Estimation of monkeypox spread in a nonendemic country considering contact tracing and self-reporting: A stochastic modeling study.

In May 2022, monkeypox started to spread in nonendemic countries. To investigate contact tracing and self-reporting of the primary case in the local community, a stochastic model is developed. An algorithm based on Gillespie's stochastic chemical kinetics is used to quantify the number of infections, contacts, and duration from the arrival of the primary case to the detection of the index case (or until there are no more local infections). Different scenarios were set considering the delay in contact tracing and behavior of infectors. We found that the self-reporting behavior of a primary case is the most significant factor affecting outbreak size and duration. Scenarios with a self-reporting primary case have an 86% reduction in infections (average: 5-7, in a population of 10 000) and contacts (average: 27-72) compared with scenarios with a non-self-reporting primary case (average number of infections and contacts: 27-72 and 197-537, respectively). Doubling the number of close contacts per day is less impactful compared with the self-reporting behavior of the primary case as it could only increase the number of infections by 45%. Our study emphasizes the importance of the prompt detection of the primary case.

A model-based strategy for the COVID-19 vaccine roll-out in the Philippines.

COVID-19 has affected millions of people worldwide, causing illness and death, and disrupting daily life while imposing a significant social and economic burden. Vaccination is an important control measure that significantly reduces mortality if properly and efficiently distributed. In this work, an age-structured model of COVID-19 transmission, incorporating an unreported infectious compartment, is developed. Three age groups are considered: young (0-19 years), adult (20-64 years), and elderly (65+ years). The transmission rate and reporting rate are determined for each group by utilizing the number of COVID-19 cases in the National Capital Region in the Philippines. Optimal control theory is employed to identify the best vaccine allocation to different age groups. Further, three different vaccination periods are considered to reflect phases of vaccination priority groups: the first, second, and third account for the inoculation of the elderly, adult and elderly, and all three age groups, respectively. This study could guide in making informed decisions in mitigating a population-structured disease transmission under limited resources.

Multi-Faceted Analysis of COVID-19 Epidemic in Korea Considering Omicron Variant: Mathematical Modeling-Based Study.

BACKGROUND: The most recent variant of concern, omicron (B.1.1.529), has caused numerous cases worldwide including the Republic of Korea due to its fast transmission and reduced vaccine effectiveness. METHODS: A mathematical model considering age-structure, vaccine, antiviral drugs, and influx of the omicron variant was developed. We estimated transmission rates among age groups using maximum likelihood estimation for the age-structured model. The impact of non-pharmaceutical interventions (NPIs; in community and border), quantified by a parameter µ in the force of infection, and vaccination were examined through a multi-faceted analysis. A theory-based endemic equilibrium study was performed to find the manageable number of cases according to omicron- and healthcare-related factors. RESULTS: By fitting the model to the available data, the estimated values of µ ranged from 0.31 to 0.73, representing the intensity of NPIs such as social distancing level. If µ < 0.55 and 300,000 booster shots were administered daily from February 3, 2022, the number of severe cases was forecasted to exceed the severe bed capacity. Moreover, the number of daily cases is reduced as the timing of screening measures is delayed. If screening measure was intensified as early as November 24, 2021 and the number of overseas entrant cases was contained to 1 case per 10 days, simulations showed that the daily incidence by February 3, 2022 could have been reduced by 87%. Furthermore, we found that the incidence number in mid-December 2021 exceeded the theory-driven manageable number of daily cases. CONCLUSION: NPIs, vaccination, and antiviral drugs influence the spread of omicron and number of severe cases in the Republic of Korea. Intensive and early screening measures during the emergence of a new variant is key in controlling the epidemic size. Using the endemic equilibrium of the model, a formula for the manageable daily cases depending on the severity rate and average length of hospital stay was derived so that the number of severe cases does not surpass the severe bed capacity.

THE PREVALENCE OF COLONIC POLYPS IN PATIENTS WITH ACROMEGALY: A CASE-CONTROL, NESTED IN A COHORT COLONOSCOPIC STUDY.

