Features of patients and fracture risk in hypoparathyroidism; a single center study.

PURPOSE: Patients with hypoparathyroidism (hypoPT) have low bone turnover and high bone mineral density (BMD). However, data on fracture risk are conflicting. The objectives of this study were: 1. To describe clinical/biochemical characteristics of hypoPT patients followed at a single medical center. 2. To identify postsurgical hypoPT patients and investigate their fracture rate compared with gender/age-matched post-surgical normocalcemic patients. METHODS: Retrospective analysis of patient's medical records treated at the tertiary medical center in 2010-2021 identified by computerized medical database search. RESULTS: The cohort included 133 patients (91% women, mean age 64 ± 13 years) of whom 105 (79%) had post-thyroidectomy hypoparathyroidism and the remainder had an autoimmune/idiopathic/other etiology. Mean follow-up time was 21 ± 12 and 27 ± 12 years, respectively. The control group included 142 post-thyroidectomy patients without hypoparathyroidism. Patients in the postsurgical hypoparathyroidism group were older and had higher calcium and PTH levels at diagnosis than the non-surgical hypoPT patients. Comparing the postsurgical hypoPT and postsurgical normocalcemic control patients revealed a significantly higher BMD in the hypoPT group. Yet, fracture rates were 31% in the postsurgical hypoparathyroidism group and 21% in the control group (P = 0.1) over a similar median follow-up period (17 and 18.4 years, respectively). In both groups the most common fracture site was the spine (50% and 70%, respectively; p = 0.33), mainly nonclinical morphometric fractures. Higher phosphorus blood level was associated with increased fracture risk. CONCLUSIONS: The relatively high BMD in patients with postsurgical hypoparathyroidism is not associated with lower fracture risk. Silent morphometric fractures are quite common in this group of patients.

Familial non-medullary thyroid cancer: a critical review.

BACKGROUND: Familial non-medullary thyroid carcinoma (FNMTC), mainly of papillary histotype (FPTC), is defined by the presence of the disease in two or more first-degree relatives in the absence of other known familial syndromes. With the increasing incidence of PTC in the recent years, the familial form of the disease has also become more common than previously reported and constitutes nearly 10% of all thyroid cancers. Many aspects of FNMTC are debated, concerning both clinical and genetic aspects. Several studies reported that, in comparison with sporadic PTCs, FPTCs are more aggressive at disease presentation, while other authors reported no differences in the clinical behavior of sporadic and familial PTCs. For this reason, recent guidelines do not recommend screening of family members of patients with diagnosis of differentiated thyroid cancer (DTC). FNMTC is described as a polygenic disorder associated with multiple low- to moderate-penetrance susceptibility genes and incomplete penetrance. At the moment, the genetic factors contributing to the development of FNMTC remain poorly understood, though many putative genes have been proposed in the recent years. PURPOSE: Based on current literature and our experience with FNMTC, in this review, we critically discussed the most relevant controversies, including its definition, the genetic background and some clinical aspects as screening and treatment.

Are Thyroid Hormone Values Obtained in Hospitalized Elderly Patients Reproducible? - A Cohort Study.

It is unclear whether TSH should be obtained in elderly hospitalized patients as several factors associated with hospitalization influence these levels, which may not truly represent the thyroid status of the individual. All patients≥65 years old hospitalized in a geriatric ward in the years 2012-2014 had TSH measured irrespective of the cause for hospitalization. All patients in whom TSH levels were performed in an ambulatory setting 2-12 months following hospitalization were identified and these TSH levels were correlated with levels recorded during hospitalization. Factors influencing TSH reproducibility were identified through review of patients' medical records. Of 562 patients hospitalized during the study period, 198 had repeat ambulatory TSH measurements during follow-up. The Katz Index of Independence was higher (9.43±2.98 vs. 8.43±3.67 p=0.002) and cerebrovascular disease was less prevalent (15.6 vs. 25.2% p=0.014) in those who had a repeat TSH measurement compared with those who did not, but other baseline characteristics and TSH levels on admission were similar. Ambulatory TSH values were significantly correlated with those obtained during hospitalization (correlation coefficient=0.677), irrespective of baseline systolic blood pressure, cause of hospitalization, or admission albumin levels. Mean TSH difference between in-hospital and ambulatory was 0.65±2.36 mIU/l and in more than 94% of cases TSH values differed by less than 2 mIU/l between the 2 measurements. In hospitalized patients≥65 years old, TSH levels are highly concordant with ambulatory values. TSH obtained during hospitalization may be used for making treatment decisions and has clinical utility in this population.

Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists.

