Comparative meta-analysis of host transcriptional response during Streptococcus pneumoniae carriage or infection.

Infection with Streptococcus pneumoniae causes over 150,000 cases of pneumonia annually in the United States alone. We performed a meta-analysis of publicly available RNA-sequencing data to compare the host-specific intracellular transcriptional responses that differ between infection and carriage with S. pneumoniae in humans and mice. We applied an automated preprocessing workflow to collections of publicly available fastq files that were categorized as either of two phenotypes-infection or carriage in humans and mice. We identified the differentially expressed genes and intracellular signaling pathways that changed in host cells during infection or carriage and whether these human phenotypes could be appropriately modeled at the molecular level in mice. Although we observed multiple differentially expressed genes shared among multiple comparisons, we found no overlapping significant signaling pathways between the mouse and human studies in either phenotype. Based on the samples included in this secondary analysis, we identified a minimal number of generalized transcriptional relationships between host infection and carriage phenotypes of S. pneumoniae that were consistently shared between the mouse and human hosts. Our findings suggest that additional controlled datasets in mouse and human carriage or infection models are needed to better understand the underlying mechanism(s) of invasion and pathogenesis. This knowledge could then contribute to the development of improved prophylactics and/or therapeutics against this pathogen.

Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

BACKGROUND: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample. METHODS: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. RESULTS: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. CONCLUSIONS: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

Five-year risk of incident disease following a diagnosis of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS. OBJECTIVE: The objective of this study was to determine the risk of incident disease within 5 years after a new diagnosis of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). METHODS: We conducted a case-control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRSwNP and CRSsNP cases compared to controls using multivariable Cox regression models. RESULTS: CRSsNP (n = 3612) cases were at greater risk (HR, 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41-4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14-3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23-6.16); and hypertension (1.38, 1.19-1.61). CRSwNP (n = 241) cases were at greater risk for obesity than controls (1.74, 1.08-2.80), but CRSwNP was not associated with other diseases. CONCLUSION: The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRSwNP sample size limitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients.

Cystic hygroma/lymphangioma: a rational approach to management.

OBJECTIVE: To outline a rational approach to the management of cystic hygroma based on the authors' experience, the natural history of the disease, and the results of surgical treatment. STUDY DESIGN AND METHODS: A retrospective review of all patients with the diagnosis of lymphangioma or cystic hygroma from 1958 to 2000 was performed. RESULTS: Seventy-four patients were identified with 46 cases confined to the cervicofacial region. Surgical excision was performed on 60 of the 74 cases involving all regions of the body and 34 of the 46 patients with head and neck lesions. The location of the malformation is the most important determinate for surgical success. While surgical excision was the main treatment modality, 11 of 12 untreated patients were noted to improve, with 8 patients showing complete resolution. CONCLUSIONS: In the treatment of lymphangiomas, the physician should be experienced in the management of such lesions, be aware of spontaneous resolution, and recognize the limitations and potential harm of surgery in certain instances.

The CT appearance of thyroglossal duct carcinoma.

BACKGROUND AND PURPOSE: Thyroid carcinoma arising in a thyroglossal duct cyst may be clinically indistinguishable from a benign thyroglossal duct cyst. The preoperative diagnosis of carcinoma, however, can have important implications for surgical planning and postoperative treatment. Our purpose was to describe the CT appearance of thyroglossal duct carcinoma and identify the features that distinguish thyroglossal duct carcinoma from benign thyroglossal duct cysts. METHODS: Retrospective review of the medical records from the University of Pittsburgh Medical Center and Geisinger Medical Center (Danville, Pennsylvania) identified six patients with papillary thyroid carcinoma within the thyroglossal duct who had undergone preoperative CT examinations of the neck. There were two women and four men. Their ages ranged from 14 to 59 years. Three patients underwent contrast-enhanced CT of the neck, and three underwent unenhanced CT. All CT examinations consisted of 3- to 5-mm-thick contiguous axial sections. RESULTS: Each patient had an anterior neck mass with a cystic component. Two of the masses had dense or enhancing mural nodules, two had irregular calcification throughout the mass, and two had dense or enhancing mural nodules with additional foci of calcification. One patient had cervical lymphadenopathy. CONCLUSION: Carcinoma should be considered in thyroglossal duct cysts that have a mural nodule or calcification or both.

Surgical management of localized amyloidosis.

