Ten-year refractive and visual outcomes of intraocular lens implantation in infants with congenital cataract.

INTRODUCTION: There is no consensus regarding optimal target refraction after intraocular lens implantation in infants. This study aimed to clarify relationships of initial postoperative refraction with long-term refractive and visual outcomes. METHODS: This retrospective review included 14 infants (22 eyes) who underwent unilateral or bilateral cataract extraction and primary intraocular lens implantation before the age of 1 year. All infants had ≥10 years of follow-up. RESULTS: All eyes exhibited myopic shift over a mean follow-up period of 15.9 ± 2.8 years. The greatest myopic shift occurred in the first postoperative year (mean=-5.39 ± +3.50 dioptres [D]), but smaller amounts continued beyond the tenth year (mean=-2.64 ± +2.02 D between 10 years postoperatively and last follow-up). Total myopic shift at 10 years ranged from -21.88 to -3.75 D (mean=-11.62 ± +5.14 D). Younger age at operation was correlated with larger myopic shifts at 1 year (P=0.025) and 10 years (P=0.006) postoperatively. Immediate postoperative refraction was a predictor of spherical equivalent refraction at 1 year (P=0.015) but not at 10 years (P=0.116). Immediate postoperative refraction was negatively correlated with final best-corrected visual acuity (BCVA) (P=0.018). Immediate postoperative refraction of ≥+7.00 D was correlated with worse final BCVA (P=0.029). CONCLUSION: Considerable variation in myopic shift hinders the prediction of long-term refractive outcomes in individual patients. When selecting target refraction in infants, low to moderate hyperopia (<+7.00 D) should be considered to balance the avoidance of high myopia in adulthood with the risk of worse long-term visual acuity related to high postoperative hyperopia.

Oct4 is epigenetically regulated by methylation in normal placenta and gestational trophoblastic disease.

Oct4 is a transcription factor that plays a crucial role in maintaining pluripotency of embryonic stem cells. Down-regulation of Oct4 is associated with the differentiation of trophectoderm cell lineage, from which the normal placenta derives. We investigated the methylation and expression status of Oct4 in normal placenta and gestational trophoblastic disease (GTD) as attempts to investigate the role of Oct4 in the pathogenesis of GTD. By methylation-specific PCR, we observed both methylated and unmethylated Oct4 alleles in all 25 first trimester and 10 term placentas while 33% (18/54) of hydatidiform moles, and two choriocarcinoma cell line (JEG3 and JAR), only displayed methylated Oct4 allele. By quantitative TaqMan real-time PCR, Oct4 mRNA was significantly reduced in hydatidiform moles (P=0.04), JEG3 and JAR (P=0.024) when compared with normal placentas. Oct4 methylation was significantly correlated with Oct4 mRNA expression in placenta and GTD (P=0.012). Hypermethylation in minimal promoter and exon 1 region of Oct4 were confirmed in JEG3 and JAR by bisulfite genomic sequencing. The Oct4 mRNA expression in JEG3 and JAR increased after treatment with 5-aza-2'-deoxycytidine and/or trichostatin A. Our findings suggest that Oct4 is down-regulated by hypermethylation in normal placenta and GTD and such process is important in pathogenesis of GTD.

Activated Stat3 expression in gestational trophoblastic disease: correlation with clinicopathological parameters and apoptotic indices.

AIMS: To assess the expression profile of the activated form of signal transducer and activator of transcription (Stat)3 in gestational trophoblastic disease (GTD) and correlate the findings with clinicopathological parameters. METHODS AND RESULTS: By immunohistochemistry, both cytoplasmic and nuclear expression of p-Stat3-Ser(727) was demonstrated in 88 trophoblastic tissues, including placentas and GTD. Nuclear immunoreactivity of p-Stat3-Ser(727) was significantly higher in hydatidiform mole (HM) (P < 0.001) and choriocarcinoma (P = 0.009) when compared with normal placentas. Placental site trophoblastic tumours (PSTT) and epithelioid trophoblastic tumours (ETT) also demonstrated higher nuclear p-Stat3-Ser(727) expression than their normal trophoblast counterparts. Higher p-Stat3-Ser(727) expression was confirmed in choriocarcinoma cell lines, JEG-3 and JAR, than in a normal trophoblast cell line, with both nuclear and cytoplasmic fractions demonstrated by immunoblotting. Spontaneously regressed HM showed significantly increased nuclear and cytoplasmic p-Stat3-Ser(727) immunoreactivity over those that developed gestational trophoblastic neoplasia (GTN) (P = 0.013, P = 0.039). There was a significant positive and inverse correlation between nuclear p-Stat3-Ser(727) immunoreactivity and apoptotic indices [terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling and M30 CytoDeath antibody] (P = 0.001, P < 0.001, Spearman's rho test) and Bcl-2 expression (P = 0.034), respectively. CONCLUSIONS: p-Stat3-Ser(727) plays a role in the pathogenesis of GTD, probably through the regulation of apoptosis. p-Stat3-Ser(727) immunoreactivity is a potential marker in predicting GTN in HM.