OBJECTIVE: Clinically nonfunctioning pituitary adenoma (NFPA) remains the only pituitary tumor subtype for which no effective medical therapy is available or recommended. We evaluated dopamine agonist (DA) therapy for preventing growth of postsurgical pituitary tumor remnants. DESIGN: The study design included historical cohort analysis of clinical results at two pituitary referral centers with different standard practices for postoperative NFPA management: DA therapy or conservative follow-up. METHODS: Seventy-nine patients followed for 8.8±6.5 years were treated with DA, initiated upon residual tumor detection on postoperative MRI (preventive treatment (PT) group, n=55), or when tumor growth was subsequently detected during follow-up (remedial treatment (RT) group, n=24). The control group (n=60) received no medication. Tumoral dopamine and estrogen receptor expression assessed by quantitative RT-PCR and immunostaining were correlated with response to treatment. RESULTS: Tumor mass decreased, remained stable, or enlarged, respectively, in 38, 49, and 13% of patients in the PT group, and in 0, 53, and 47% of control subjects; shrinkage or stabilization was achieved in 58% of enlarging tumors in the RT group, P < 0.0001.Fifteen-year progression-free survival rate was 0.805, 0.24, and 0.04, respectively, for PT, RT, and control groups (P<0.001). About 42% of patients in the control group required additional surgery or radiotherapy, compared with 38 and 13% subjects in the RT and PT groups, respectively (P=0.002). Outcome measures were not related to NFPA D2R abundance. CONCLUSIONS: Dopamine agonist therapy in patients with NFPA is associated with decreased prevalence of residual tumor enlargement after transsphenoidal surgical resection.

Thyroid surgery in the elderly.

BACKGROUND: The increase in life expectancy combined with the relatively high incidence of thyroid disease requiring surgery in the elderly has raised questions concerning the appropriate management of the older patient. AIM: Evaluation of the surgical management and outcome of thyroid disease requiring surgery in elderly patients. METHODS: We performed a retrospective cohort study, in which the medical charts of 2,239 patients who underwent total thyroidectomy or hemithyroidectomy between 1995 and 2011 in a tertiary medical center were reviewed for clinical, disease-related, operative and outcome measures. Findings were analyzed between the patients aged more than 75 years for whom complete information was available (n = 255) and a control group of 100 patients aged 40-60 years matched for sex and extent of surgery. RESULTS: The prevalence of comorbidities was significantly higher in the elderly. Presenting symptoms were similar in the two groups; in approximately 25% of both groups thyroid cancer was an incidental finding. There were no between-group differences in surgery duration, time to anesthesia induction, recovery time from anesthesia, or rate of postoperative complications. Hospitalization was 3 days longer on average in the older group. Malignancy rates and distribution of histologic subtypes were similar in the two groups, although the older group presented with significantly higher rates of advanced disease stage and larger tumors. There were no differences in recurrence rate both locoregional and distant metastases. However, a higher proportion of older patients failed to achieve cure. CONCLUSION: Although older patients with thyroid disease have more comorbidities and advanced disease, there is no practical difference in their operative management and surgical outcome compared to younger patients. Surgery should not be deferred solely on the basis of age in the presence of compelling indications; rather, the decision should be based on individual risk-benefit analysis.

Suspicious cervical lymph nodes detected after thyroidectomy for papillary thyroid cancer usually remain stable over years in properly selected patients.

CONTEXT: The risk of loco-regional recurrence in papillary thyroid cancer (PTC) patients ranges from 15-30%. However, the clinical significance of small-volume loco-regional recurrence detected by highly sensitive ultrasonography is unclear. OBJECTIVE: Our objective was to describe the natural history of abnormal cervical lymph nodes (LN) diagnosed after initial treatment. DESIGN: We conducted a retrospective cohort study. PATIENTS: 166 PTC with patients who had at least one abnormal LN outside the thyroid be on ultrasound and selected for active surveillance were included. MAIN OUTCOME MEASURE: LN growth during a period of active surveillance was the primary outcome. RESULTS: Most patients had classical PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the start of the observation period was 1.3 cm (range, 0.5-2.7 cm) in largest diameter, with all nodes having at least one abnormal sonographic characteristic (70% of patients had LN with at least two abnormal features). In almost all patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4 (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3 mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the clinical or sonographic features were predictive of LN growth (positive predictive value range = 0.21-0.57). There were no local complications (nerve damage or local invasion) related to the abnormal nodes and no disease-related mortality. CONCLUSIONS: Suspicious cervical LN in the lateral neck usually remain stable for long periods of time in properly selected PTC patients and can be safely followed with serial ultrasounds.

Role of Recombinant Human Thyrotropin (rhTSH) in the Treatment of Well-Differentiated Thyroid Cancer.

