Immunogenicity and SARS-CoV-2 Infection following the Fourth BNT162b2 Booster Dose among Health Care Workers.

INTRODUCTION: The fourth SARS-CoV-2 vaccine dose was found to protect against infection and more importantly against severe disease and death. It was also shown that the risk of symptomatic or severe disease was related to the antibody levels after vaccination or infection, with lower protection against the BA.4 BA.5 Omicron variants. The aim of our study was to assess the impact of the fourth dose on infection and perception of illness seriousness among healthcare workers (HCWs) at a tertiary health care campus in Haifa, Israel, and to investigate the possible protective effect of antibody levels against infection. METHODS: We conducted a prospective cohort study among fully vaccinated HCWs and retired employees at Rambam Healthcare Campus (RHCC), a tertiary hospital in northern Israel. Participants underwent serial serological tests at 1, 3, 6, 9, 12 and 18 months following the second BNT162b2 vaccine dose. Only a part of the participants chose to receive the fourth vaccine. A multivariable logistic regression was conducted to test the adjusted association between vaccination, and the risk of infection with SARS-CoV-2. Kaplan-Meier SARS-CoV-2 free "survival" analysis was conducted to compare the waning effect of the first and second, third and fourth vaccines. Receiver Operating Characteristic (ROC) curve was plotted for different values of the sixth serology to identify workers at risk for disease. RESULTS: Disease occurrence was more frequent among females, people age 40-50 years old and those with background chronic lung disease. The fourth vaccine was found to have better protection against infection, compared to the third vaccine; however, it also had a faster waning immunity compared to the third vaccine dose. Antibody titer of 955 AU/mL was found as a cutoff protecting from infection. CONCLUSIONS: We found that the fourth vaccine dose had a protective effect, but shorter than the third vaccine dose. Cutoff point of 955 AU/mL was recognized for protection from illness. The decision to vaccinate the population with a booster dose should consider other factors, including the spread of disease at the point, chronic comorbidities and age, especially during shortage of vaccine supply.

Third BNT162b2 Vaccine Booster Dose against SARS-CoV-2-Induced Antibody Response among Healthcare Workers.

This study assessed humoral response to the third BNT162b2 dose among healthcare workers (HCW). This prospective cohort study of HCW tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) at 1, 3, 6, 9, and 12 months after receiving the second BNT162b2 vaccine dose (tests 1, 2, 3, 4, and 5, respectively). A third (booster) vaccination dose was introduced before test 4. Linear regression model was used to determine the humoral response following vaccine doses. For each serology test, changes in log-transformed antibody concentrations over time, adjusted for age, sex, underlying diseases, steroid treatment, and smoking were described using the general linear mix model. Serology tests were performed at 3, 6, 9, and 12 months after the second vaccine dose in 1113, 1058, 986, and 939 participants, respectively. The third dose was received by 964 participants before the 9-month tests, 797 of whom participated in the 9- and 12-month serology tests. A significant inverse correlation was noted between time from third dose and antibody concentrations (Spearman correlation −0.395; p < 0.001). Age (p < 0.0001; CI 95% −0.005−−0.004), heart disease (p < 0.0001; CI 95% −0.177−−0.052), immunodeficiency (p < 0.0001; CI 95% 0.251−−0.106), and smoking (p < 0.0001; CI 95% −0.122−−0.040) were significantly associated with decreased antibody concentrations. Female sex (p = 0.03; CI 95% 0.013−0.066) was associated with increased antibody concentrations. The third booster dose had a better effect on immunogenicity, with higher antibody concentrations among tested HCW. Heart disease, smoking, and other known risk factors were associated with decreased antibody concentrations.

Association between IgG antibody levels and adverse events after first and second Bnt162b2 mRNA vaccine doses.