OBJECTIVE: Acromegaly is associated with an increased risk of colonic polyps. The magnitude of such risk is controversial, and the characteristics that distinguish patients who develop polyps from those who do not are not well established. This study was performed to determine the prevalence of colonic polyps upon the diagnosis of acromegaly and to compare the clinical and biochemical features of patients with and without polyps. METHODS: Out of 165 patients who underwent a full colonoscopy upon diagnosis of acromegaly, 53 were found to harbor colonic lesions (cases), whereas the remaining 112 were used as controls. Demographic, clinical, and biochemical characteristics were compared between the 2 groups. RESULTS: The prevalence of colonic polyps was 32%, with an estimated relative risk of 6.21 (95% confidence interval [CI] 4.08-9.48). Adenomatous and nonadenomatous polyps were found in 22 and 31 patients, respectively. The most common location was the descending colon. Compared to patients without polyps, subjects with polyps were somewhat older and had significantly higher insulin-like growth factor-1 (IGF-1) levels and a higher prevalence of diabetes. Upon multivariate analysis, only IGF-1 level at diagnosis remained significantly associated with colonic polyps in general and with hyperplastic polyps in particular. CONCLUSION: Acromegaly is associated with an elevated risk of developing colonic polyps, particularly, distally located hyperplastic lesions. Except for a higher IGF-1 level at diagnosis, no distinctive clinical or biochemical features can be found among those who develop polyps compared to those who do not. ABBREVIATIONS: CI = confidence interval GH = growth hormone IGF-1 = insulin-like growth factor 1 IQR = inter-quartile range RR = relative risk ULN = upper limit of normal.

LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

OBJECTIVE: Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. METHODS: We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. RESULTS: Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. CONCLUSION: The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. ABBREVIATIONS: ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal.

Giant prolactinomas larger than 60 mm in size: a cohort of massive and aggressive prolactin-secreting pituitary adenomas.

OBJECTIVES: Prolactin (PRL)-secreting macroadenomas usually measure between 10 and 40 mm. Giant (adenoma size ≥40 mm) PRL-tumors are not common, and larger prolactinomas (maximal diameter ≥60 mm) are rare, and their management outcomes have not been well characterized. METHODS: We have identified 18 subjects (16 men, 2 females) with giant PRL-adenomas (size ≥60 mm; PRL > 1000 ng/ml) and summarized their characteristics and response to treatment. RESULTS: Mean age was 36.3 ± 13.5 years (range 12-59 years). Mean adenoma size was 71.8 ± 10.2 mm (60-92 mm). Complaints at presentation included headaches in 11 patients, visual deterioration in 9, sexual dysfunction in 9 males, and behavioral changes in two. Fourteen (78 %) had visual field defects. Mean PRL at presentation was 28,465 ng/ml (range 1300-270,000). All patients were treated with cabergoline (3.9 ± 2.0 mg/week), except for one who received bromocriptine. Treatment achieved PRL normalization in 11/18 patients within a median interval of 20 months. Visual improvement occurred in 12/14 patients with pre-treatment visual abnormalities. Nine patients underwent surgery (transsphenoidal, 7; transcranial, 2). None of the seven patients with elevated PRL before surgery achieved remission post-operatively. After a follow-up of 7.8 ± 5.1 years, 15/18 patients had significant adenoma shrinkage. Eleven patients are normoprolactinemic, 3 are partially controlled (PRL < 3 × ULN), and 4 remain with significantly elevated PRL. Most patients reported disappearance or improvement of their complaints. CONCLUSIONS: These enormous PRL-adenomas are invasive but respond fairly well to medical treatment. Long-term therapy with high dose cabergoline together with a pituitary surgery in some patients was the key for their successful management, achieving biochemical and clinical remission in most patients.

Pituitary apoplexy in nonfunctioning pituitary macroadenomas: a case-control study.

OBJECTIVE: Pituitary apoplexy (PA) is an endocrinologic emergency characterized by headache, visual abnormalities, and hemodynamic instability in the context of hemorragic infarction of a pituitary adenoma. Our goal was to estimate the incidence, precipitating factors, clinical characteristics, and outcome of PA in a cohort of patients with nonfunctioning pituitary macroadenomas (NFPMAs). METHODS: A retrospective, case-control study of 46 patients with PA and 47 controls matched for age, gender, and tumor invasiveness. Clinical, hormonal, and tumoral charactersitics, as well as the presence of potential precipitating factors and long-term outcome were evaluated using both bivariate and multivariate analysis. RESULTS: The prevalence of PA was 8%. Cases and controls were similar in regards to the prevalence of diabetes, hypertension, use of antiplatelet agents, and the presence of headaches and visual field defects. Oculomotor paralysis was present in 18% of cases and in none of the controls (P = .001). Prior use of dopamine agonists was significantly more frequent among cases than in controls on both bivariate and multivariate analysis. Pituitary hormone deficiencies were more common among cases than in controls on bivariate but not on multivariate analysis. Early and late surgical treatment was carried out in 11 and 25 patients, respectively; 11 patients were managed conservatively. Visual and endocrine outcomes were similar among the 3 groups. CONCLUSION: PA represents a life-threatening medical emergency. Prior use of dopamine agonists and the presence of oculomotor abnormalities clearly distinguished patients with NFPMA who developed PA from those who did not.