Since the introduction of radioiodine (RAI) for treatment of well-differentiated thyroid cancer (DTC) more than 50 years ago, prolonged periods of hypothyroidism were routinely used as part of the treatment regimen. Recombinant human TSH (rhTSH) was introduced in the 1990s as a tool to elevate the serum TSH without the need for thyroid hormone withdrawal and symptomatic hypothyroidism. After being initially approved as a diagnostic tool for use in RAI scanning and stimulated thyroglobulin testing, rhTSH was approved as an adjunct to RAI remnant ablation in patients without distant metastases in Europe in 2005 and in the US in 2007. Following successful use of rhTSH for diagnostic purposes, it has been extensively studied for use with therapeutic doses of RAI in the setting of RAI remnant ablation and is now an integral part of DCT therapy. The use of rhTSH in clinical practice in the last decade was coupled with the growing interest in an individualized, risk-stratified approach to the management of patients with DCT. While traditional treatment for DTC included surgery and RAI therapy for all patients, many more recent studies demonstrated the value of selective use of RAI only in patients who will probably benefit from treatment. This manuscript reviews the evolving role of rhTSH in the current risk adapted climate of thyroid cancer management with particular emphasis on the use of rhTSH as an aid to RAI therapy.

Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults.

BACKGROUND: Community acquired pneumonia (CAP) is caused by various pathogens, traditionally divided to 'typical' and 'atypical'. Initial antibiotic treatment of CAP is usually empirical, customarily covering both typical and atypical pathogens. To date, no sufficient evidence exists to support this broad coverage, while limiting coverage is bound to reduce toxicity, resistance and expense. OBJECTIVES: To assess the efficacy and need of adding antibiotic coverage for atypical pathogens in hospitalized patients with CAP, in terms of mortality and successful treatment. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 1) which includes the Acute Respiratory Infection Group's specialized register; MEDLINE (January 1966 to March 2007); and EMBASE (January 1980 to January 2007). SELECTION CRITERIA: Randomized trials of adult patients hospitalized due to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a regimen without atypical antibiotic coverage. DATA COLLECTION AND ANALYSIS: Two review authors independently appraised the quality of each trial and extracted the data from included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated, assuming an intention-to-treat (ITT) basis for the outcome measures. MAIN RESULTS: Twenty five trials were included, encompassing 5244 randomized patients. There was no difference in mortality between the atypical arm and the non-atypical arm (RR 1.15; 95% CI 0.85 to 1.56). The atypical arm showed an insignificant trend toward clinical success and a significant advantage to bacteriological eradication, which disappeared when evaluating methodologically high-quality studies alone. Clinical success for the atypical arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and non-significantly lower for pneumococcal pneumonia. There was no significant difference between the groups in the frequency of (total) adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). All but two included trials compared a single atypical antibiotic to a beta-lactam, while no trials assessing the addition of an atypical antibiotic to a beta-lactam were identified. AUTHORS' CONCLUSIONS: No benefit of survival or clinical efficacy was shown to empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams (BL) or cephalosporins. Further trials, comparing BL or cephalosporins therapy to BL or cephalosporins combined with a macrolide in this population, using mortality as its primary outcome, should be performed.

The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes.

Risk factors and outcomes for patients with nosocomial Acinetobacter baumannii bacteraemia were compared with those for patients with nosocomial Klebsiella pneumoniae bacteraemia in a single centre in Israel between 2000 and 2003. Data were collected retrospectively through patient chart review. In total, 112 patients with A. baumannii bacteraemia and 90 patients with K. pneumoniae bacteraemia were identified. A. baumannii was significantly associated with poorer performance status, mechanical ventilation, presence of devices, prior treatment with carbapenems, pneumonia as the source of infection and inappropriate empirical antibiotic treatment. All-cause 30-day mortality was higher for A. baumannii bacteraemia compared with K. pneumoniae bacteraemia (61.6% vs 38.9%, P=0.001). Variables significantly associated with mortality at the univariate level (P<0.1) were entered into a multi-variable logistic regression model for mortality. A. baumannii remained significantly associated with mortality when adjusted for all other risk factors (odds ratio 3.61, 95% confidence interval 1.55-8.39). This result did not change when the analysis was repeated for subgroups of less severely ill patients, i.e. those who were not ventilated and those who did not present with septic shock. These results support the view that nosocomial bacteraemia due to A. baumannii is associated with increased mortality.

[West Nile fever: the virus, the mosquito, the disease and our coping].

