Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) was initially used for locally advanced or inoperable breast cancers. Its extension to early disease has facilitated breast-conserving surgery (BCS). This study investigated the use of NAC in patients registered with the Hong Kong Breast Cancer Registry (HKBCR); it also assessed NAC effectiveness according to rates of pathological complete response (pCR) and BCS. METHODS: Records were retrieved from the HKBCR regarding 13 435 women who had been diagnosed with invasive breast cancer during the period of 2006 to 2017, including 1084 patients who received NAC. RESULTS: The proportion of patients treated with NAC nearly doubled from 5.6% in 2006-2011 to 10.3% in 2012-2017. The increase was most pronounced among patients with stage II or III disease. In terms of biological subtype, substantial increases in the receipt of NAC were evident among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) tumours. The best rates of pCR were observed in patients with HER2-positive (non-luminal) [46.0%] tumours, followed by patients with luminal B (HER2-positive) [29.4%] and triple-negative (29.3%) tumours. After NAC, the rate of BCS was 53.9% in patients with clinical stage IIA disease, compared with 38.2% in patients with pathological stage IIA disease who did not receive NAC. CONCLUSION: The use of NAC in Hong Kong increased from 2006 to 2017. The findings regarding rates of pCR and BCS indicate that NAC is an effective treatment; it should be considered in patients with stage ≥II disease, as well as patients with HER2- positive (non-luminal) or triple-negative breast cancers.

Spatial variation of pneumonia hospitalization risk in Twin Cities metro area, Minnesota.

Fine resolution spatial variability in pneumonia hospitalization may identify correlates with socioeconomic, demographic and environmental factors. We performed a retrospective study within the Fairview Health System network of Minnesota. Patients 2 months of age and older hospitalized with pneumonia between 2011 and 2015 were geocoded to their census block group, and pneumonia hospitalization risk was analyzed in relation to socioeconomic, demographic and environmental factors. Spatial analyses were performed using Esri's ArcGIS software, and multivariate Poisson regression was used. Hospital encounters of 17 840 patients were included in the analysis. Multivariate Poisson regression identified several significant associations, including a 40% increased risk of pneumonia hospitalization among census block groups with large, compared with small, populations of ⩾65 years, a 56% increased risk among census block groups in the bottom (first) quartile of median household income compared to the top (fourth) quartile, a 44% higher risk in the fourth quartile of average nitrogen dioxide emissions compared with the first quartile, and a 47% higher risk in the fourth quartile of average annual solar insolation compared to the first quartile. After adjusting for income, moving from the first to the second quartile of the race/ethnic diversity index resulted in a 21% significantly increased risk of pneumonia hospitalization. In conclusion, the risk of pneumonia hospitalization at the census-block level is associated with age, income, race/ethnic diversity index, air quality, and solar insolation, and varies by region-specific factors. Identifying correlates using fine spatial analysis provides opportunities for targeted prevention and control.

Preventing Infections in Sickle Cell Disease: The Unfinished Business.

While encapsulated bacterial agents, particularly Streptococcus pneumoniae, are recognized as important microbes that are associated with serious illness in hosts with sickle cell disease (SCD), multiple pathogens are implicated in infectious manifestations of SCD. Variations in clinical practice have been an obstacle to the universal implementation of infection preventive management through active, targeted vaccination of these individuals and routine usage of antibiotic prophylaxis. Paradoxically, in low-income settings, there is evidence that SCD also increases the risk for several other infections that warrant additional infection preventive measures. The infection preventive care among patients with SCD in developed countries does not easily translate to the adoption of these recommendations globally, which must take into account the local epidemiology of infections, available vaccines and population-specific vaccine efficacy, environment, health care behaviors, and cultural beliefs, as these are all factors that play a complex role in the manifestation of SCD and the prevention of infectious disease morbidity.

An ecological analysis of pertussis disease in Minnesota, 2009-2013.

The increase in pertussis cases in Minnesota in the last decade has been mainly attributed to the switch from whole cell to acellular pertussis [as part of the diphtheria, tetanus and acellular pertussis vaccine (DTaP)]. It is unclear, however, to what degree community-level risk factors also contribute. Understanding these factors can help inform public health policy-makers about where else to target resources. We performed an ecological analysis within Minnesota to identify risk factors at the county level using a Bayesian Poisson generalized linear areal model to account for spatial dependence. Univariate analyses suggested an association between increased pertussis rates at the county level and white maternal ethnicity, being US born, urban counties and average household size. In the multivariable analysis, the rate of pertussis was 1·79 times greater for urban vs. rural counties and 4·75 times greater for counties with a one-person larger average household size. Pertussis rates in counties with higher (i.e. 4+DTaP) receipt in children were 0·97 times lower. Examining county-level factors associated with varying levels of pertussis may help identify those counties that would most benefit from targeted interventions and increased resource allocation.

