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.

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.

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.

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.

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.

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.

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.

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.

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.

Impact of hospital care on incidence of bloodstream infection: the evaluation of processes and indicators in infection control study.

The Evaluation of Processes and Indicators in Infection Control (EPIC) study assesses the relationship between hospital care and rates of central venous catheter-associated primary bacteremia in 54 intensive-care units (ICUs) in the United States and 14 other countries. Using ICU rather than the patient as the primary unit of statistical analysis permits evaluation of factors that vary at the ICU level. The design of EPIC can serve as a template for studies investigating the relationship between process and event rates across health-care institutions.

Evidence for direct interaction between Sprouty and Cbl.

Sprouty (SPRY) was first identified in a genetic screen in Drosophila as an antagonist of fibroblast and epidermal growth factor receptors and Sevenless signaling, seemingly by inhibiting the receptor tyrosine kinase (RTK)/Ras/MAPK pathway. To date, four mammalian Sprouty genes have been identified; the primary sequences of the gene products share a well conserved cysteine-rich C-terminal domain with their Drosophila counterpart. The N-terminal regions do not, however, exhibit a large degree of homology. This study was aimed at identifying proteins with which human SPRY2 (hSPRY2) interacts in an attempt to understand the mechanism by which Sprouty proteins exert their down-regulatory effects. Here, we demonstrate that hSPRY2 associates directly with c-Cbl, a known down-regulator of RTK signaling. A short sequence in the N terminus of hSPRY2 was found to bind directly to the Ring finger domain of c-Cbl. Parallel binding was apparent between the Drosophila homologs of Sprouty and Cbl, with cross-species associations occurring at least in vitro. Coexpression of hSPRY2 abrogated an increase in the rate of epidermal growth factor receptor internalization induced by c-Cbl, whereas a mutant hSPRY2 protein unable to bind c-Cbl showed no such effect. Our results suggest that one function of hSPRY2 in signaling processes downstream of RTKs may be to modulate c-Cbl physiological function such as that seen with receptor-mediated endocytosis.

Sprouty proteins are targeted to membrane ruffles upon growth factor receptor tyrosine kinase activation. Identification of a novel translocation domain.

Sprouty (Spry) was first identified in a genetic screen in Drosophila to be an antagonist of fibroblast growth factor and epidermal growth factor (EGF) signaling, seemingly by inhibiting the Ras/MAP kinase pathway. Data base searches lead to the identification and cloning of, to date, four mammalian sprouty genes. The primary sequences of the mammalian sprouty gene products share a well conserved cysteine-rich C-terminal domain with the Drosophila protein. The N-terminal regions, however, do not exhibit significant homology. This study aimed at determining the disposition of Spry proteins in intact cells before and after stimulation of the EGF receptor tyrosine kinase. Full-length or deletion mutants of Spry, tagged at the N termini with the FLAG-epitope, were expressed in COS-1 cells by transient transfection and analyzed by immunofluorescence microscopy before and after EGF stimulation of the cells. In unstimulated cells, the Spry proteins were distributed throughout the cytosol except for human Sprouty2 (hSpry2), which, although generally located in the cytosol, co-localized with microtubules. In all cases, the Spry proteins underwent rapid translocation to membrane ruffles following EGF stimulation. The optimal translocation domain was identified by deletion and immunofluorescence analysis to be a highly conserved 105-amino acid domain in the C-terminal half of the hSpry2 protein. The translocation of this conserved domain, based on hSpry2 data, was independent of the activation of phosphatidylinositol-3 kinase.

Staphylococcus aureus and other bacteremias in hemodialysis patients: antibiotic therapy and surgical removal of access site.

BACKGROUND: Bacteremia is commonplace in patients undergoing hemodialysis since the vascular access site is a ready source of infection. Mortality is notably high. However, uncertainties exist with respect to therapy including indications for surgical removal of vascular access site and duration of therapy. We therefore conducted a large-scale collaborative study of bacteremia in hemodialysis patients in six US academic medical centers to define the epidemiology of such infections and to address issues of management. PATIENTS AND METHODS: We conducted a prospective observational study over 2 years. Severity of illness at onset of bacteremia was defined by objective criteria. Patients were followed for 90 days to assess late complications including endocarditis and mortality. Univariate and multivariate analyses were used to assess risk factors for mortality. RESULTS: Patients experiencing 127 consecutive episodes of bacteremia were enrolled. The most common cause of bacteremia was Staphylococcus aureus (31%), followed by aerobic gram-negative bacilli (28%) and coagulase-negative staphylococci (13%). Polymicrobial bacteremia occurred in 6% of patients. The most frequent focus of infection was the access site for hemodialysis, although urinary tract, gastrointestinal tract and lung were also implicated. Aerobic gram-negative bacilli and enterococci usually originated from the urinary tract. S. aureus was significantly more likely to cause infection of the access site than other bacteria (p = 0.0001). S. aureus endocarditis was diagnosed in two patients who were receiving antibiotic therapy for S. aureus bacteremia. Removal of the infected access site (shunt, fistula, catheter) was performed for 86% of the patients (95% of the intravenous catheters and 80% of the arteriovenous fistulas/shunts). Overall mortality was 33% at 90 days and was significantly associated with severity of illness at onset of antibiotic therapy and age >60 years. Mortality was not significantly different in patients undergoing surgical removal of infected access site versus those treated with antibiotics alone. CONCLUSION: When S. aureus was isolated from the blood, the access site was the most frequent source. Surgical removal of the access site did not have a notable impact on mortality. Until a randomized trial proves otherwise, it appears that surgical removal of the access site can be individualized. Selected patients who are less severely ill (based on objective criteria) can maintain their hemodialysis access site and be treated with 2 weeks of antibiotic therapy.

Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by fibroblast growth factor receptor-1 prevents its binding to Cdc42GAP and Cdc42.

Fibroblast growth factor (FGF) receptor tyrosine kinases are involved in the regulation of cell growth, development, and differentiation in a variety of tissues. To isolate potential signaling molecules in the FGF signaling pathway, we have initiated a yeast two-hybrid screening using the cytosolic domain of FGF receptor-1 (Flg). Here we report the identification of BNIP-2, a previously cloned Bcl-2- and adenovirus E1B-associated protein, as a putative substrate of the receptor. When cotransfected in 293T cells, BNIP-2 was tyrosine-phosphorylated via Flg, but their interaction was transient and could only be seen by "capture" experiments with catalytically inert kinase mutants. When responsive cells were challenged with basic FGF, endogenous tyrosine-phosphorylated BNIP-2 could be precipitated with a BNIP-2 antibody. In addition, the recombinant BNIP-2 expressed in bacteria could be phosphorylated by active Flg in vitro. BNIP-2 shares a region of homology with the noncatalytic domain of Cdc42GAP, a GTPase-activating protein for the small GTP-binding molecule, Cdc42. We show here that BNIP-2 and Cdc42GAP could directly bind to each other and they also compete for the binding to the same target, Cdc42. Unexpectedly, BNIP-2, either produced as a bacterial recombinant protein or expressed in 293T cells, could stimulate the intrinsic GTPase activity of Cdc42. In all cases, tyrosine phosphorylation of BNIP-2 severely impaired its association with Cdc42GAP and its induced GTPase-activating protein-like activity toward Cdc42. These findings should allow us to further characterize the integration of signaling between receptor tyrosine kinases, GTP-binding molecules, and apoptotic pathways.

Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling.

FRS2 is a docker protein that recruits signaling proteins to the plasma membrane in fibroblast growth factor signal transduction. We report here that FRS2 was associated with PKC lambda when Swiss 3T3 cells were stimulated with basic fibroblast growth factor. PKC zeta, the other member of the atypical PKC subfamily, could also bind FRS2. The association between FRS2 and PKC lambda is likely to be direct as shown by yeast two-hybrid analysis. The C-terminal fragments of FRS2 (amino acid residues 300-508) and SNT2 (amino acids 281-492), an isoform bearing 50% identity to FRS2, interacted with PKC lambda at a region (amino acids 240-562) that encompasses the catalytic domain. In vitro kinase assays revealed neither FRS2 nor SNT2 was a substrate of PKC lambda or zeta. Mutation of the alanine residue (Ala-120) to glutamate in the pseudo-substrate region of PKC lambda results in a constitutively active kinase that exhibited more than 2-fold greater binding to FRS2 in vitro than its "closed" wild-type counterpart. Tyrosine phosphorylation of FRS2 did not affect its binding to the constitutively active PKC lambda mutant, suggesting that the activation of PKC lambda is necessary and sufficient for its association with FRS2. It is likely that FRS2 serves as an anchoring protein for targeting activated atypical PKCs to the cell plasma membrane in signaling pathways.

Urinary tract infections in adults.

Urinary tract infections remain a significant cause of morbidity in all age groups. Recent studies have helped to better define the population groups at risk for these infections, as well as the most cost-effective management strategies. Initially, a urinary tract infection should be categorized as complicated or uncomplicated. Further categorization of the infection by clinical syndrome and by host (i.e., acute cystitis in young women, acute pyelonephritis, catheter-related infection, infection in men, asymptomatic bacteriuria in the elderly) helps the physician determine the appropriate diagnostic and management strategies. Uncomplicated urinary tract infections are caused by a predictable group of susceptible organisms. These infections can be empirically treated without the need for urine cultures. The most effective therapy for an uncomplicated infection is a three-day course of trimethoprim-sulfamethoxazole. Complicated infections are diagnosed by quantitative urine cultures and require a more prolonged course of therapy. Asymptomatic bacteriuria rarely requires treatment and is not associated with increased morbidity in elderly patients.