Non-CG DNA methylation and MeCP2 stabilize repeated tuning of long genes that distinguish closely related neuron types.

The extraordinary diversity of neuron types in the mammalian brain is delineated at the highest resolution by subtle gene expression differences that may require specialized molecular mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and utilize neuron-enriched non-CG DNA methylation (mCA) together with the Rett syndrome protein, MeCP2, to control gene expression, but the function of these unique gene structures and machinery in regulating finely resolved neuron type-specific gene programs has not been explored. Here, we employ epigenomic and spatial transcriptomic analyses to discover a major role for mCA and MeCP2 in maintaining neuron type-specific gene programs at the finest scale of cellular resolution. We uncover differential susceptibility to MeCP2 loss in neuronal populations depending on global mCA levels and dissect methylation patterns and intragenic enhancer repression that drive overlapping and distinct gene regulation between neuron types. Strikingly, we show that mCA and MeCP2 regulate genes that are repeatedly tuned to differentiate neuron types at the highest cellular resolution, including spatially resolved, vision-dependent gene programs in the visual cortex. These repeatedly tuned genes display genomic characteristics, including long length, numerous intragenic enhancers, and enrichment for mCA, that predispose them to regulation by MeCP2. Thus, long gene regulation by the MeCP2 pathway maintains differential gene expression between closely-related neurons to facilitate the exceptional cellular diversity in the complex mammalian brain.

Identifying patterning behavior in a plant infestation of insect pests.

In this study, we developed a mechanistic model formulated as a system of reaction-diffusion equations (RDE) to explore the spatiotemporal dynamics of a theoretical pest with a tillering host plant in a controlled rectangular plant field. Local perturbation analysis, a recently developed method of analysis for wave propagation, was utilized to determine patterning regimes resulting from the local and global behaviors of the slow and fast diffusing components of the RDE system, respectively. Turing analysis was done to show that the RDE system does not exhibit Turing patterns. With bug mortality as the bifurcation parameter, regions with oscillations and stable coexistence of the pest and tillers were identified. Numerical simulations illustrate the patterning regimes in 1D and 2D settings. The oscillations suggest that recurrences in pest infestation is possible. Moreover, simulations showed that patterns produced in the model are strongly influenced by the pests' homogeneous dynamics inside the controlled environment.

Risk estimation of lifted mask mandates and emerging variants using mathematical model.

Background: More than half of the population in Korea had a prior COVID-19 infection. In 2022, most nonpharmaceutical interventions, except mask-wearing indoors, had been lifted. And in 2023, the indoor mask mandates were eased. Methods: We developed an age-structured compartmental model that distinguishes vaccination history, prior infection, and medical staff from the rest of the population. Contact patterns among hosts were separated based on age and location. We simulated scenarios with the lifting of the mask mandate all at once or sequentially according to the locations. Furthermore, we investigated the impact of a new variant assuming that it has higher transmissibility and risk of breakthrough infection. Results: We found that the peak size of administered severe patients may not exceed 1100 when the mask mandate is lifted everywhere, and 800 if the mask mandate only remains in the hospital. If the mask mandate is lifted in a sequence (except hospital), then the peak size of administered severe patients may not exceed 650. Moreover, if the new variant has both higher transmissibility and immune reduction, the effective reproductive number of the new variant is approximately 3 times higher than that of the current variant, and additional interventions may be needed to keep the administered severe patients from exceeding 2,000, which is the critical level we set. Conclusion: Our findings showed that the lifting of the mask mandate, except in hospitals, would be more manageable if implemented sequentially. Considering a new variant, we found that depending on the population immunity and transmissibility of the variant, wearing masks and other interventions may be necessary for controlling the disease.

Modelling the effects of social distancing, antiviral therapy, and booster shots on mitigating Omicron spread.

As the COVID-19 situation changes because of emerging variants and updated vaccines, an elaborate mathematical model is essential in crafting proactive and effective control strategies. We propose a COVID-19 mathematical model considering variants, booster shots, waning, and antiviral drugs. We quantify the effects of social distancing in the Republic of Korea by estimating the reduction in transmission induced by government policies from February 26, 2021 to February 3, 2022. Simulations show that the next epidemic peak can be estimated by investigating the effects of waning immunity. This research emphasizes that booster vaccination should be administered right before the next epidemic wave, which follows the increasing waned population. Policymakers are recommended to monitor the waning population immunity using mathematical models or other predictive methods. Moreover, our simulations considering a new variant's transmissibility, severity, and vaccine evasion suggest intervention measures that can reduce the severity of COVID-19.