OBJECTIVE: To demonstrate the role of two-dimensional reconstruction images on computed tomography (CT) in the treatment planning for laryngeal amyloidosis. To discuss the treatment for isolated laryngeal amyloidosis and compare the role of endoscopic versus an open surgical approach to management. STUDY DESIGN: Retrospective review. METHODS: The medical records from 1984 to the present with the diagnosis of localized respiratory tract amyloidosis at Geisinger Medical Center were reviewed. RESULTS: Five previously unpublished cases of localized laryngeal amyloidosis were identified with the supraglottic region the major site of involvement. Hoarseness and airway compromise were the presenting symptoms. CT two-dimensional reconstruction imaging was used to evaluate two cases with extensive laryngeal involvement that required an external surgical approach to relieve symptoms. CONCLUSIONS: Localized laryngeal amyloidosis is a rare disease that requires surgical management when symptomatic. CT two-dimensional reconstruction can be helpful in detailing the extent of disease and planning surgery. A lateral external supraglottic approach has been found to be successful in treating patients with large supraglottic masses.

Thyroglossal duct carcinoma: a rational approach to management.

OBJECTIVE: To discuss the authors' experience with thyroglossal duct carcinoma and present a rational approach to the management of this entity. STUDY DESIGN AND METHODS: A retrospective review of the cytopathology and pathology records of all patients with the diagnosis of a thyroglossal duct remnant from 1965 to 1997 was performed. RESULTS: Three cases of papillary thyroglossal duct carcinoma were identified, with one suspected squamous cell carcinoma by needle aspiration. The papillary carcinomas are discussed in detail to illustrate the difficulty encountered in managing the thyroid gland in the setting of a thyroglossal duct carcinoma. Fine-needle aspiration proved effective in making the diagnosis preoperatively. CONCLUSIONS: The authors recommend that a thyroglossal duct cyst with a microscopic focus of papillary carcinoma, without cyst wall invasion, be managed with a Sistrunk procedure. Treatment of all other thyroglossal duct papillary carcinomas should include removal of all thyroid tissue followed by radioactive iodine treatment.

Non-nodal neck masses.

Planar imaging has made significant contributions to the evaluation of patients with non-nodal neck masses. The clinical history, physical examination, and imaging characteristics of these lesions are often complimentary. Yet, planar imaging much more accurately defines the size, location, and extent of these lesions than is revealed on physical examination. The CT and MR characteristics are often sufficiently specific to arrive at the correct preoperative diagnosis in these patients. We present the classical radiographic and clinical features of several non-nodal neck masses.

Phaeochromocytoma in Northern Ireland: a 21 year review.

OBJECTIVE: To report our experience of 41 patients with phaeochromocytoma. DESIGN: Retrospective study. SETTING: Teaching hospital, United Kingdom. SUBJECTS: Forty-one patients who presented with phaeochromocytoma 1970-1991. INTERVENTIONS: Removal of tumour (n = 38). MAIN OUTCOME MEASURES: Mortality, morbidity, and recurrence. RESULTS: Thirty-four patients had sporadic tumours, five had the multiple endocrine neoplasia (MEN) type 2 syndrome, and two had non-MEN familial phaeochromocytoma. Thirty-six patients (88%) presented with symptoms of catecholamine excess, and 37 (90%) were hypertensive. The diagnosis was confirmed biochemically in 37. Tumours were located using computed tomography (n = 26), vascular studies (n = 11), and ultrasonography (n = 3). Thirty-eight patients had their tumours resected, of whom 10 (27%) developed complications. There were no postoperative deaths. Two patients were managed conservatively, and one died before diagnosis. Six patients developed recurrent tumours a mean of five years after the initial operation, and another patient had an inoperable tumour at initial diagnosis; four of these seven died from metastatic disease. Metaiodobenzylguanidine (MIBG) scans were positive in three of the patients who developed recurrences. CONCLUSIONS: Patients with phaeochromocytoma can now be operated on safely but prolonged follow-up is essential.

Pediatric cardiology in the 1990s.

OBJECTIVES: In 1991, all active board-certified pediatric cardiologists were polled by questionnaire to examine the relation of subspecialty training and motivational and satisfaction issues to practice characteristics. BACKGROUND: Previous questionnaires with regard to manpower status and practice characteristics were published in 1967 and 1980. These indicated a field predominantly centered in academic medicine with growth in manpower close to predicted need. METHODS: The questionnaire was mailed to 844 of 884 active board-certified pediatric cardiologists and was returned anonymously by 570, a 68% response rate. RESULTS: Among respondents, the mean year in which fellowship training was completed was 1974. The average length of subspecialty training was 31 months for all respondents and 34 months among those completing training since 1981. Seventy-seven percent of subspecialty training centered on clinical training. Although there has been a slight increase in research training in recent years, only 18 respondents completed > or = 22 months of research training. Respondents devote a mean of 89% of professional hours to subspecialty activities and spend 63% of total hours in clinical care. Total hours, income and procedures were related to site of professional activity. Professional satisfaction was high in the factors considered more important: professional challenge and interaction, clinical resources, career security and clinical autonomy. CONCLUSIONS: The field of pediatric cardiology is a subspecialty centered on patient care and performance of diagnostic and interventional techniques. Professional activities varied according to practice site. Pediatric cardiologists with basic research training and professional activity remain a minority. Satisfaction is high, with greatest satisfaction in professional interactions and least satisfaction with income and free time.