OBJECTIVES: This study sought to correlate the SARS-CoV-2 IgG antibody response level to the BNT162b2 (Pfizer BioNTech) mRNA vaccine after the first and second doses with the reported adverse events. METHODS: This cohort study examined the adverse events profiles of people vaccinated with BNT162b2 in our institute between late 2020 and May 2021. Adverse events, age, and sex were reported using an electronic questionnaire, and their SARS-CoV-2 IgG antibody levels were retrieved from the hospital database. RESULTS: Between 20 December 2020 and 31 May 2021, the adverse events questionnaire was completed by 9700 individuals who received the first vaccine dose and 8321 who received the second dose. After the first and second doses, the average antibody levels were 62.34 AU/mL (mean 4-373) and 188.19 AU/mL (mean 20-392), respectively. All of the adverse events, except local pain, were more common after the second vaccine dose. Multivariate analysis showed that after the first vaccine dose, female sex and younger age (but not IgG titres) were associated with a higher probability of adverse events (OR 2.377, 95% CI, 1.607-3.515, p = 0.000; OR 0.959, 95% CI, 0.944-0.977, p £0.000; OR 1.002, 95% CI, 0.995-1.008, p £0.601; respectively); however, all three parameters were associated with the incidence of adverse events after the second dose (OR 2.332, 95% CI, 1.636-3.322, p = 0.000; OR 0.984, 95% CI, 0.970-0.999, p £0.039; OR 1.004, 95% CI, 1.001-1.007, p £0.022; respectively). DISCUSSION: Adverse events are significantly more common after the second BNT162b2 vaccine dose than after the first dose. We found an association between sex, age, and SARS-CoV-2 IgG antibody titre with the incidence of adverse events.

COVID-19: Healthcare Workers May Be at Greater Risk Outside Their Work Environment-A Retrospective Observational Study.

BACKGROUND: With the availability of coronavirus disease 2019 (COVID-19) vaccine, concerns have been raised regarding pre-vaccination seroprevalence in healthcare workers (HCW). This study examines the seroprevalence of HCW at an Israeli tertiary medical center before first BNT162b2 vaccination. METHODS: This was a retrospective observational study. Before vaccination, HCW at our center were offered serological testing. Data on their epidemiological, workplace, and quarantine history were collected. The SARS-CoV-2 IgG assay was performed pre-vaccination. RESULTS: A total of 4,519 (82.5%) of the HCW were tested. Of these, 210 were seropositive; 101 had no known history of COVID-19. Of the 101 asymptomatic HCW, only 3 (3%) had worked at COVID-19 departments, and 70 (69.3%) had not been previously quarantined. Positive serology was similarly distributed across age groups, and about 40% had no children. Nearly half of the HCW tested were administrative and service staff. Overall, seropositive tests were associated with having no children (OR 1.42, 95% CI 1.06-1.89; P=0.0218), history of having been quarantined without proof of disease (OR 6.04, 95% CI 4.55-8.01; P<0.001), and Arab ethnicity (OR 3.36, 95% CI 2.54-4.43; P<0.001). Seropositivity was also more prevalent in members of the administration compared to other sectors, medical and paramedical, who are exposed to patients in their daily work (OR 1.365, 95% CI 1.02-1.82; P=0.04). CONCLUSIONS: The low percentage of asymptomatic COVID-19 among our HCW may reflect the high compliance to personal protective equipment use despite treating hundreds of COVID-19 patients. The relatively high number of childless seropositive HCW could reflect misconceptions regarding children as a main source of infection, leading to carelessness regarding the need for appropriate out-of-hospital protection.

Minimally Invasive Parathyroidectomy: Can Intraoperative Parathyroid Hormone Monitoring be Omitted?

BACKGROUND: Intraoperative PTH (ioPTH) monitoring has become widely accepted in the era of minimally invasive parathyroidectomy (MIP). The purpose of this study was to evaluate the need for ioPTH during parathyroidectomy in patients with positive preoperative imaging. METHODS: The charts of patients who underwent parathyroidectomy at three tertiary centers between the years 2012 and 2021 were retrospectively reviewed. Patients were defined as MIP candidates with either concordant preoperative imaging or a single positive imaging. Patients with negative or discordant imaging, concomitant thyroidectomy, or previous neck surgery were excluded. RESULTS: Of a total of 1013 patients who underwent parathyroidectomy, 535 (52.8%) were defined as MIP candidates and were included in the statistical analysis. Surgical success was achieved in all patients. A single adenoma that corresponded to the preoperative imaging was identified and resected in 517 (93.8%) patients. In only 18 (3.3%) patients, the ioPTH correctly changed the operative management where additional pathologic glands were identified and excised. Patients with additional lesions were significantly more likely to have decreased index adenoma size as indicated either by preoperative imaging or by intraoperative findings (15.5 ± 6.6 vs. 8.3 ± 2.5 mm, p < 0.001). None of the patients with an adenoma size greater than 13 mm had an additional pathologic gland. CONCLUSIONS: Our findings suggest that the routine use of ioPTH in MIP candidates may be omitted in patients with an index adenoma greater than 13 mm, even with only a single positive preoperative imaging study, without compromising surgical success.