Botulinum toxin as an initial therapy for management of sixth nerve palsies caused by nasopharyngeal carcinomas.

PurposeThe purpose of this study is to evaluate the efficacy and safety of botulinum toxin injection as a primary treatment for strabismus in a cohort of patients with nasopharyngeal carcinoma (NPC)-related chronic sixth nerve palsy.Patients and methodsWe retrospectively reviewed all cases of NPC-related sixth nerve palsy receiving botulinum toxin injection in the Hong Kong Eye Hospital between January 2009 and January 2016. Only cases with diplopia for at least 6 months; and failed a trial of Fresnel prism therapy were recruited. We excluded cases with prior strabismus surgery and multiple cranial nerve palsies. Patients were offered botulinum toxin injection as primary treatment for their strabismus and were given further injections or offered surgery if diplopia persisted. Success with botulinum toxin was defined as a final distant orthophoria of <15 PD in primary gaze, no diplopia in primary position, and no head turn, as measured 6 months after the last injection, without requiring a second treatment.ResultsA total of 25 patients were included in the study. All patients received concurrent chemo-radiotherapy for NPC. There was a statistically significant reduction in the mean deviation at distant after the last injection compared to that at presentation (P<0.001, Wilcoxin signed rank test). Overall, 7 patients (28%) achieved clinical success and 15 patients (64%) remained diplopia-free by repeated botulinum toxin injections alone. Nine patients went on to receive definitive surgery and all achieved good ocular alignment after surgery. Transient ptosis or vertical deviation was seen in 7 patients, which resolved within 3 months and no serious complications arose from the treatment in our series.ConclusionsBotulinum toxin injection is a relatively less-invasive alternative to surgery that can be done under a topical anesthesia setting, which improves patient's quality of life via reduction in diplopia. It is a recommendable initial option in patients with chronic nerve palsies who may have higher risks associated with strabismus surgery.

Long-term outcomes of punch punctoplasty with Kelly punch and review of literature.

PurposeTo report long-term outcomes of punch punctoplasty utilizing the Kelly punch and to compare the results with other described methods of punctoplasty in literature.Patients and methodsA retrospective, non-comparative interventional case series of patients who underwent punch punctoplasty at the Hong Kong Eye Hospital over an 8-year period. A standard Kelly Descemet's membrane punch was utilized for punctal enlargement in all cases. Patient records and their operative records were reviewed. Anatomical success was defined by well-patent puncta on follow-up. Functional success was considered complete if tearing resolved completely postop and partial if residual tearing remained despite patent puncta and nasolacrimal drainage system. An OVID MEDLINE review was performed to compare success rates of various punctoplasty surgeries in literature.ResultsIn all, 101 punch punctoplasties from 50 patients were performed between January 2008 to January 2016. At a mean follow-up of 34 months (range: 6-86 months), the anatomical success rate was 94% (95 out of 101 puncta), whereas functional success was 92% (54 out of 59 eyes). Two cases experienced postop dry eyes; otherwise no major complication was observed.ConclusionPunch punctoplasty via the readily available Kelly punch is a simple, minimally invasive procedure that demonstrates high anatomical and functional success as a sole primary treatment for simple punctal stenosis.

The hot-spot p53R172H mutant promotes formation of giant spermatogonia triggered by DNA damage.

