COVID-19 Virus and Vaccination Attitudes among Healthcare Workers in Michigan: A Cross-Sectional Study.

BACKGROUND: Defining the characteristics of healthcare worker (HCW) attitudes toward the coronavirus disease 2019 (COVID-19) vaccine can provide insights into vaccine hesitancy. This study's goal is to determine HCWs' attitudes regarding the COVID-19 vaccination and reasons for vaccine hesitancy. METHODS: This cross-sectional study surveyed HCWs working in institutions in Saginaw, Sanilac, and Wayne counties in Michigan (N = 120) using tipping-scale questions. Analysis of variance and t-test were used to measure HCWs' attitudes toward the COVID-19 virus and vaccines. RESULTS: Most HCWs received (95.9%) and recommended (98.3%) a COVID-19 vaccine. The top three factors that HCWs cited for recommending a COVID-19 vaccine were: (1) efficacy of the vaccine, (2) current exposure to patients with active COVID-19 infection and risk of virus spread, and (3) safety of vaccine and long-term follow-up. Female HCWs or HCWs aged 25-54 years were more concerned about contracting COVID-19. Physicians or HCWs aged 55-64 were less concerned regarding the effectiveness and side effects of the vaccine. CONCLUSIONS: Gender, age, ethnicity, provider type, and medical specialty showed statistically significant differences among COVID-19 attitudes. Focusing educational efforts on HCW demographics who are more likely to have negative attitudes can potentially decrease vaccine hesitancy.

The impact of educational interventions on COVID-19 and vaccination attitudes among patients in Michigan: A prospective study.

Background: Mass vaccination serves as an effective strategy to combat the COVID-19 pandemic. Vaccine hesitancy is a recognized impediment to achieving a vaccination rate necessary to protect communities. However, solutions and interventions to address this issue are limited by a lack of prior research. Methods: Over 200 patients from 18 Michigan counties participated in this study. Each participant received an initial survey, including demographical questions and knowledge and opinion questions regarding COVID-19 and vaccines. Participants were randomly assigned an educational intervention in either video or infographic format. Patients received a post-survey to assess changes in knowledge and attitudes. Paired sample t-tests and ANOVA were used to measure the effectiveness of the educational interventions. Participants also elected to complete a 3-month follow-up survey. Results: Patients showed increased knowledge after the educational intervention in six out of seven COVID-19 topics (p < 0.005). There was increased vaccine acceptance after the intervention but no difference in the effectiveness between the two intervention modalities. Post-intervention, more patients believed in CDC recommendations (p = 0.005), trusted the vaccine (p = 0.001), believed the vaccines had adequate testing (p = 0.019), recognized prior mistreatment in the medical care system (p = 0.005), agreed that a source they trust told them to receive a vaccine (p = 0.015), and were worried about taking time off of work to get a vaccine (p = 0.023). Additionally, post-intervention, patients were less concerned about mild reactions of the virus (p = 0.005), the rapid development of the vaccines (p < 0.001), and vaccine side effects (p = 0.031). Data demonstrated that attitude and knowledge improved when comparing pre-educational intervention to follow-up but decreased from post-intervention to follow-up. Conclusion: The findings illustrate that educational interventions improved COVID-19 and vaccine knowledge among patients and that the knowledge was retained. Educational interventions serve as powerful tools to increase knowledge within communities and address negative views on vaccination. Interventions should be continually utilized to reinforce information within communities to improve vaccination rates.

Comparative admission rates and infection severity of COVID-19 among unvaccinated and vaccinated patients.

Vaccination efforts have limited the burden of the pandemic caused by the coronavirus disease 2019 (COVID-19) with substantial evidence showing reduced hospitalization rates among vaccinated populations. However, few studies have explored correlations between vaccination status and inpatient COVID-19 outcomes. This observational case-control study involved a retrospective chart review of adult patients hospitalized for COVID-19 infection at a medium-sized hospital in Central Michigan between May 1, 2021 and September 30, 2021. Unadjusted analyses involved t-tests and chi-square tests followed by adjusted analyses using binary logistic and linear regression models. Of the 192 screened patients, 171 subjects met the inclusion criteria. Vaccinated patients were significantly older (71.09 vs 57.45, p < 0.001), more likely to identify as white (89.4% vs 66.9%, p = 0.026), and had a lower baseline 10-year survival rate predicted by the Charlson Comorbidity Index (42% vs 69%, p < 0.001) compared to unvaccinated patients. Common symptoms between both groups included shortness of breath (50%), malaise (23%-37%), cough (28%-32%), and fever or chills (25%). Upon matching, adjusted analysis showed significantly higher rates of remdesivir administration to unvaccinated patients (41.3% vs 13.3%, odds ratio (OR): 4.63, 90% confidence interval (CI): 1.98-11.31). Despite higher intensive care unit admission rates among unvaccinated patients (39.1% vs 23.9%, OR: 1.83, 90% CI: 0.74-4.64), this difference did not reach statistical significance. Accordingly, immunization status strongly correlates with patient demographics and differences in inpatient treatment. Larger studies are needed to further assess the vaccine's impact on inpatient outcomes outside of our community.