Gastric and urinary bladder pressures correlate with intra-abdominal pressure in patients with morbid obesity.

Intra-abdominal pressure (IAP) affects cardio-respiratory and hemodynamic parameters and can be measured directly or indirectly by measuring gastric or urinary bladder pressure. The aim of this study was to investigate the correlation between IAP, gastric pressure and urinary bladder pressure in patients with morbid obesity, at normal and elevated levels of IAP in two positions. As well, to examine the effects of increasing IAP and patient's position on hemodynamic and respiratory parameters. Twelve patients undergoing laparoscopic bariatric surgery were included. IAP, gastric pressure, and urinary bladder pressure were measured while patients were in the supine position and after 45° anti-Trendelenburg tilt. Mean inspiratory pressure, peak inspiratory pressure, and tidal volume were recorded and assessed. In supine position; directly measured IAP was 9.1 ± 1.8 mmHg, compared to 10 ± 3.6 and 8.9 ± 2.9 mmHg in the stomach and bladder, respectively. Increasing IAP to 15 mmHg resulted in an increased gastric pressure of 17 ± 3.8 mmHg, and urinary bladder pressure of 14.8 ± 3.9 mmHg. Gastric and urinary bladder pressures strongly correlated with IAP (R = 0.875 and 0.847, respectively). With 45° anti-Trendelenburg tilt; directly measured IAP was 9.4 ± 2.2 mmHg, and pressures of 10.8 ± 3.8 mmHg and 9.2 ± 3.8 mmHg were measured in the stomach and the bladder, respectively. Increasing IAP to 15 mmHg resulted in elevating gastric and bladder pressures to 16.6 ± 5.3 and 13.3 ± 4 mmHg, respectively. Gastric and urinary bladder pressures had good correlation with IAP (R = 0.843 and 0.819, respectively). Changing patient position from supine to 45° anti-Trendelenburg position resulted in decreased mean and peak inspiratory pressures, and increased tidal volume. Basal IAP is high in patients with morbid obesity. IAP shows positive correlation to gastric and urinary bladder pressures at both normal and elevated levels of IAP. Anti-Trendelenburg tilt of mechanically ventilated morbidly obese patients resulted in favorable effects on respiratory parameters.Trial Registration: The study was retrospectively registered in the NIH registry. Registration number is pending.

Immunogenicity trends 1 and 3 months after second BNT162B2 vaccination among healthcare workers in Israel.

OBJECTIVES: We evaluated the antibody response to the BNT162B2 vaccine among healthcare workers (HCWs) to identify factors associated with decreased immunogenicity. METHODS: This prospective cohort study included consenting HCWs who completed a questionnaire regarding background illnesses, medications, and post-vaccination allergic reactions or rash. All HCWs were tested for anti-spike antibodies (LIAISON SARS-CoV-2 S1/S2 IgG assay) 1 and 3 months after the second vaccine dose. A multivariate mixed linear model was adjusted to participants' data and fit to predict antibody levels after the second BNT162B2 vaccine dose, based on antibody levels at 1 month and the slope between 3 months and 1 month. Multivariate analyses identified factors associated with lower antibody levels. RESULTS: In total 1506 HCWs were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Older age was associated with lower mean antibody levels (-1.22 AU/mL, p < 0.001, 95%CI -1.43 to -1.01). In addition, male sex (-22.16 AU/mL, p < 0.001, 95%CI -27.93 to -16.39), underlying condition (-10.86 AU/mL, p 0.007, 95%CI -18.81 to -2.91) and immunosuppressive treatment (-28.57 AU/mL, p 0.002, 95%CI -46.85 to -10.29) were associated with significantly lower mean antibody levels. Allergic reactions after vaccine administration or peri-vaccination glucocorticosteroid treatment were not correlated with antibody levels. CONCLUSIONS: Most HCWs had measurable antibodies at 3 months. Risk factors for lower antibody levels were older age, male sex, underlying condition, and immunosuppressive treatment. These factors may be considered when planning booster doses during vaccine shortages.