West Nile fever is a viral disease, transmitted to humans by a mosquito bite. An outbreak of West Nile fever occurred last year in Israel, causing substantial morbidity and mortality. This article reviews the literature regarding this disease, focusing on several recent outbreaks around the world, and with special emphasis on the situation here, in Israel. Recommendations for better coping with future outbreaks to the general public, health authorities and state leaders, are presented at the end of the article.

Antibiotic use in patients with erysipelas: a retrospective study.

BACKGROUND: Erysipelas is a skin infection generally caused by group A streptococci. Although penicillin is the drug of choice, some physicians tend to treat erysipelas with antibiotics other than penicillin. OBJECTIVES: To define the pattern of antibiotic use, factors affecting antibiotic selection, and outcome of patients treated with penicillin versus those treated with other antimicrobial agents. METHODS: A retrospective review of charts of adult patients with discharge diagnosis of erysipelas was conducted for the years 1993-1996. RESULTS: The study group comprised 365 patients (median age 67 years). In 76% of the cases infection involved the leg/s. Predisposing condition/s were present in 82% of cases. Microorganisms were isolated from blood cultures in only 6 of 176 cases (3%), and Streptococcus spp. was recovered in four of these six patients. Cultures from skin specimens were positive in 3 of 23 cases. Penicillin alone was given to 164 patients (45%). Other antibiotics were more commonly used in the second half of the study period (P < 0.0001) in patients with underlying conditions (P = 0.06) and in those hospitalized in the dermatology ward (P < 0.0001). Hospitalization was significantly shorter in the penicillin group (P = 0.004). There were no in-hospital deaths. CONCLUSIONS: We found no advantage in using antibiotics other than penicillin for treating erysipelas. The low yield of skin and blood cultures and their marginal impact on management, as well as the excellent outcome suggest that this infection can probably be treated empirically on an outpatient basis.

Evaluation of chlorhexidine and povidone iodine activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis using a surface test.

Most published studies of the activity of biocides against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) have been based on suspension tests. This study was undertaken to provide information on the effect of chlorhexidine and povidone iodine on bacteria dried on to surfaces, a situation in which biocide activity is known to be reduced. The inactivation of MRSA (10 strains), methicillin-sensitive Staphylococcus aureus (MSSA, 10 strains), VRE (nine strains) and vancomycin-sensitive Enterococcus faecalis (VSE, 10 strains) by 0.5% aqueous chlorhexidine gluconate or 10% povidone iodine was evaluated by applying the European surface test method. Povidone iodine was equally active against resistant and sensitive strains of both species with microbicidal effects (ME), i.e. the log(10)concentration of micro-organisms compared with controls treated with distilled water, after 1.5 min of 3.14 and 3.49 for VRE and VSE respectively, and 3.47 and 3.78 for MRSA and MSSA. Chlorhexidine was equally active against VRE and VSE (ME 3.37 vs. 3. 56 after 7 min, respectively), but was significantly less active against MRSA as opposed to MSSA (ME 3.07 vs. 3.83 after 10 min, P= 0. 017).

Prosthetic knee septic arthritis due to Pseudomonas stutzeri.

Prosthetic joint infection is usually caused by Staphylococcus aureus, coagulase-negative staphylococci and, less commonly, by Gram-negative bacilli and anaerobes. A case of prosthetic joint infection due to Pseudomonas stutzeri in a 73-year-old female with acute promyelocytic leukemia is presented, and the pertinent literature is reviewed. Although the patient had prolonged neutropenia, the infection was successfully treated with antibiotics and without artificial joint replacement.

Infective endocarditis in renal transplant recipients.

Because of the increasing number of renal transplantations performed and the rarity of reported cases of infective endocarditis in these patients, we studied the clinical characteristics of this infection in this population. We report on two cases from our experience and review reported cases of infective endocarditis in renal transplant recipients retrieved from the MEDLINE system. In addition, we reviewed a large series of infective endocarditis looking for patients with renal transplants. In addition to our 2 cases, 12 previously reported cases were found. The mean time from transplantation to diagnosis of infective endocarditis was 3.5 years (range 2 months to 15 years). Causative organisms included fungi, Staphylococcus aureus (3 cases each), Corynebacterium sp. (2 cases), Streptococcus viridans, VRE, Brucella sp., Clostridium sp., Nocardia sp. and Erysipelothrix sp. (one case each). Skin manifestations of endocarditis and/or splenomegaly were not reported in these patients. Septic emboli and mycotic aneurysms were relatively common. The overall mortality rate was 50% (7 of 14 patients died). Infective endocarditis seems to be rare in renal transplant recipients. The few reported cases are characterized by unusual causative micro-organisms and atypical clinical presentation. Further studies are needed to delineate the magnitude and scope of this association.