Overexpression of mutant p53 is a common finding in most cancers but testicular tumours accumulate wild-type p53 (wtp53). In contrast to the accepted concept that p53 homozygous mutant mice do not accumulate mutant p53 in normal cells, our study on a mutant p53 mouse model of Li-Fraumeni syndrome harbouring the hot-spot p53R172H mutation described an elevated level of mutant p53 in non-cancerous mouse tissues. Here we use detailed immunohistochemical analysis to document the expression of p53R172H in mouse testis. In developing and adult testes, p53R172H was expressed in gonocytes, type A, Int, B spermatogonia as well as in pre-Sertoli cells and Leydig cells but was undetectable in spermatocytes and spermatids. A similar staining pattern was demonstrated for wtp53. However, the intensity of wtp53 staining was generally weaker than that of p53R172H, which indicates that the expression of p53R172H can be a surrogate marker of p53 gene transcription. Comparing the responses of wtp53 and p53R172H to irradiation, we found persistent DNA double-strand breaks in p53R172H testes and the formation of giant spermatogonia (GSG) following persistent DNA damage in p53R172H and p53-null mice. Strikingly, we found that p53R172H promotes spontaneous formation of GSG in non-stressed p53R172H ageing mice. Two types of GSG: Viable and Degenerative GSG were defined. We elucidate the factors involved in the formation of GSG: the loss of p53 function is a requirement for the formation of GSG whereas DNA damage acts as a promoting trigger. The formation of GSG does not translate to higher efficacy of testicular tumorigenesis arising from mutant p53 cells, which might be due to the presence of delayed-onset of p53-independent apoptosis.

Clinical features and prognostic factors of Klebsiella endophthalmitis-10-year experience in an endemic region.

AimsTo identify the clinical features and prognostic factors of endogenous endophthalmitis caused by Klebsiella pneumoniae.MethodsThis is a retrospective case series of all patients with Klebsiella endophthalmitis managed from January 2006 to December 2015 by Kowloon East Ophthalmic Service. Statistical analysis involved hypothesis testing on the SPSS 18.0 software (SPSS). A significance level of P<0.05 was taken.ResultsIn the 10-year period, K. pneumoniae accounted for 19 out of 39 cases of endogenous endophthalmitis (48.7%). The mean age of patients was 67.9 years. Bilateral involvement occurred in five patients (26.3%). More than half of the patients (10/19, 52.6%) had underlying diabetes mellitus. Most patients had concurrent liver abscess (18/19, 94.74%). Ten patients (52.6%) had disseminated intravascular coagulopathy. Eight patients (42.1%) were in shock. The overall mortality was 21.1% (4/19). Septic shock was associated with a significantly higher mortality (50.0 vs 0%, P=0.018). Among the 15 survivors, nine patients (60.0%) required evisceration and three patients (20.0%) had no light perception in an involved eye. Eyes with diffuse posterior involvement were less likely to have a final visual acuity of logMAR 0.30 or better than those with focal posterior involvement (4.76 vs 100% 4.76%, P=0.002). Patients with hypopyon were more likely to require evisceration (85.71 vs 25.00%, P=0.02).ConclusionsKlebsiella endophthalmitis is associated with a high incidence of diabetes mellitus and liver abscess. Prognosis remains poor. Universal ocular screening and systemic control in patients with Klebsiella sepsis are recommended.

Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant.

Extracellular regulated kinase 5 (ERK5) is an unusually large member of the MAP kinase family of signaling molecules that plays an important role in cellular proliferation, differentiation and survival. Recently, three transcriptional variants of murine Erk5 were described (mErk5-a, -b and -c) that result from alternate splicing across introns 1 and/or 2, the net effect of which is translation of a peptide that lacks the kinase domain. It has been demonstrated that expression of mErk5-b and -c impinge on the function of the full length mErk5 protein product via a dominant negative effect. Here, we report the identification of another murine Erk5 splice variant and the orthologous human transcript that arise due to alternate splicing of intron 4. Failure to splice out intron 4 introduces a premature in-frame stop codon that directs translation of a peptide lacking the nuclear localization signal (NLS) and proline-rich region (PR). Experimental characterization demonstrated that like mERK5, mERK5-T becomes phosphorylated by co-expression with a constitutively active mMEK5 (mMEK5DD), and is able to coimmunoprecipitate with both itself and mERK5. Unlike mERK5, however, activated ERK5-T is unable to translocate from the cytoplasm to the nucleus in HeLaS3 cells, causing the retention of active mERK5 in the cytoplasm. Taken together with previous reports of domain content modification of ERK5 via alternate splicing, these observations add to the suggestion that regulation of ERK5 signaling may be mediated, at least in part, at the level of RNA processing.

An outbreak of Pseudomonas aeruginosa related to contaminated urodynamic equipment.

Investigation of an outbreak of multiresistant Pseudomonas aeruginosa urinary tract infections within our hospital identified the urodynamic laboratory as the point source. Disinfection procedures were inadequate, and transducers designated for single-patient use were used repeatedly and subsequently became contaminated. These improper procedures were part of a cost-containment effort.