Single BNT162b2 vaccine dose produces seroconversion in under 60 s cohort.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has led to worldwide vaccination development efforts. In December 2020 the Pfizer BNT162b2 vaccine was approved in the United States. This study describes the first BNT162b2 vaccine dose effect on a large cohort. METHODS: This retrospective study examined first vaccine dose effect on serology and investigated the associations between seroconversion and age or sex. RESULTS: Serological blood tests were performed on 1898 participants following first vaccine dose; 81% were tested on day 21, before receiving the second dose (mean age 47.5 ± 12.45; median 47.7, range 18-90). Positive serology was found in 92.7% of day 21 tests. Overall positivity was 86.8%, with rates increasing from 2.5% within 1-14 days to 89.8% (14-20 days), 92.7% (21 days), and 95.9% (>21 days). Mean antibody levels 21 days after first dose were 64.3 ± 33.01 AU/ml, (range 15-373 AU/ml, median 61 AU/ml). Seropositivity was greater in females than males (88.3%. vs 83.3% respectively, p < 0.001; OR1.515; 95% CI 1.152-1.994). Older age > 60 years was associated with decreased likelihood of seropositivity (p < 0.001; OR 0.926; 95% CI 0.911-0.940). Longer time between first vaccination and serology tests was associated with increased likelihood for seropositivity (p < 0.001; OR 1.350; 95% CI 1.298-1.404). CONCLUSIONS: The high seroconversion rate following first BNT162b2 dose among individuals < 60 may justify delayed delivery of the second dose, potentially help relieve the worldwide vaccination supply shortage, enable vaccination of twice this population within a shorter period, and ultimately reduce COVID-19 contagion.

Validation of TIRADS ACR Risk Assessment of Thyroid Nodules in Comparison to the ATA Guidelines.

OBJECTIVES: The prevalence of thyroid nodules in adults, detected by ultrasound (US), is reported as high as 68%. US-guided fine-needle aspiration biopsy (FNAB) is the test of choice used to determine the nature of the nodules. However, not more than 15% are found to be malignant. Reducing the number of unnecessary FNAB while identifying clinically significant malignant nodules is imperative. There are several guidelines suggested for risk stratification of thyroid nodules by US. The aim of our study was to validate and compare Thyroid Imaging Reporting and Data System (TIRADS) American College of Radiology (ACR) and American Thyroid Association (ATA) risk stratification, specifically pertaining to reduction of unnecessary biopsies. MATERIAL AND METHODS: The study included 281 nodules in 245 patients who underwent FNAB between May 2018 and June 2019. Statistical analysis was performed only on 235 nodules that according to the TIRADS ACR and/ or ATA guidelines were eligible for FNAB. Data collected included nodule characteristics with corresponding TIRADS and ATA grading and cytological results using Bethesda scoring. RESULTS: An agreement was found between the two criteria methods in 58.2% (137/235) of the cases. In 35.3% (83/235), ATA recommended FNAB while TIRADS did not. The specificity for ATA criteria was 7% (15/221) and for TIRADS was 37% (81/221). The sensitivity was 100% (14/14) for ATA and 86% (12/14) for TIRADS. CONCLUSION: Application of ACR TIRADS criteria can reduce the number of US-guided FNAB performed on benign nodules compared to ATA criteria, by 35%, with a cost of only two missed carcinomas that remained on further follow-up.

Teaching During the COVID-19 Pandemic: The Experience of the Faculty of Medicine at the Technion-Israel Institute of Technology.

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic forced drastic changes in all layers of life. Social distancing and lockdown drove the educational system to uncharted territories at an accelerated pace, leaving educators little time to adjust. OBJECTIVES: To describe changes in teaching during the first phase of the COVID-19 pandemic. METHODS: We described the steps implemented at the Technion-Israel Institute of Technology Faculty of Medicine during the initial 4 months of the COVID-19 pandemic to preserve teaching and the academic ecosystem. RESULTS: Several established methodologies, such as the flipped classroom and active learning, demonstrated effectiveness. In addition, we used creative methods to teach clinical medicine during the ban on bedside teaching and modified community engagement activities to meet COVID-19 induced community needs. CONCLUSIONS: The challenges and the lessons learned from teaching during the COVID-19 pandemic prompted us to adjust our teaching methods and curriculum using multiple online teaching methods and promoting self-learning. It also provided invaluable insights on our pedagogy and the teaching of medicine in the future with emphasis on students and faculty being part of the changes and adjustments in curriculum and teaching methods. However, personal interactions are essential to medical school education, as are laboratories, group simulations, and bedside teaching.