Altered renovascular resistance after spontaneous recovery from hemolytic uremic syndrome.

Twenty-three patients were evaluated from 1-15 (mean 6) years after recovering from an episode of diarrhea-associated associated childhood hemolytic uremic syndrome (DA-HUS). All patients had received only conservative treatment; none had been given experimental, anti-coagulant, or immunological therapies. Follow-up studies included morphologic and duplex Doppler sonograms. Doppler sonography was used to determine the resistive index, a measure of renovascular resistance. Histories and physical examinations revealed no abnormalities. Results of laboratory studies, which included calculated glomerular filtration rates, were all within normal limits, except for one patient with minor urinary abnormalities. Renal sonograms showed no significant abnormalities of kidney length or parenchymal appearance. However, Doppler sonographic examinations revealed that the DA-HUS patients demonstrated less of a decrease in renovascular resistance with age than did the control group (p < 0.0002). After recovery, patients treated exclusively with conservative management during an acute episode of DA-HUS appeared to have an excellent long-term prognosis. Comparison of our results with those from other studies in which investigational therapies have been used during the acute phase of DA-HUS suggests that latent toxicities which cause long term sequelae may not have been appreciated previously. The clinical significance of the altered renal vascular resistance remains to be delineated.

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease.

OBJECTIVE: We assessed the current role of bilateral adrenalectomy in the overall management strategy of hypercortisolism. DESIGN: Retrospective review of case notes. PATIENTS: Twenty-six patients (20F/6M); mean age 46 years (range 15-70 years), median duration of follow-up 5.25 years (0.6-19.1 years) who had undergone bilateral adrenalectomy at the Royal Victoria Hospital since 1972. Eighteen had had prior transsphenoidal surgery which did not control the hypercortisolism. MEASUREMENTS: Morbidity, mortality, incidence of Nelson's syndrome. RESULTS: Surgery was performed through bilateral postero-lateral incisions (20 patients) or a long epigastric incision (six patients). The mean combined weight of the adrenals at surgery was 11.2 g. Twenty patients received subcutaneous heparin and 18 antibiotic prophylaxis peri and post-operatively. There was no operative mortality. Minor complications included one post-operative wound infection and a small pneumothorax requiring drainage. Major complications occurred in two other patients, both with pre-existing invasive pituitary tumours and considered at high risk because of age and general debility. One patient had a massive pulmonary embolus and the other a subphrenic abscess post-operatively. This latter patient, the only mortality, died from an unrelated cause three years post-operatively. Six patients have subsequently undergone pituitary surgery and three have received external pituitary irradiation therapy for expanding tumours. CONCLUSIONS: Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.

The influence of intensive hyperbaric oxygen therapy on skin flap survival in a swine model.

Conflicting reports exist regarding the influence of hyperbaric oxygen therapy on random skin flap survival. The present investigation sought to demonstrate enhanced survival of experimental random skin flaps in swine using an intensive and tapering hyperbaric oxygen therapy regimen that would have direct application in human clinical trials. Random cutaneous flaps were surgically constructed on 12 domestic pigs. Flaps were designed to obtain a predictable length of necrosis. Six pigs did not undergo hyperbaric oxygen therapy and served as surgical controls. Six pigs were subjected to an intensive tapering hyperbaric regimen within 1.5 hours of completing the surgical procedure. Treatments were administered in a research hyperbaric vessel at a depth of 2.0 atm absolute (10 m of seawater) for 90 minutes of oxygen treatment in a tapering schedule over 6 days. This was structured to provide intensive therapy initially during the period of maximum tissue trauma and ischemia. Extent of flap necrosis was assessed by tracing clear plastic templates at necropsy, then converting to square centimeters using a computer digitizer tablet. The difference in flap necrosis between groups was significant, with random flaps subjected to hyperbaric oxygen therapy demonstrating a mean 35% less necrosis than surgical controls. Skin flaps treated with hyperbaric oxygen therapy demonstrated a mean survival of 77%, with a range of 56% to 100%. This reflected a 12% improvement in mean surviving area for hyperbaric oxygen therapy flaps over untreated surgical controls. We are unaware of similar studies reporting a comparable degree of enhancement in random skin flap survival using hyperbaric oxygen therapy alone. Adjunctive hyperbaric oxygen therapy in an intensive tapering schedule significantly improved flap survival in this model. Further investigations need to determine the optimum frequency of treatments and depth necessary to attain maximum tissue viability.