The effect of respirator training on the ability of healthcare workers to pass a qualitative fit test.

OBJECTIVES: To determine the effect of different methods of training on the ability of hospital workers to wear respirators and pass a qualitative fit test, and to compare the direct cost of the training. DESIGN: 179 hospital employees were recruited for study and were stratified into three groups based on the type of training they received in the use of respirators. Employees in Group A received one-on-one training by the hospital's industrial hygienist and were fit tested as part of this training. Employees in Group B received classroom instruction and demonstration by infection control nurses in the proper use of respirators, but were not fit tested as part of training. Employees in Group C received no formal training. Each participant in our study underwent a subsequent qualitative fit test using irritant smoke to check for the employee's ability to adjust correctly the fit and seal of the respirator. The direct cost of each method of training was determined by accounting for the cost of trainers and the cost of employee-hours lost during training. SETTING: 775-bed Veterans' Affairs hospital. RESULTS: 94% of Group A participants (49 of 52) passed the qualitative fit test, compared to 91% of Group B participants (58 of 64) and 79% of Group C participants (50 of 63; P = .036, 2 x 3 chi-square). Group A had a significantly higher pass rate than Group C (P = .043), but Group B did not differ significantly from Group A or Group C. Location or professional status did not affect pass rate, but prior experience wearing respirators did. When the study groups were compared after stratifying for prior experience, we found no difference in pass rates, except when Groups A and B (those with any training) were combined and compared with Group C (107 of 116 versus 50 of 63, P = .05, Mantel-Haenszel chi-square). We estimate that the method of training involving individual instruction followed by fit testing took 20 minutes per employee to complete, compared to 10 minutes per six employee class for the method of classroom demonstration. The difference in direct cost between the two methods, applied to the training of 1,200 employees at our hospital, would be approximately $19,000 per year. CONCLUSION: Our study indicates that training in the proper use of respirators is important, but the method of training may not be, as the two methods we evaluated were nearly equivalent in their pass rates on fit testing (94% versus 91%). Fit testing as part of training may have enhanced the performance of our participants marginally, but was more time consuming and accounted for most of the excess cost.

An analysis of blood and body fluid exposures sustained by house officers, medical students, and nursing personnel on acute-care general medical wards: a prospective study.

OBJECTIVE: To prospectively examine the epidemiology of blood and body fluid exposures sustained by medicine housestaff, medical school students, registered nurses (RNs), licensed practical nurses (LPNs), and nurses' aides (NAs) on general medicine wards and to define problem areas that may be amenable to change. DESIGN: Daily data collection during 9 months using a self-reporting questionnaire. SETTING: General medical wards in 2 tertiary referral hospitals. PARTICIPANTS: Medicine housestaff/students and nursing personnel. RESULTS: Physicians reported 644 exposures, of which 98 (15.2%), 296 (46.0%), and 250 (38.8%) were sustained by medicine residents, interns, and students, respectively. Blood contact occurred with 591 (91.8%) exposures. For physicians, 575 (89.3%) exposures occurred during venipuncture, intravenous catheter manipulation, and arterial punctures. Interns and students most commonly incurred exposures during venipunctures and intravenous manipulations; residents commonly were exposed during emergent intravenous catheter placements. Five-hundred-twenty-two (81%) exposures occurred between 7 A.M. and 7 P.M. During 524 (81.4%) exposures, physicians were not using barrier devices. Nurses reported 235 exposures, of which 140 (59.6%), 23 (9.8%), and 72 (30.6%) were sustained by RNs, LPNs, and NAs, respectively. RN exposures commonly occurred during intravenous manipulations and glucometer fingersticks. LPNs and NAs incurred a higher percentage of exposures during nonprocedural patient care. Blood contact and wound drainage accounted for 167 (71.1%) and 31 (13.2%) exposures, respectively. CONCLUSIONS: Exposures to blood and body fluids frequently are incurred by healthcare workers on general medical wards. Efforts to reduce these exposures should be directed not only at improving procedural skills of healthcare workers for venipunctures, intravenous catheter insertions, and glucometer fingersticks, but also in increasing barrier use during procedural and nonprocedural tasks.

Do protective devices prevent needlestick injuries among health care workers?