Optimal selection of COVID-19 vaccination sites in the Philippines at the municipal level.

In this work, we present an approach to determine the optimal location of coronavirus disease 2019 (COVID-19) vaccination sites at the municipal level. We assume that each municipality is subdivided into smaller administrative units, which we refer to as barangays. The proposed method solves a minimization problem arising from a facility location problem, which is formulated based on the proximity of the vaccination sites to the barangays, the number of COVID-19 cases, and the population densities of the barangays. These objectives are formulated as a single optimization problem. As an alternative decision support tool, we develop a bi-objective optimization problem that considers distance and population coverage. Lastly, we propose a dynamic optimization approach that recalculates the optimal vaccination sites to account for the changes in the population of the barangays that have completed their vaccination program. A numerical scheme that solves the optimization problems is presented and the detailed description of the algorithms, which are coded in Python and MATLAB, are uploaded to a public repository. As an illustration, we apply our method to determine the optimal location of vaccination sites in San Juan, a municipality in the province of Batangas, in the Philippines. We hope that this study may guide the local government units in coming up with strategic and accessible plans for vaccine administration.

Extracellular proteins OSM-7 and OSM-8 are required for stress response gene regulation at all post-embryonic stages.

Nematode cuticles are extracellular matrices (ECMs) that function as structural support and permeability barriers. Genetic disruption of specific cuticle collagen structures or secreted epidermal proteins in C. elegans activates stress response genes in epithelial cells suggesting the presence of an extracellular damage signaling mechanism. Cuticles are replaced during development via molting but investigations of extracellular signaling to stress responses have focused on adults. In our current study, we measured cuticle phenotypes and stress response gene expression in all post-embryonic stages of mutant strains for a collagen and two secreted epidermal proteins to gain insights into developmental patterns.

A mathematical model of the dynamics of lymphatic filariasis in Caraga Region, the Philippines.

Despite being one of the first countries to implement mass drug administration (MDA) for elimination of lymphatic filariasis (LF) in 2001 after a pilot study in 2000, the Philippines is yet to eliminate the disease as a public health problem with 6 out of the 46 endemic provinces still implementing MDA for LF as of 2018. In this work, we propose a mathematical model of the transmission dynamics of LF in the Philippines and a control strategy for its elimination using MDA. Sensitivity analysis using the Latin hypercube sampling and partial rank correlation coefficient methods suggests that the infected human population is most sensitive to the treatment parameters. Using the available LF data in Caraga Region from the Philippine Department of Health, we estimate the treatment rates r 1 and r 2 using the least-squares parameter estimation technique. Parameter bootstrapping showed small variability in the parameter estimates. Finally, we apply optimal control theory with the objective of minimizing the infected human population and the corresponding implementation cost of MDA, using the treatment coverage γ as the control parameter. Simulation results highlight the importance of maintaining a high MDA coverage per year to effectively minimize the infected population by the year 2030.

Genomic signatures of Lake Erie bacteria suggest interaction in the Microcystis phycosphere.

Microbial interactions in harmful algal bloom (HAB) communities have been examined in marine systems, but are poorly studied in fresh waters. To investigate HAB-microbe interactions, we isolated bacteria with close associations to bloom-forming cyanobacteria, Microcystis spp., during a 2017 bloom in the western basin of Lake Erie. The genomes of five isolates (Exiguobacterium sp. JMULE1, Enterobacter sp. JMULE2, Deinococcus sp. JMULE3, Paenibacillus sp. JMULE4, and Acidovorax sp. JMULE5.) were sequenced on a PacBio Sequel system. These genomes ranged in size from 3.1 Mbp (Exiguobacterium sp. JMULE1) to 5.7 Mbp (Enterobacter sp. JMULE2). The genomes were analyzed for genes relating to critical metabolic functions, including nitrogen reduction and carbon utilization. All five of the sequenced genomes contained genes that could be used in potential signaling and nutrient exchange between the bacteria and cyanobacteria such as Microcystis. Gene expression signatures of algal-derived carbon utilization for two isolates were identified in Microcystis blooms in Lake Erie and Lake Tai (Taihu) at low levels, suggesting these organisms are active and may have a functional role during Microcystis blooms in aggregates, but were largely missing from whole water samples. These findings build on the growing evidence that the bacterial microbiome associated with bloom-forming algae have the functional potential to contribute to nutrient exchange within bloom communities and interact with important bloom formers like Microcystis.