CMV proctitis: a rare disease presentation in a young and immunocompetent man.

A young adult man presented to an outlying emergency department with a sore throat, fever and chills. Upon failure of symptomatic management and a course of amoxicillin, he developed rectal pain and loose stools. Despite outpatient doxycycline treatment for presumed chlamydial proctitis, he developed worsening rectal pain and bloody stools. Results on abdominal and pelvic CT were consistent with proctitis. His symptoms worsened despite added metronidazole for bacterial proctitis. Workup revealed an elevated erythrocyte sedimentation rate, C reactive protein and calprotectin, suggestive of a diagnosis of inflammatory bowel disease (IBD). A colonoscopy revealed proximal tightness of the rectum, and pathology reported features suggestive of IBD. He was treated with prednisone and mesalamine. However, immunostaining positive for cytomegalovirus (CMV) confirmed a diagnosis of tissue-invasive CMV proctitis. This was further supported by serological testing for CMV consistent with a diagnosis of CMV proctitis preceded by a primary CMV infection of the pharynx.

A Review of the Clinical Utilization of Oral Antibacterial Therapy in the Treatment of Bone Infections in Adults.

Chronic osteomyelitis in adults is managed with prolonged courses of intravenous antibiotics in conjunction with surgical debridement of necrotic bone. Over the past 40 years, there has been no paradigm shift in this approach, as randomized controlled trials of this standard of care compared to alternatives such as prolonged oral antibiotics are scarce. However, there have been many small trials, case reports, and review papers evaluating the effectiveness of oral treatment for chronic osteomyelitis. The oral route for infections requiring prolonged treatment is intuitively and practically more favorable due to several advantages, the most important of which is the avoidance of long-term IV antimicrobial therapy with its complications, inconvenience, and cost. In this paper, we review the literature evaluating oral antibiotic therapy in the management of chronic bone infections since 1975. The majority of osteomyelitis infections are caused by Staphylococcus aureus, hence we focus on its treatment using oral antibiotics; however, we also emphasize subpopulations of patients with diabetes, implanted hardware, and with less common bacterial organisms. The primary objective of this review is to promulgate clinical recommendations on the use of oral antibiotics in bone infections in the context of initial therapy, transition from intravenous therapy, and the role of chronic suppression. The secondary objective is to summarize current knowledge of the specific oral antimicrobial agents that are commonly utilized, together with a synopsis of the available literature pertaining to their pharmacokinetic/pharmacodynamic properties and duration of therapy in bone infection.

The Blood-Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults.

Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for therapy of CNS infections, some with established roles and indications, others with experimental reporting based on case studies or small series. This review delves into the specifics of the commonly utilized antibacterial agents, updating their therapeutic use in CNS infections from the pharmacokinetic and pharmacodynamic perspectives, with a focus on the optimization of dosing and route of administration that have been described to achieve good clinical outcomes. We also provide a concise synopsis regarding the most focused, clinically relevant information as pertains to each class and subclass of antimicrobial therapeutics. CNS infection morbidity and mortality remain high, and aggressive management is critical in ensuring favorable patient outcomes while averting toxicity and upholding patient safety.

The Effect of Infection Precautions on Extended-Spectrum Beta-Lactamase Enterobacteriaceae Colonization Among Nurses in Three Beirut Hospitals.