Hospital solution for COVID-19 isolation facility.

OBJECTIVE: In response to the coronavirus disease 2019 (COVID-19) pandemic, the Israeli government strategy initially focused on containment. The Ministry of Health mandated isolation of COVID-19 patients in hospitals and instructed healthcare institutions to make necessary arrangements. As the second Israeli hospital to establish a COVID-19 department, this article describes our experience in its rapid establishment, while maintaining normal medical center activities. SETTING: Establishing the COVID-19 department involved planning, set-up, and implementations phases, each one based on knowledge available regarding the pandemic and established medical standards for isolation and protection of patients and staff. Wherever possible, new innovative technologies were utilized to provide maximum protection for both patients and staff, together with special online training that was developed for medical teams. RESULTS: A COVID-19 department was successfully established on the hospital campus, remote from other ongoing patient activities. A novel methodology of disease-adapted medicine was implemented successfully among the department's medical staff, who underwent training tailored to expected clinical scenarios. The COVID-19 department is receiving patients, with no contamination of medical personnel to date. A recent survey of COVID-19 patients revealed a very high patient satisfaction rate. CONCLUSION: Based on the experience described herein and lessons learned, the hospital is preparing for a potential large-scale COVID-19 wave, aimed at full readiness through utilization of a fortified underground emergency hospital to treat up to 900 COVID-19 patients, and establishment of versatile in-hospital infrastructure for quick conversion from standard conditions to COVID-19 appropriate conditions.

Israeli underground hospital conversion for treating COVID-19 patients.

OBJECTIVE: This paper describes how a large academic medical center solved the challenges of war preparedness and subsequently adapted them for the COVID-19 pandemic. SETTING: A 1,000-bed academic medical center in Northern Israel has faced two extreme challenges since 2006: operating under missile attack during the 2006 Second Lebanon War, and rapid establishment of a scalable infrastructure for COVID-19 patients. The first challenge led to construction of a dual-use facility: a parking lot during peacetime, and a fully functioning fortified underground emergency hospital (FUEH) in times of emergency. Several drills have confirmed readiness for various scenarios including conventional and unconventional warfare, and treating isolated patients during the Ebola and SARS threats. RESULTS: The hospital achieved preparedness for patient care during the COVID-19 pandemic, including all facilities and personnel, including infrastructure, laboratories, and innovations, to maintain standard patient care and separate COVID-19 treatment facilities. The hospital's second challenge represented by the COVID-19 pandemic led to adaptation of the FUEH as a key strategic facility in Northern Israel for treating hundreds of COVID-19 patients. Each solution was supported by innovations targeted for specific purposes and needs. CONCLUSIONS: The function and unique mechanisms used to leverage use of a dual facility was proven viable for several emergency conditions, including the COVID-19 pandemic. Infrastructure and technological flexibility is essential when planning for handling different emergencies situations.

Delayed discharges from a tertiary teaching hospital in Israel- incidence, implications, and solutions.