Explicit solution of a Lotka-Sharpe-McKendrick system involving neutral delay differential equations using the r-Lambert W function.

Structured population models, which account for the state of individuals given features such as age, gender, and size, are widely used in the fields of ecology and biology. In this paper, we consider an age-structured population model describing the population of adults and juveniles. The model consists of a system of ordinary and neutral delay differential equations. We present an explicit solution to the model using a generalization of the Lambert W function called the r-Lambert W function. Numerical simulations with varying parameters and initial conditions are done to illustrate the obtained solution. The proposed method is also applied to an insect population model with long larval and short adult phases.

Expression of the growth hormone receptor isoforms and its correlation with the metabolic profile in morbidly obese subjects.

BACKGROUND AND AIM OF THE STUDY: Given the lipolytic effect of GH and its potential role in determining adipose tissue distribution, we evaluated the expression of the GH hormone receptor (GHR) isoforms in patients with morbid obesity seeking associations with metabolic parameters. METHODS: 262 morbidly obese subjects (mean age 42.5 ± 11 years, 75% women) underwent PCR-genotyping of the exon 3 GHR polymorphism. In 17 of these subjects, who proved to be heterozygous for the exon 3 genotype (+3/-3), subcutaneous and visceral adipose tissue was obtained during bariatric surgery; total RNA was extracted, reversely transcribed, and the different isoforms of the GHR (exon 3 containing and lacking flGHR as well as the trGHR) were PCR-amplified using specific primers. RESULTS: 27% were +3/+3 homozygous, 20% -3/-3 homozygous and 53% were +3/-3 heterozygous. Compared to subjects homozygous for the +3 genotype, homozygous and heterozygous carriers of the -3 genotype were significantly heavier and tended to have a higher HOMA 2-IR. Expression of the flGHR and trGHR mRNA was demonstrated in all evaluated samples of subcutaneous and visceral adipose tissue from the 17 patients. The exon 3+ isoform was expressed in all adipose tissue samples, whereas only six subjects expressed the 3- isoform as well. The only distinctive feature of these six patients was a higher HbA1c. CONCLUSIONS: The heterozygous GHR +3/-3 genotype is more prevalent in subjects with morbid obesity. Patients expressing the exon +3 and exon -3 isoforms in adipose tissue had a higher HbA1c, than those expressing only the exon -3 isoform.

Helicobacter pylori y enfermedades alérgicas en niños: un estudio de casos y controles

Introducción: En las dos últimas décadas, se ha explorado el rol de la infección por Helicobacter pylori en la génesis de las enfermedades alérgicas, obteniéndose datos que apoyan la idea de que podría jugar un papel importante en el desarrollo de la alergia. Objetivo: Identificar la asociación entre Helicobacter pylori y enfermedades alérgicas. Materiales y métodos: Estudio de casos y controles prospectivo realizado en la Clínica "Santa Cruz" (Barquisimeto, Estado Lara, Venezuela), entre junio 2022 y junio 2023, donde se compararon 65 niños con enfermedades alérgicas con 130 controles sanos, con edades entre 2 y 15 años, que acudieron a consulta ambulatoria de rutina. Fueron comparadas variables demográficas, parto por cesárea, antecedentes familiares de alergias, tiempo de lactancia materna, exposición al humo de tabaco, mascotas, obesidad, porcentaje de eosinófilos y test de Helicobacter pylori positivo en heces con la presencia de enfermedades alérgicas como variable dependiente. Se utilizó: análisis bivariable y regresión logística binaria. Resultados: Los factores asociados significativamente a enfermedades alérgicas fueron: antecedentes familiares de alergia, tiempo de lactancia materna menor a 12 meses, y test de Helicobacter pylori positivo en heces. Fueron identificados como predictores independientes asociados a enfermedades alérgicas: antecedentes familiares de alergia (RO=2,345; IC95%: 1,245 - 4,416; p = 0,008) y test de Helicobacter pylori positivo en heces (RO=2,072; IC95%: 1,090 - 3,939; p = 0,026). Conclusión: La presencia de antecedentes familiares de alergia y test de Helicobacter pylori positivo en heces fueron identificados como variables independientes asociadas a enfermedades alérgicas.