Background and objective Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are rapidly emerging worldwide. This study aimed to assess the effect of contact precaution (CP) on ESBL-PE-colonization rates among nurses in three hospitals in Beirut, Lebanon, where ESBL is endemic, in order to define the risk factors for colonization. Accordingly, the ongoing use of CP to prevent ESBL-PE transmission to healthy nurses was evaluated. Methods This cross-sectional study was conducted in three hospitals. Hospital 1 required CP, Hospital 2 had recently stopped CP, and Hospital 3 had stopped it three years previously. Questionnaires and stool-collection containers were distributed to all patient care nurses in those three hospitals. The Returned samples were tested using the agar dilution technique. Results A total of 269 out of 733 nurses volunteered to participate; 140 met the inclusion criteria (no recent hospitalization, antibiotic use, or known ESBL-PE colonization) and provided samples. Among them, 15% were ESBL-positive. Compared to nurses from Hospital 3, nurses from Hospital 1 were 59% less likely to be colonized, while nurses from Hospital 2 were 62% more likely to be colonized. Conclusion In hospitals where CP is in place for ESBL-positive patients, ESBL-PE prevalence in nursing staff was significantly lower. Additionally, a work experience of two to four years increased the odds of ESBL-PE colonization in comparison with longer nursing experience. CP may be a justifiable means of protection against ESBL-PE transmission to healthy nurses. The risk factors for colonization were discontinuation of CP and a shorter clinical work experience.

In-hospital outcomes and prevalence of comorbidities in patients with ST-elevation myocardial infarction with and without infective endocarditis: insight from the National Inpatient Sample (2013-2014).

In patients with infective endocarditis (IE), ST-elevation myocardial infarction (STEMI) is an uncommon phenomenon. Due to limited data, we intend to evaluate the clinical outcomes in hospitalized patients with STEMI with and without underlying IE. Mortality and morbidity are exponentially worse in STEMI with concomitant IE when compared with without IE. Patients with primary diagnosis of STEMI with and without IE were identified by querying the Healthcare Cost and Utilization Project database of the National Inpatient Sample for the years 2013 and 2014 based on International Classification of Diseases, Ninth Revision codes. During 2013 and 2014, a total of 117,386 patients were admitted with the principle diagnosis of STEMI, out of whom 305 had comorbid IE. There was a significantly increased in-hospital mortality (27.5% vs 10.8%), length of stay (LOS) (14 days vs 5 days), acute kidney injury (AKI; 44.9% vs 18.7%), stroke (23.6% vs 3%), aortic valve replacement (9.5% vs 0.3%), mitral valve replacement (0.2%-5.2%), sepsis (50% vs 6%) and acute respiratory failure (36.7% vs 16.7%) in patients with STEMI with IE when compared with patients with STEMI and without comorbid IE. STEMI without IE had a higher number of angiographies (58.7% vs 25.9%) and percutaneous coronary interventions (50.7% vs 14.4%) during the hospital course when compared with STEMI with IE. In conclusions, hospitalized patients with STEMI with a concurrent diagnosis of IE are at higher risk of in-hospital mortality, increased LOS, AKI, stroke, valve replacements, and acute respiratory failure.

Pyogenic Liver Abscess and Sepsis Caused by Streptococcus constellatus in the Immunocompetent Host.

Streptococcus constellatus is a member of Streptococcus milleri group which is a subgroup of Viridans streptococci, first described by Guthof in 1956 after being isolated from dental abscesses. S. constellatus, a gram positive, non-sporing, non-motile, catalase negative cocci, is the normal flora of the oropharyngeal, gastrointestinal and urogenital tract. It is not a commonly encountered pathogen but has a propensity to form abscesses and cause bacteremia in the immunocompromised patient. Here, we report a 78-year-old man with sepsis due to Streptococcus constellatus liver abscess. The patient had a history of hypertension, stroke, benign prostatic hyperplasia, vascular dementia and myocardial infarction status post coronary artery bypass grafting. There has been no particular link between any of these conditions to S. constellatus. However, immunocompromised status predisposes to fulminant infection and formation of abscesses. The patient was febrile with a temperature of 99.1°F, blood pressure of 143/73 mmHg and the heart rate (HR) of 98. Labs revealed a leukocytosis of 16.90 K/uL, hemoglobin 11.8 g/dL, hematocrit 35.8%, total bilirubin 1.7 mg/dL, direct bilirubin 1.0 mg/dL, aspartate aminotransferase (AST) 44 IU/L, alanine aminotransferase (ALT) 28 IU/L, alkaline phosphatase (ALKP) 176 IU/L and lactate dehydrogenase (LDH) was 290 IU/L. He was started on intravenous Maxipime and Unasyn which was switched to Rocephin and Clindamycin based on the Infectious disease recommendations. Metronidazole was also started and the serologies were sent for Entamoeba histolytica. Computerized tomography (CT) scan showed an abscess in the right lobe of the liver which was finally drained using an interventional radiology (IR)-guided approach. The cultures from the fluid and blood yielded S. constellatus and thus Metronidazole was discontinued. The patient improved after a few days and the drainage catheter was pulled out and the patient discharged in stable condition.