OBJECTIVES: The Israeli health system is facing high workloads with average occupancy in certain hospital wards of around 100%. Since there is a shortage of hospitalization beds in institutions for continuous, long-term care, transferring patients from the general hospitals' wards is often delayed. This situation has many significant ramifications, to the waiting patients themselves, to other patients who are waiting to be treated and to the entire organization. In this study, we describe the phenomenon of the "detained patients" - its extent, characteristics, significance, and possible solutions. MATERIALS AND METHODS: Rambam Health Care Campus is a tertiary medical center serving the population of the northern part of Israel. In recent years, the hospital management documents data regarding the "detained patients". We reviewed hospital data of detained patients over a period of nine months. The data concerning adult patients awaiting transfer to an institution for continuous care, between May 2019 and January 2020, were obtained retrospectively from the computerized database of the social service. RESULTS: During the study period, 12,723 adult patients were discharged. Of those, 857 patients (6.74%) were transferred to one of the facilities providing prolonged institutional care. For that group of patients, median inpatient waiting time from the decision to discharge until the transfer was 8 days (IQR 6-14), translating to 10,821 waiting days or 1202 hospitalization days per month. These hospitalization days account for 9.35% of the total hospitalization days during the study period. The "detained patients" were hospitalized in internal medicine wards (32%), orthopedic (30%), and neurology/neurosurgery (26%) departments. At any given moment, about 40 hospitalized patients were waiting for long-term care facilities. CONCLUSIONS: Health-care systems must adapt to the current patients' case-mix to achieve optimal utilization of hospital beds and maximal operational efficiency. The number of long-term care beds should be increased, the coordination between general hospitals, health maintenance organizations and long-term facilities improved, and patients that may require long term care after the acute phase of their illness should be early identified and addressed. Meanwhile, establishment of organic units for waiting patients and reorganization of the hospital structure should be considered.

Preoperative localization modalities in primary hyperparathyroidism: Correlation with postoperative cure.

BACKGROUND: Accurate preoperative localization is critical to the success of minimally invasive parathyroidectomy. This investigation aimed to assess the correlation among preoperative imaging results, intraoperative findings, and postoperative cure rates in patients undergoing operation for primary hyperparathyroidism. METHODS: A retrospective review of all patients who underwent operation for primary hyperparathyroidism between June 2010 and March 2016 was performed. RESULTS: During the study period, 398 patients underwent parathyroidectomy. The overall cure rate was 97.5%. The ultrasonography performed by the surgeon was superior to the ultrasonography performed by the radiologist and to the sestamibi scan in lateralizing the adenoma correctly (80% vs 62% vs 70%, P < .001, respectively), and had the greatest sensitivity (93%) and accuracy (80%) among all tests (P < .001). Age ≥65 was found to be associated with lesser cure rates (94% vs 99.2%, P = .003). The number of positive preoperative studies correlated with cure rate, ranging from 80% for patients with 0 positive studies, to 100% in those with 4 positive studies (P = .0004). In patients with a negative sestamibi and an ultrasonography performed by the radiologist, there was no significant difference in the cure rates among those with no preoperative computed tomography, a positive preoperative computed tomography, or a negative preoperative computed tomography. CONCLUSION: An ultrasonography performed by an experienced surgeon is an extremely valuable preoperative localization modality. The cure rate obtained is proportional to the number of positive imaging studies. In patients with negative ultrasonography performed by a nonexperienced radiologist and a negative sestamibi scan, the performance of computed tomography does not seem to increase cure rate. Patients with no positive preoperative scans represent a challenging subgroup, with cure rates of approximately 80%.

[SHOULD PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AND NEGATIVE IMAGING STUDIES BE REFERRED TO SURGERY?]

INTRODUCTION: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (PHPT). In cases where imaging fails to demonstrate an adenoma, a bilateral neck exploration (BNE) is performed. Negative imaging is thought to predict surgical failure, and patients with negative imaging are often not referred for surgery. These patients are at risk for disease progression. AIMS: Evaluate the effect of negative imaging on surgical findings and the cure rate in patients with PHPT. METHODS: A total of 133 patients underwent parathyroidectomy for PHPT. Data were retrospectively retrieved including preoperative imaging, surgical findings and results. A comparison was conducted between patients with negative and positive imaging. The main outcome measure was cure. RESULTS: A negative MIBI (methoxy-isobutyl-isonitrile) scan was seen in 30 (22%) patients and a negative US in 46 (34.5%). Patients with negative MIBI scan more commonly underwent BNE compared with patients with a positive scan (53% vs. 25%, respectively, p=0.0046). Patients with negative imaging had a significantly higher rate of multigland disease compared with patients with positive imaging (35% vs. 12%, p=0.004, for the MIBI scan; 27% vs. 12%, p=0.024, for the US, respectively). Overall cure rate was 96%. Highest cure rates were seen in patients with both positive MIBI and US (99% cure rate) and lowest cure rates of 67% in patients with triple negative imaging (MIBI scan, US and 4DCT (Dual computed tomography)) (p=0.003). CONCLUSIONS: Localization of an adenoma in preoperative imaging predicts very high cure rates in patients with PHPT. Negative imaging increases the risk for multigland disease and is associated with lower cure rates.