Non-tuberculous mycobacterial infection in hospitalized children: a case series.

Non-tuberculous mycobacteria (NTM) illness is an emerging life-threatening infection, and paediatric features have not been well studied. The objective of our study was to review the NTM isolates of hospitalized paediatric patients identified at our institution and to describe the characteristics of these cases. Our retrospective chart review from 2010 to 2013 identified 45 patients with 46 positive NTM cultures. Fifteen (33%) patients had received haematopoietic cell transplant, 13 (29%) had cystic fibrosis, and six (13%) were previously healthy. Twenty-seven (59%) NTM isolates were Mycobacterium chelonae/abscessus, 14 (30%) were M. avium intracellulare, and four (9%) were M. immunogenum. The majority (65%) of cases were community-acquired, and 20 (43%) patients were treated as infection. This case series identified a predominance of M. chelonae/abscessus, and includes a substantial number of haematopoietic cell transplant patients, which reflects the changing spectrum of NTM disease as molecular diagnostics improve and quaternary care facilities provide for a larger immunocompromised population.

Advances and challenges in the management and prevention of community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a common ailment in childhood, and can be associated with significant morbidity and mortality. The introduction of vaccines led to a decline in pneumonia hospitalizations, although gains have been offset by emerging challenges. In addition, appropriate antibiotic management is complicated by the inability and reluctance to perform invasive tests. This review explores the advances made, as well as the new challenges subsequently posed, in the management and prevention of CAP, with emphasis on vaccine-preventable pneumonia, specifically Streptococcus pneumoniae.

A review of tuberculosis-related referrals among children in Ireland.

BACKGROUND: Immigration has been shown to have an increasingly important effect on the epidemiology of tuberculosis (TB) in developed countries. AIM: To review patterns of TB-related referrals to a paediatric infectious diseases clinic. METHODS: Retrospective chart review of TB-related referrals of children attending the Rainbow Clinic at OLCHC between 2003-2005. RESULTS: Forty-seven children were assessed: 18 referred from public health clinics, 5 from general practitioners, and 24 from paediatricians. Most common reason for referral was history of TB exposure (60%). Eighteen (38%) were female, 29 (62%) were male. Thirteen (28%) had latent TB, and 17 (36%) had active disease. Of children with TB disease, 25 (83%) were Caucasian Irish, and the remainder was African. Twenty-five children completed TB treatment and were discharged, and 2 (7%) were lost to follow-up. CONCLUSION: Our study highlights the problem of TB in children, the majority of whom are native to this country.

Ring chromosome 22 resulting in partial monosomy in a mentally retarded boy.

We describe a 7-year-old boy presenting with mental retardation and hyperactivity. Clinical features include microcephaly, hypertelorism, epicanthic eye folds and antimongoloid slant. He also has large ears, large hands and feet, and torticollis. The karyotype was 46, XY, r (22) (p13q13). In situ hybridisation studies with a subtelomeric probe for distal 22q confirmed that the ring was deleted causing partial monosomy of 22q.

Hemodynamic effects of transurethral alprostadil measured by color duplex ultrasonography in men with erectile dysfunction.

PURPOSE: We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography. MATERIALS AND METHODS: Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 microg. alprostadil and intracavernosal injection of 10 microg. alprostadil. RESULTS: A dose of 500 microg. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 microg. alprostadil as measured by duplex ultrasonography in men with erectile dysfunction. Transurethral alprostadil resulted in statistically significant increases in arterial diameter and peak flow velocity comparable to those achieved with intracavernosal injection. End diastolic velocities were higher after transurethral alprostadil than intracavernosal injections. Color ultrasonography following transurethral alprostadil showed arterial and venous hyperemia of the corpus spongiosum and corpora cavernosa. Furthermore, color ultrasonography revealed communicating vessels between the corpus spongiosum and corpora cavernosa following administration of transurethral alprostadil. CONCLUSIONS: The visualization of communicating vessels between the corpus spongiosum and corpora cavernosa after transurethral alprostadil suggests local mechanisms of drug transfer from one to the other. In addition to potential clinical benefits, transurethral alprostadil may be useful to visualize the vascular anatomy of the penis and to test for patient responsiveness to local vasoactive agents.

Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy.

PURPOSE: A retrospective analysis of the MUSE clinical trial was performed to evaluate the efficacy and safety of transurethral alprostadil in patients with erectile dysfunction after radical prostatectomy. MATERIALS AND METHODS: Patients received doses of transurethral alprostadil in the clinic and those for whom a suitable dose was determined were treated at home with active drug or placebo for 3 months. Patients had undergone radical prostatectomy no less than 3 months before study entry. RESULTS: Of the 384 patients in whom radical prostatectomy was identified as a cause of erectile dysfunction 70.3% had an erection believed sufficient for intercourse in the clinic and 57.1% on active medication had sexual intercourse at least once at home. The product of clinic and home success rates (70.3 x 57.1%) was an overall success rate (the likelihood of active treatment to lead to intercourse at home) of 40.1%. The frequency of most adverse effects of radical prostatectomy was comparable to that of other organic etiologies of erectile dysfunction (1,127 patients). The percentage of patients with hypotension in the clinic was lower after radical prostatectomy compared to other erectile dysfunction etiologies (0.8 versus 4.2%, p < 0.001) but the percentage of patients with urethral pain/burning was higher (18.3 versus 10.4%, p = 0.027). No urinary tract infection, fibrosis or priapism occurred in the post-radical prostatectomy patients. CONCLUSIONS: Transurethral alprostadil is a well tolerated and efficacious method of treating erectile dysfunction after radical prostatectomy, although psychological changes associated with cancer and surgery may limit home response. The severe neurovascular deficit associated with prostatectomy neither limits the efficacy of transurethral alprostadil nor increases the risks.

Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations.

PURPOSE: Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder. MATERIALS AND METHODS: In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales. RESULTS: Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination. CONCLUSIONS: Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group.

BACKGROUND: Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. METHODS: Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. RESULTS: During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis. CONCLUSIONS: In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.

A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil.

OBJECTIVES: Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder. METHODS: This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration. RESULTS: Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study. CONCLUSIONS: Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.

Slow continuous hemodialysis for the management of complicated acute renal failure in an intensive care unit.

This paper describes a simple system for the performance of slow continuous hemodialysis (SCHD) as a means of treating difficult and complicated cases of oliguric acute renal failure. The method, which employs access to the circulation via a double-lumen central venous catheter and a BSM 22 blood systems module, can be performed safely in the intensive care unit of a general hospital if closely supervised by a trained nephrologist. The results of treating 16 consecutive cases of complicated acute renal failure in a large general hospital without a hemodialysis unit are described. The method, whose simplicity makes it suitable for intensive care unit nurses without previous hemodialysis training, was not associated with any serious accidents or complications, and was tolerated well by even the most critically ill and hemodynamically unstable patients. The advantages of this approach over more traditional continuous arteriovenous hemofiltration (CAVH) are discussed.

Conformational structure of respiratory mucus studied by laser correlation spectroscopy.

Samples of respiratory mucus were obtained from the trachea of dogs and patients undergoing bronchoscopy. The samples were studied by laser correlation spectroscopy. The autocorrelation function of laser light scattered by both human and canine respiratory mucus was a single exponential in thick mucus or a double exponential in thin watery mucus. This finding suggests that, as in the case of uterine cervical mucus, the molecular structure of respiratory mucus is an ensemble of entangled, randomly-coiled glycoproteins forming a loose network of variable density rather than a covalently cross-linked molecular network as proposed in earlier studies.

Flow permeation analysis of bovine cervical mucus.

Geometrical properties of the microstructure of whole bovine cervical mucus were studied. An experimental technique was developed for measuring the flow of fluid through the mucus microstructure in response to application or a prescribed external pressure gradient. The data obtained were analyzed in conjunction with a mathematical model of the hydrodynamics of the flow-permeation process. The sizes of typical interstices within the microstructure were calculated to be of the order of 1 micrometer, with typical macromolecular filament diameters being of the order of 100 A. These dimensions were interpreted as representative of an equivalent network giving rise to measured flow permeability. The values of filament size showed a strong experimental correlation with the solids content of the mucus.