Introduction: In the last two decades, the role of Helicobacter pylori infection in the genesis of allergic diseases has been explored, showing data supporting the idea that it could play an important role in the development of allergy. Objective: To identify the association between Helicobacter pylori and allergic diseases. Materials and methods: This was a prospective case-control study carried out at the "Santa Cruz" Clinic (Barquisimeto, Lara State, Venezuela), between June 2022 and June 2023, where 65 children with allergic diseases were compared with 130 healthy controls, aged between 2 and 15 years old, who presented for routine outpatient consultation. Demographic variables, cesarean delivery, family history of allergies, breastfeeding time, exposure to tobacco smoke, pets, obesity, percentage of eosinophils and a positive Helicobacter pylori test in feces were compared with the presence of allergic diseases as a dependent variable. Bivariate analysis and binary logistic regression were used. Results: Factors significantly associated with allergic diseases were: family history of allergy, breastfeeding time of less than 12 months, and positive Helicobacter pylori test in feces. The following were identified as independent predictors associated with allergic diseases: family history of allergy (OR=2.345; 95%CI: 1.245 - 4.416; p = 0.008) and positive Helicobacter pylori test in stool (OR=2.072; 95%CI: 1.090 - 3.939; p = 0.026). Conclusions: The presence of a family history of allergy and a positive Helicobacter pylori test in stool were identified as independent variables associated with allergic diseases.

Prevalence, Clinical and Biochemical Spectrum, and Treatment Outcome of Acromegaly With Normal Basal GH at Diagnosis.

Context: The term micromegaly has been used to describe a subset of patients who have elevated IGF-1 levels but apparently normal basal GH (bGH) concentrations and often a glucose-suppressed GH of <1 ng/mL. Objective: To evaluate the prevalence, clinical spectrum, and therapeutic outcome of acromegaly with normal bGH at diagnosis. Design and Methods: Retrospective analysis of a cohort of patients with acromegaly diagnosed and treated at a tertiary care center. Results: A cohort of 528 patients with acromegaly was stratified according to bGH at diagnosis: group 1, <2 ng/mL, n = 16; group 2, 2 to 9.9 ng/mL, n = 202; group 3, 10 to 99 ng/mL, n = 294; and group 4, ≥100 ng/mL, n = 16. Patients in group 1 (normal bGH) constituted 3% of the total cohort and were significantly older and more likely to be male than patients in the other groups. The frequency of acromegalic symptoms, signs, and comorbidities was similar between the four patient groups. Patients in group 1 more often harbored microadenomas (75%) and had significantly lower median IGF-1 and postglucose GH levels. Surgical success rates were similar between patients from groups 1 (53.8%), 2 (54.1%), and 3 (36.9%), whereas only 13.3% of patients in group 4 achieved remission. Conclusion: Normal bGH acromegaly is uncommon in real life. These patients have some distinctive features that argue against this being simply acromegaly in its early stages.

Treatment of multiresistant prolactinomas with a combination of cabergoline and octreotide LAR.

BACKGROUND AND OBJECTIVES: Dopamine agonist (DA)-resistant prolactinomas are rare but they constitute a real challenge, since there are few therapeutic alternatives left for these patients. DESIGN AND SETTING: Proof-of-concept study at a tertiary care, referral center. PATIENTS AND METHODS: The studied population consisted of five patients (one female and four males, mean age at diagnosis 23.5 ± 19) with macroprolactinomas with persistent hyperprolactinemia and/or tumor mass despite high doses of cabergoline (CBG) and pituitary surgery, to whom 20 mg monthly of octreotide LAR was added for 6-13 months. Response was evaluated by measuring prolactin (PRL) levels and by magnetic resonance imaging. Immunohistochemistry (IHC) for pituitary hormones, Ki-67, and somatostatin receptor subtypes 2 and 5 was (SSTR2 and 5) was available in two of the subjects. RESULTS: The addition of octreotide LAR to ongoing CBG treatment had no effect on either PRL levels or tumor size in three patients. In two of the five patients, combination treatment resulted in a significant reduction in PRL concentrations (from 7643 to 200 ng/mL and from 2587 to 470 ng/mL) as well as in adenoma size (93% reduction). IHC evaluation of tumor samples from two patients (a responder and a non-responder) revealed positive immunostaining for PRL and SSTR5 but not for other pituitary hormones or for SSTR2. CONCLUSIONS: The addition of a somatostatin analog to ongoing CBG treatment may be effective in some patients with DA-resistant macroprolactinomas, independently of the adenoma's SSTR expression profile.