The effect of an antibiotic stewardship program on tigecycline use in a Tertiary Care Hospital, an intervention study.

BACKGROUND: A drug-oriented antibiotic stewardship intervention targeting tigecycline utilization was launched at Makassed General Hospital, Beirut, Lebanon, in 2016 as a part of a comprehensive Antibiotic Stewardship Program (ASP). In this study, we evaluated the effect of this intervention on changing tigecycline prescription behavior in different types of infections, patient outcome and mortality, along with tigecycline drug use density, when compared to an earlier period before the initiation of ASP. METHODS: This is a retrospective chart review of all adult inpatients who received tigecycline for more than 72 h between Jan-2012 and Dec-2013 [period (P) 1 before ASP] and between Oct-2016 and Dec-2018 [period (P) 2 during ASP]. RESULTS: Tigecycline was administered to 153 patients during P1 and 116 patients during P2. The proportion of patients suffering from cancer, those requiring mechanical ventilation, and those with hemodynamic failure was significantly reduced between P1 and P2. The proportion of patients who received tigecycline for FDA-approved indications increased from 19% during P1 to 78% during P2 (P < 0.001). On the other hand, its use in off-label indications was restricted, including ventilator-associated pneumonia (26.1% in P1, 3.4% in P2, P < 0.001), hospital-acquired pneumonia (19.6% in P1, 5.2% in P2, P = 0.001), sepsis (9.2% in P1, 3% in P2, P = 0.028), and febrile neutropenia (15.7% in P1, 0.9% in P2, P < 0.001). The clinical success rate of tigecycline therapy showed an overall significant increase from 48.4% during P1 to 65.5% during P2 (P = 0.005) in the entire patient population. All-cause mortality in the tigecycline-treated patients decreased from 45.1% during P1 to 20.7% during P2 (P < 0.0001). In general, mean tigecycline consumption decreased by 55% between P1 and P2 (P < 0.0001). CONCLUSION: The drug-oriented ASP intervention targeting tigecycline prescriptions improved its use and patient outcomes, where it helped curb the over-optimistic use of this drug in off-label indications where it is not a suitable treatment option.

Acute Pancreatitis Associated With Hypothermia: An Uncommon Presentation.

Hypothermia is not known as a common cause of acute pancreatitis, although there have been previously reported cases. Herein, we describe a 55-year-old man who presented with acute pancreatitis preceded by hypothermia in the absence of the more traditional causative factors, such as gallstones or alcohol consumption. On arrival to the emergency department, he was found to have a temperature of 84.3°F, consistent with moderate hypothermia, a blood pressure of 84/50 mmHg, and a heart rate of 60 bpm. Serum lipase and amylase levels were 2,225 and 980 U/L, respectively. A CT scan of the abdomen with intravenous (IV) contrast revealed peripancreatic fat stranding, consistent with the diagnosis. No evidence of gallstones or common bile duct dilatation was found. He had also developed acute kidney injury and lactic acidosis consistent with end-organ damage. After appropriate triage, he was admitted to the intensive care unit and supportively managed. An external rewarming strategy with IV fluids and antibiotics resulted in improvement in clinical status. Hypothermia can cause subtle changes in the microvasculature and production of free radicals, which can result in acute pancreatitis. It is important to determine the etiology so that appropriate treatment can be instituted with better outcomes.

The effect of temporary closure and enhanced terminal disinfection using aerosolized hydrogen peroxide of an open-bay intensive care unit on the acquisition of extensively drug-resistant Acinetobacter baumannii.

