARG). The metabolism of poly(ADP-ribose) is a well-defined biochemical process for which a physiological role in animals is just beginning to emerge. Two Caenorhabditis elegans PARGs, PME-3 and PME-4, have been cloned by our group. The pme-3 gene encodes an enzyme of 89kDa having less than 18% overall identity with human PARG but 42% identity with the PARG signature motif. The pme-4 gene codes for a PARG of 55kDa with approximately 22% overall identity with human PARG and 40% identity with the PARG signature motif. Two alternatively spliced forms of PME-3 were identified with an SL1 splice leader on both forms of the mRNA and were found to be expressed throughout the worm's life cycle. Similarly, pme-4 was shown to be expressed in all developmental stages of the worm. Recombinant enzymes that were expressed in bacteria displayed a PARG activity that may partly account for the PARG activity measured in the total worm extract. Reporter gene analysis of pme-3 and pme-4 using a GFP fusion construct showed that pme-3 and pme-4 are mainly expressed in nerve cells. PME-3 was shown to be nuclear while PME-4 localized to the cytoplasm. Worms with pme-3 and pme-4 expression knocked-down by RNAi showed a significant sensitivity toward ionizing radiations. Taken together, these data provide evidence for a physiological role for PARGs in DNA damage response and survival. It also shows that PARGs are evolutionarily conserved enzymes and that they are part of an ancient cellular response to DNA damage.

Intralesional injection of Tisseel fibrin glue for resection of lymphangiomas and other thin-walled orbital cysts.

PURPOSE: Surgical removal of orbital lymphangiomas is often difficult because the capsule of these lesions is fragile, and, once violated, it tends to collapse, making identification of residual tumor difficult and dissection often incomplete. A surgical technique combining partial controlled decompression of the lesion with intralesional injection of Tisseel fibrin glue is evaluated to determine its effectiveness in resecting the lesion and preventing recurrences. METHODS: This is a retrospective interventional case series. Three young patients, two with lymphangiomas and one with congenital hydrocystoma, underwent surgical resection of their thin-walled cystic lesions of the orbit with the use of intralesional injection of Tisseel fibrin glue. Resolution of the signs and symptoms, complications of the surgery, and recurrence of bleeding are the parameters studied. RESULTS: All 3 patients had improvement of their signs and symptoms. None had complications related to the surgery, and no recurrence of bleeding occurred during the follow-up period. CONCLUSIONS: Our study suggests that this surgical technique with intralesional injection of Tisseel fibrin glue is an effective treatment modality for the resection of lymphangiomas and other orbital thin-walled cystic lesions.

Topoisomerase I amino acid substitutions, Gly185Arg and Asp325Glu, confer camptothecin resistance in Leishmania donovani.

The antitumor compound camptothecin (CPT) is also recognized for its specific activity against Leishmania donovani topoisomerase I (Topo-I). In consequence, defining CPT resistance mechanisms represents an important strategic tool in the acquisition of a better understanding of its mode of action. In the present study, we selected a single highly resistant L. donovani strain termed LdRCPT.160 by stepwise exposure to CPT. Gene sequencing revealed two single nucleotide mutations in the LdRCPT.160 LdTOP1A gene, resulting in two amino acid substitutions (Gly185Arg and Asp325Glu) in the protein. Moreover, these two substitutions observed in the LdTOP1A protein were correlated with a decreased Topo-I DNA relaxation activity in these resistant parasites. Nevertheless, there was no change in the LdTOP1A gene expression level. Interestingly, transfection studies of the LdRCPT.160 LdTOP1A gene in its wild-type counterpart showed that it induced CPT resistance. Site-directed mutagenesis studies demonstrated that, despite a substantial level of resistance conferred by the Gly185Arg and Asp325Glu substitutions separately, both were essential to reach a high-resistance phenotype. Of interest, the amino acid substitutions observed in LdRCPT.160 LdTOP1A protein occurred near the amino acids previously predicted to interact with CPT, providing new insight into the mechanism of CPT molecular action.

Thyroid-associated orbitopathy: a clinicopathologic and therapeutic review.

PURPOSE OF REVIEW: To review the literature related to thyroid-associated orbitopathy and to emphasize recent developments in its pathophysiology, diagnosis, and therapy. Current therapeutic trends and controversies are discussed. RECENT FINDINGS: Expression of thyroid stimulating hormone receptor is highest in the fat and connective tissue of patients with thyroid-associated orbitopathy, where fibroblasts have the potential for adipogenesis. Electrophysiology can now detect subclinical optic neuropathy, and somatostatin-receptor scintigraphy can help justify immunomodulation. Other than steroids, radiotherapy can control inflammation, but its use is controversial. Current trends in orbital decompression are to camouflage incisions and to limit strabismus with balanced decompression, deep lateral wall techniques, fat removal, and onlay implants. Proptosis reductions of 0.9 to 12.5mm are possible by the use of various algorithms. Before or after decompression, botulinum toxin can correct strabismus, intraocular pressure elevation, and retraction. The latter is now also treated with full-thickness blepharotomy. SUMMARY: As knowledge of the pathophysiology of thyroid-associated orbitopathy grows, there is a slow movement from nonspecific and invasive measures to more directed treatments causing less morbidity.