Curettage of nontuberculous mycobacterial cervical lymphadenitis.

Cervicofacial nontuberculous mycobacterial infections of the head and neck are difficult to treat surgically because of their common location near the branches of the facial nerve. Curettage of these lesions through a small skin incision makes treatment simple without injury to the facial nerve fibers and leaves the patient with an excellent cosmetic result. Most discussions on the topic, however, favor complete surgical excision even though curettage has been reported as a safe and excellent means of treatment. For the past 2 years, the department of otolaryngology-head and neck surgery at the Geisinger Medical Center, Danville, Pa, has used curettage in seven patients as the primary treatment modality for these facial and cervical infections. A review of these cases is presented.

Changing patterns in presentation and management of the Zollinger-Ellison syndrome in Northern Ireland, 1970-1988.

The clinical features, diagnostic methods, management and survival in 16 cases of Zollinger-Ellison syndrome encountered in Northern Ireland between the years 1970 and 1988 are described. While the majority of patients in the first decade of the study period had surgical treatment, those presenting in the latter period have been managed with medical therapy in the form of H2-receptor antagonists or omeprazole. The increasing use of these agents seems to be altering the severe clinical features of this condition, reducing the indications for surgery and maintaining patients, with or without evidence of metastatic disease, in clinical remission.

Radiotherapy. The mainstay in the treatment of early glottic carcinoma.

Early squamous cell carcinoma of the glottis may be effectively treated with surgery or radiation therapy. Controversy exists as to whether radiation therapy effects survival at the expense of vocal function by ultimately requiring more total laryngectomies for salvage of local tumor recurrence. This study reviewed the medical records of 185 patients with T1 or T2, NO invasive squamous cell carcinoma of the glottis treated with primary radiation therapy between 1969 and 1984. All patients were followed up for a minimum of 5 years after completion of therapy. One hundred sixty-one patients met the criteria for local control analysis. Radiation therapy controlled disease in 93% (105 of 113) of patients with T1 lesions and 73% (38 of 48) of those with T2 tumors. Ultimate control of disease for T1 and T2 lesions, including surgical salvage, was 111 (98%) of 113 and 44 (92%) of 48 patients, respectively. The rate of successful surgical salvage was 75% (T1) and 70% (T2). The T2 lesions with impaired vocal cord mobility or anterior commissure disease were identified as being at increased risk for recurrence after primary radiation therapy. Overall voice preservation was 90%. Our data demonstrate that radiation therapy effects disease-free survival rates that are comparable to those produced by surgery, without sacrificing voice. Although a small percentage of patients with selected early glottic lesions may be more effectively treated with primary conservation surgery, these data do not support a change in philosophy concerning primary treatment of early glottic cancer with radiation therapy.

Proximal gastric vagotomy: follow-up at 10-20 years.

From August 1969 to December 1989, 600 patients had elective proximal gastric vagotomy for duodenal ulceration with an operative mortality of 0.2 per cent. Of these, 372 patients had surgery over 10 years ago. Three hundred and forty-two patients survived for more than 10 years and, in a prospective study, 305 were reviewed, forming the basis of this 10-20-year follow-up report. Forty-six (15 per cent) have had recurrent ulceration; 80 per cent of these developed symptoms within 5 years and no patient has had recurrence after 13 years. Although 29 patients required reoperation for recurrent ulceration, the current patient satisfaction rate for Visick grades I and II is 92 per cent. Only two patients required reoperation because of gastric stasis. It is concluded that proximal gastric vagotomy is a safe and satisfactory first choice operation for duodenal ulceration.

Cystic hygroma-lymphangioma: a rare and still unclear entity.

Hygroma cysticum coli or cystic hygroma remains a complex entity in terms of its development and management. Most recently, cystic hygroma has been categorized as part of a larger spectrum that includes lymphangiomas. The majority of lymphangiomas occur in the head and neck as cystic hygromas with the posterior cervical region as the most common site. Since its original description, there have been many attempts at treatment modalities: surgical excision remains the treatment of choice. The literature is reviewed and 40 cases from the author's institution are presented. The purposes of this review are, first, to bring some order to the theories and development of this lesion and its various pathological presentations. Second, to approach the treatment of these difficult lesions in an objective manner and to set up guidelines for management.