BACKGROUND: At Makassed Hospital's open-bay intensive care unit (ICU), enhanced terminal disinfection (ETD) using hydrogen peroxide (H2O2) was performed without a predefined schedule in extensively-drug-resistant Acinetobacter baumannii (XDR-AB) outbreaks. In this study, we aimed to check for the value of the temporary closure of the ICU and the use of ETD with aerosolized H2O2 and Ag+ on minimizing the rate of XDR-AB acquisition in patients admitted to the ICU of our facility, which might consequently help us determine the optimal schedule for such procedure in this unit. METHODS: This is a retrospective medical file review of patients admitted to the ICU between January 2016 and May 2018. We divided this period into numerical weeks (NW) after each closure and ETD episode. Risk factors of acquisition (RFA) were determined by comparing the characteristics of patients who acquired XDR-AB to those who didn't. The proportion of patients residing in each NW was included in the RFA analysis. RESULTS: Out of 335 patients, 13% acquired XDR-AB. The overall incidence of XDR-AB acquisition was 14.6 cases/1000 patient days. RFA were XDR-AB contact pressure ≥ 3 days [Odds Ratio (OR) = 9.86, 95% Confidence Interval (CI) (3.65-26.64), P < 0.0001)], mechanical ventilation [OR = 4.99, 95%CI (1.76-14.15), P = 0.002)], and having a wound [OR = 3.72, 95%CI (0.99-13.96), P = 0.05)]. Patients who stayed during NW 7,11 and 14 were at risk of acquisition where the odds significantly increased by 6.5, 9.7 and 14.4 folds respectively (P = 0.03,0.01, and 0.01, respectively). We considered NW 7 as the most suitable time for temporary closure of the ICU and ETD with aerosolized H2O2. CONCLUSION: Contact pressure, mechanical ventilation, and presence of a wound were RFA of XDR-AB. Temporary closure of the ICU with ETD using aerosolized H2O2 decreased the rate of XDR-AB acquisition, yet this effect fades away with time. The ETD was shown to be most efficiently done when repeated every 7 calendar weeks in our open-bay ICU as part of a prevention bundle.

Pre-engraftment infectious complications and patient outcomes after allogeneic hematopoietic cell transplantation: a single-center experience from Lebanon.

BACKGROUND: Infectious complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). They occur variably over different periods, with scant data reported from Lebanon and neighboring countries. In this study, we described the pre-engraftment neutropenic phase, febrile episodes, and peri-transplant medical complications in patients undergoing allo-HCT at a tertiary-care hospital. METHODS: This is a retrospective chart review of patients who underwent allo-HCT between 2007 and 2016 at Makassed General Hospital in Beirut, Lebanon. Data were extracted from medical records, the HCT registry, and medical laboratory logbooks. RESULTS: One hundred and six patients were included, 75% having hematologic malignancies and 13% aplastic anemia. None received antibacterial prophylaxis with fluoroquinolones. Yet from conditioning chemotherapy till the say before HCT, 32% of the patients received broad-spectrum antibiotics (BSA) due to fever or infection. At the day of cell infusion, 41.5% of the patients were on BSA. Neutrophil engraftment failure was recorded in 8% of the patients. The cumulative incidence of pre-engraftment bacteremia and Gram-negative bacteremia was 14.3 and 7.1%, respectively. Aplastic anemia was an independent risk factor for pre-engraftment bacteremia [hazard ratio (HR) = 3.86, 95% confidence interval (CI) (1.29-11.5), P = 0.02]. The cumulative incidence of pre-engraftment pneumonia was 11.2%. Patient age significantly increased the risk of pre-engraftment pneumonia [HR = 12.35, 95% CI (1.27-120.50), P = 0.03]. Six-month post-transplant mortality reached 17% in our cohort. Myelodysplastic syndrome was the only significant parameter increasing the risk of death [HR = 3.40, 95% CI (1.05-10.98), P = 0.04]. CONCLUSION: The cumulative incidence of pre-engraftment bacteremia and pneumonia was 14.3% and 11.2% respectively in this cohort. Aplastic anemia predicted for the occurrence of bacteremia, increasing patient age contributed to the occurrence of pneumonia, and myelodysplastic syndrome increased the risk of death.

The 2018 Lebanese Society of Infectious Diseases and Clinical Microbiology Guidelines for the use of antimicrobial therapy in complicated intra-abdominal infections in the era of antimicrobial resistance.