Computerized cytometry and wavelet analysis of follicular lesions for detecting malignancy: A pilot study in thyroid cytology.

BACKGROUND: The cytologic diagnosis of indeterminate lesions of the thyroid involves much uncertainty, and the final diagnosis often requires operative resection. Computerized cytomorphometry and wavelets analysis were examined to evaluate their ability to better discriminate between benign and malignant lesions based on cytology slides. METHODS: Cytologic reports from patients who underwent thyroid operation in a single, tertiary referral center were retrieved. Patients with Bethesda III and IV lesions were divided according to their final histopathology. Cytomorphometry and wavelet analysis were performed on the digitized images of the cytology slides. RESULTS: Cytology slides of 40 patients were analyzed. Seven patients had a histologic diagnosis of follicular malignancy, 13 had follicular adenomas, and 20 had a benign goiter. Computerized cytomorphometry with a combination of descriptors of nuclear size, shape, and texture was able to predict quantitatively adenoma versus malignancy within the indeterminate group with 95% accuracy. An automated wavelets analysis with a neural network algorithm reached an accuracy of 96% in identifying correctly malignant vs. benign lesions based on cytology. CONCLUSION: Computerized analysis of cytology slides seems to be more accurate in defining indeterminate thyroid lesions compared with conventional cytologic analysis, which is based on visual characteristics on cytology as well as the expertise of the cytologist. This pilot study needs to be validated with a greater number of samples. Providing a successful validation, we believe that such methods carry promise for better patient treatment.

Preoperative [99mTc]MIBI SPECT/CT Interpretation Criteria for Localization of Parathyroid Adenomas-Correlation with Surgical Findings.

PURPOSE: Minimally invasive surgery for parathyroid adenomas (PTA) requires precise identification and localization of the diseased gland prior to exploration for optimal surgical planning. The Perrier classification allows for accurate, reproducible, and reliable description of PTA location and communication of clinically significant information to surgeons. The current study compares the Perrier localization of PTA on [99mTc]methoxyisobutylisonitrile ([99mTc]MIBI) single-photon emission computed tomography (SPECT)/X-ray computed tomography (CT) with the results of surgery. PROCEDURES: Eighty-eight patients (60 females), age 13-82 years, with primary hyperparathyroidism underwent [99mTc]MIBI SPECT/CT prior to surgery. Eight patients had parathyroid hyperplasia and underwent excision of 3.5 parathyroid glands, including five patients with a negative [99mTc]MIBI study and three patients with multiple foci of uptake, and were excluded from further analysis. Each PTA was localized to Perrier levels A-G. The surgeon located each PTA found on surgery using the same classification. PTA localization on SPECT/CT and at surgery was compared. RESULTS: Eighty patients with surgically confirmed PTA were analyzed. On [99mTc]MIBI SPECT/CT, 63 patients had a single and one patient had two PTAs for a total of 65 PTAs. At surgery, 85 PTAs were resected in 80 patients, including 75 patients with single and 5 with two PTAs. Twenty PTAs found on surgery were not detected on [99mTc]MIBI. The relatively lower weight of these 20 PTAs is probably the main reason for the false-negative results group. The same Perrier localization was determined on SPECT/CT and surgery in 52/65 PTAs (80 %). In the 13 incongruent cases, the PTAs were localized at different locations but on the same side of the thyroid gland. CONCLUSIONS: [99mTc]MIBI SPECT/CT accurately localized a PTA according to the Perrier classification in 80 % of cases. Reporting SPECT/CT results using anatomy-based PTA localization criteria accepted by surgeons can contribute significantly towards better interspecialty communication and will improve performance of minimally invasive surgical removal of PTAs.

Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It?

BACKGROUND: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease. METHODS: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed. RESULTS: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%). CONCLUSIONS: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Parathyroid carcinoma.

Parathyroid carcinoma is a rare form of endocrine malignancy accounting for only a small minority of cancer cases. Due to the rarity of this cancer, there are no generalized guidelines for its management; however, surgery remains to be the mainstay therapy. The purpose of this article is to review and summarize the available literature on parathyroid carcinoma, while discussing proposed staging systems and the role of available adjuvant therapies.