OBJECTIVES: To determine the effectiveness and direct of two protective devices-a shielded 3 ml safety syringe (Safety-Lok; Becton Dickinson and Co., Becton Dickinson Division, Franklin Lakes, N.J.) and the components of a needleless IV system (InterLink; Baxter Healthcare Corp., Deerfield, Ill.)--in preventing needlestick injuries to health care workers. DESIGN: Twelve-month prospective, controlled, before-and-after trial with a standardized questionnaire to monitor needlestick injury rates. SETTING: Six hospital inpatient units, consisting of three medical units, two surgical units (all of which were similar in patient census, acuity, and frequency of needlesticks), and a surgical-trauma intensive care unit, at a 900-bed urban university medical center. PARTICIPANTS: All nursing personnel, including registered nurses, licensed practical nurses, nursing aides, and students, as well as medical teams consisting of an attending physician, resident physician, interns, and medical students on the study units. INTERVENTION: After a 6-month prospective surveillance period, the protective devices were randomly introduced to four of the chosen study units and to the surgical-trauma intensive care unit. RESULTS: Forty-seven needlesticks were reported throughout the entire study period, 33 in the 6 months before and 14 in the 6 months after the introduction of the protective devices. Nursing staff members who were using hollow-bore needles and manipulating intravenous lines accounted for the greatest number of needlestick injuries in the pre-intervention period. The overall rate of needlestick injury was reduced by 61%, from 0.785 to 0.303 needlestick injuries per 1000 health care worker-days after the introduction of the protective devices (relative risk = 1.958; 95% confidence interval, 1.012 to 3.790; p = 0.046). Needlestick injury rates associated with intravenous line manipulation, procedures with 3 ml syringes, and sharps disposal were reduced by 50%; however, reductions in these subcategories were not statistically significant. No seroconversions to HIV-1 or hepatitis B virus seropositivity occurred among those with needlestick injuries. The direct cost for each needlestick prevented was $789. CONCLUSIONS: Despite an overall reduction in needlestick injury rates, no statistically significant reductions could be directly attributed to the protective devices. These devices are associated with a significant increase in cost compared with conventional devices. Further studies must be concurrently controlled to establish the effectiveness of these devices.

Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only.

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.

Prostatic fluid analysis in spinal-cord-injured patients with recurrent urinary tract infections.

OBJECTIVE: Recurrent urinary tract infections are common in spinal-cord-injured patients. Our study was designed to evaluate the association of bacteria colony counts, white blood cell (WBC) count, and antibody-coated bacteria analyzed in urethral and prostatic samples in hospitalized spinal-cord-injured patients with recurrent urinary tract infections. METHODS: Thirty-three patients were studied and 4 noninfected patients served as controls; 17 patients were paraplegic and 20 were quadriplegic. Mean patient age was 34.8 years and mean follow-up period was ninety-three days. During the surveillance period, 19 of the 33 patients had relapsing infections (same organism), while 14 had reinfections (new organism). A modified Foley catheter was used to seal the bladder neck, so that urethral and prostatic samples could be obtained. RESULTS: Bacteria colony counts and WBC counts did not correlate with relapsing infection. However, significantly more patients with relapsing infection (8/19) had antibody-coated bacteria in their prostatic fluid than patients with reinfection (1/13) (P < 0.05). CONCLUSIONS: The presence of antibody-coated bacteria in prostatic fluid is associated with relapsing urinary tract infections and not with reinfection.

Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers.

Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.

Lower extremity amputation prevention in Singapore: economic analysis of results.

INTRODUCTION: The aim of the study was to determine the cost-effectiveness of the Lower Extremity Amputation Prevention (LEAP) strategy in comparison to standard clinical practice for treating patients with critical limb ischaemia (CLI). METHODS: A retrospective cost-effectiveness analysis of the LEAP programme relative to pre-LEAP practice was performed from the perspective of Singapore hospitals. The cost incorporated in the analysis included direct medical costs incurred during the admission. Outcomes included the number of amputations, number of deaths and length of hospital stay after the initial treatment. RESULTS: During the study period, the LEAP group had a lower amputation rate (29 percent versus 76 percent, p-value is 0.00001), lower related death rate (one percent versus 19 percent, p-value is 0.00001) and fewer in-hospital days per patient (17.8 days versus 23.16 days, p-value is 0.048) as compared to the standard clinical practice group. The implementation of the LEAP strategy generated cost savings of S$2,566 per patient during admission when compared with the pre-LEAP approach. The results were robust to variations in input parameters. CONCLUSION: The LEAP strategy dominated standard practice in the management of patients with diabetes mellitus and CLI. The implementation of the LEAP strategy significantly improved patient outcomes and reduced hospital costs.