BACKGROUND: The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) is involved in antimicrobial stewardship. In an attempt at guiding clinicians across Lebanon in regards to the proper use of antimicrobial agents, members of this society are in the process of preparing national guidelines for common infectious diseases, among which are the guidelines for empiric and targeted antimicrobial therapy of complicated intra-abdominal infections (cIAI). The aims of these guidelines are optimizing patient care based on evidence-based literature and local antimicrobial susceptibility data, together with limiting the inappropriate use of antimicrobials thus decreasing the emergence of antimicrobial resistance (AMR) and curtailing on other adverse outcomes. METHODS: Recommendations in these guidelines are adapted from other international guidelines but modeled based on locally derived susceptibility data and on the availability of pharmaceutical and other resources. RESULTS: These guidelines propose antimicrobial therapy of cIAI in adults based on risk factors, site of acquisition of infection, and clinical severity of illness. We recommend using antibiotic therapy targeting third-generation cephalosporin (3GC)-resistant gram negative organisms, with carbapenem sparing as much as possible, for community-acquired infections when the following risk factors exist: prior (within 90 days) exposure to antibiotics, immunocompromised state, recent history of hospitalization or of surgery and invasive procedure all within the preceding 90 days. We also recommend antimicrobial de-escalation strategy after culture results. Prompt and adequate antimicrobial therapy for cIAI reduces morbidity and mortality; however, the duration of therapy should be limited to no more than 4 days when adequate source control is achieved and the patient is clinically stable. The management of acute pancreatitis is conservative, with a role for antibiotic therapy only in specific situations and after microbiological diagnosis. The use of broad-spectrum antimicrobial agents including systemic antifungals and newly approved antibiotics is preferably restricted to infectious diseases specialists. CONCLUSION: These guidelines represent a major step towards initiating a Lebanese national antimicrobial stewardship program. The LSIDCM emphasizes on development of a national AMR surveillance network, in addition to a national antibiogram for cIAI stratified based on the setting (community, hospital, unit-based) that should be frequently updated.

Long-term incidence of symptomatic urolithiasis post-bariatric surgery.

INTRODUCTION: The risk of urolithiasis post-Roux-en-Y gastric bypass (RYGB) surgery is higher when compared to the general population. Calcium and vitamin D supplementation is routinely prescribed to these patients, yet compliance with these supplements is unknown. The aim of this study was to assess the incidence of symptomatic de novo urolithiasis post-RYGB and compliance with calcium and vitamin D supplementation. METHODS: A standardized telephone questionnaire was administered to patients who underwent RYGB between 1996 and 2011. Personal and medical histories were obtained with emphasis on episodes of symptomatic urolithiasis and calcium and vitamin D supplementation. RESULTS: The response rate was 48% with 478 patients completing the telephone questionnaire. After a mean follow-up of 7.0 years (range: 1-15), the incidence of post-RYGB symptomatic urolithiasis was 7.3%, while the rate of de novo symptomatic urolithiasis was 5%. The overall median time to present with symptomatic urolithiasis was 3.1 years, with 3.3 years for de novo stone-formers, and 2.0 years for recurrent stone-formers (p = 0.38). In de novo stone-formers, 33% presented with symptomatic urolithiasis 4 to 14 years postoperatively. Compliance with calcium and vitamin D supplementation was 56% and 51%, respectively. CONCLUSIONS: Despite recall bias and lack of confirmatory imaging studies, a high postoperative incidence of symptomatic urolithiasis was found in a large sample of post-RYGB patients. A third of patients with de novo stones, presented with symptomatic urolithiasis 4 to 14 years postoperatively. Compliance with postoperative calcium and vitamin D supplementation was poor and needs improvement.

Is ex vivo microdissection testicular sperm extraction indicated for infertile men undergoing radical orchiectomy for testicular cancer? Case report and literature review.

OBJECTIVE: To report a case of an infertile man with nonobstructive azoospermia who underwent simultaneous radical orchiectomy for testicular cancer and testicular sperm extraction (TESE) for preservation of fertility. DESIGN: Case report and literature review. SETTING: University teaching hospital. PATIENT(S): A couple being treated for infertility. INTERVENTION(S): Radical orchiectomy with simultaneous TESE. MAIN OUTCOME MEASURE(S): Sperm retrieval, histologic evaluation of archived testicular pathology slides. RESULT(S): We retrieved 20 spermatozoa from the multiple random TESE samples obtained at radical orchiectomy. Histologic evaluation of the archived testicular pathology slides revealed that the testis contained several foci of active spermatogenesis, suggesting that a significantly greater number of spermatozoa would likely have been retrieved had a microdissection TESE been performed instead of the multiple TESEs. CONCLUSION(S): We propose that microdissection TESE should be considered the preferred sperm retrieval technique at the time of radical orchiectomy in men with coexistent nonobstructive azoospermia and testicular cancer.

Claudin-7, -16, and -19 during mouse kidney development.

Members of the claudin family of tight junction proteins are critical for establishing epithelial barriers and for the regulation of paracellular transport. To understand their roles during kidney development, we first performed RT-PCR analyses and determined that 23 claudin family members were expressed in embryonic day (E) 13.5 mouse kidneys. Based on their developmental expression and phenotypes in mouse models, we hypothesized that 3 claudin members could affect nephron formation during kidney development. Using whole mount in situ hybridization and immunohistochemistry, we demonstrated that Claudin-7 (Cldn7) was expressed in the nephric duct, the emerging ureteric bud, and in tubules derived from ureteric bud branching morphogenesis. In contrast, Claudin-16 (Cldn16) and Claudin-19 (Cldn19) were expressed at later stages of kidney development in immature renal tubules that become the Loop of Henle. To determine if a loss of these claudins would perturb kidney development, we examined newborn kidneys from mutant mouse models lacking Cldn7 or Cldn16. In both models, we noted no evidence for any congenital renal malformation and quantification of nephron number did not reveal a decrease in nephron number when compared to wildtype littermates. In summary, Cldn7, Cldn16, and Cldn19 are expressed in different epithelial lineages during kidney development. Mice lacking Cldn7 or Cldn16 do not have defects in de novo nephron formation, and this suggests that these claudins primarily function to regulate paracellular transport in the mature nephron.

Simultaneous bilateral subcutaneous pyelovesical bypass as a salvage procedure in refractory retroperitoneal fibrosis.

Ureteral obstruction causing renal failure is the most common complication associated with retroperitoneal fibrosis (RPF). Initial management includes steroid therapy together with ureteral stenting. When these fail, ureterolysis is the recommended surgical procedure. However, this could be challenging and recurrence is common. The aim of the present case series was to assess the feasibility of inserting simultaneous bilateral subcutaneous pyelovesical bypass grafts (SPBGs) in patients presenting with RPF who had failed initial endourologic/surgical management.

The tight junction protein claudin-3 shows conserved expression in the nephric duct and ureteric bud and promotes tubulogenesis in vitro.

The claudin family of proteins is required for the formation of tight junctions that are contact points between epithelial cells. Although little is known of the cellular events by which epithelial cells of the ureteric bud form tubules and branch, tubule formation is critical for kidney development. We hypothesize that if claudin-3 (Cldn3) is expressed within tight junctions of the ureteric bud, this will affect ureteric bud cell shape and tubule formation. Using transmission electron microscopy, we identified tight junctions within epithelial cells of the ureteric bud. Whole mount in situ hybridization and immunoassays were performed in the mouse and chick and demonstrated that Cldn3 transcript and protein were expressed in the nephric duct, the ureteric bud, and its derivatives at critical time points during tubule formation and branching. Mouse inner medullary collecting duct cells (mIMCD-3) form tubules when seeded in a type I collagen matrix and were found to coexpress CLDN3 and the tight junction marker zonula occludens-1 in the cell membrane. When these cells were stably transfected with Cldn3 fused to the enhanced green fluorescent protein reporter, multiple clones showed a significant increase in tubule formation compared with controls (P < 0.05) due in part to an increase in cell proliferation (P < 0.01). Cldn3 may therefore promote tubule formation and expansion of the ureteric bud epithelium.

Antigen clearance during treatment of disseminated histoplasmosis with itraconazole versus fluconazole in patients with AIDS.

Antifungal treatment reduces the concentration of Histoplasma antigen in blood and urine, supporting a hypothesis that antigen clearance could be used to compare the activity of new agents for treating histoplasmosis. In separate trials in patients with AIDS, clinical response was similar with itraconazole (85%) and fluconazole (74%). Fungal blood cultures at week 4, however, were negative in a significantly higher proportion of patients treated with itraconazole (92.3%) than in those treated with fluconazole (61.9%) (P = 0.017). Baseline antigen concentrations were similar in the two groups: serum, P = 0.7235; and urine, P = 0.1360. After 4 weeks of treatment, the decline in antigen from baseline in serum was similar in the two treatment groups (P = 0.5237), as it was in urine (P = 0.4679). At week 12, the decline in antigen from baseline in serum also was similar in the two groups (P = 0.4911) and in urine (P = 0.2786). More rapid clearance of fungemia suggests that itraconazole is more effective than fluconazole in treating histoplasmosis. This study demonstrates that clearance of fungemia is a better measure of antifungal effect than clearance of antigen.