Rathke's cleft cyst infections and pituitary abscesses: case series and review of the literature.

PURPOSE: Pituitary abscesses (PAs) are a rare clinical entity which may arise from normal pituitary tissue or underlying lesions within the gland. Rathke's cleft cysts (RCCs) are not commonly associated with the development of PA. METHODS: Retrospective chart review of three patients with PAs within RCCs at a single university center and review of the literature. RESULTS: Three cases are reported. The first case presented with fever and headache and a history of prior surgery due to RCC and a recent respiratory tract infection. The second case had a history of recent skin infections and presented with sudden onset headache and hypopituitarism. In the third case, chronic visual field impairment prompted an ophthalmologic evaluation resulting in a diagnosis of an adenoma and an infected RCC. In all three cases, an endoscopic endonasal approach was performed to drain infected tissue and allowed microbiological identification of gram-positive cocci, followed by treatment with antibiotics for at least three weeks. Cases in the literature are scarce and the diagnosis is usually made intraoperatively due to non-specific manifestations and imaging. PAs arising from underlying pituitary lesions are less common than primary PAs. Differential diagnosis should include pituitary apoplexy, hypophysitis and other cystic lesions. CONCLUSION: PAs occurring in RCCs are infrequent. Clinical manifestations are commonly subacute, without septic symptoms. Imaging is usually non-specific. Preoperative diagnosis is infrequent and a broad differential diagnosis should be considered. Empirical antimicrobial therapy should be initiated and adjusted after obtaining cultures to reduce the rate of recurrence and improve clinical outcomes.

Tumor-induced osteomalacia: experience from a South American academic center.

The majority of tumor-induced osteomalacia cases have been reported in the Northern Hemisphere and Asia. In this first series of South American patients, we show that the clinical presentation and sensitivity of plasmatic fibroblast growth factor 23 and somatostatin analog-based imaging are similar to those described in other populations. INTRODUCTION: Describe the experience of clinical presentation, diagnostic study, and treatment of patients with tumor-induced osteomalacia (TIO) in a South American academic center in comparison to literature. METHODS: Analysis of the records of patients diagnosed with TIO. The clinical presentation, diagnostic studies, and treatment were analyzed. Fibroblast growth factor 23 (FGF23) was measured by ELISA. RESULTS: Six patients were diagnosed with TIO during the studied period. The patients' median age was 53 years (range 22-64). All patients presented with weakness and pain in the extremities. Four experienced fractures during their evolution. The median time to diagnosis was 4.5 years (1-20). Biochemical studies showed hypophosphatemia, median of 1.4 mg/dL (1.2-1.6), with low maximum rates of tubular reabsorption of phosphate adjusted for glomerular filtration rate. FGF23 was elevated in 4/6 patients and inappropriately normal in the other two. In three patients, the location of the tumor was clinically evident and confirmed with anatomical imaging. In the remaining patients, two tumors were located with 68Ga DOTATATE-PET/CT and one with OctreoScan. The causal tumors were located in the lower extremities in five patients and invading the frontal sinus in one patient. In all patients, tumors were successfully removed. Within 14 days, there was normalization of phosphate and FGF23 levels and resolution of clinical symptoms in all patients. In all cases, the histopathology was compatible with a phosphaturic mesenchymal tumor. CONCLUSIONS: The clinical presentation, delay time to diagnosis, FGF23 diagnostic sensitivity and histopathology in this first series of South American patients is similar to those described in other populations. The success of localization by somatostatin analog-based imaging, suggests this may the optimal imaging modality.

Ingestion of paralytic shellfish toxins in a carnivorous gastropod (Chorus giganteus): effects on their elemental composition and reproductive traits.

The producer of paralytic shellfish toxin (PST), Alexandrium catenella, is one of the main generators of HABs in the coasts of Chile. Its presence produces ecological and economic damage, directly affecting filter-feeding organisms, and indirectly to other organism through the trophic chain. The objective of this research was to identify the effect of a toxic diet on the energetic and reproductive parameters of the carnivorous snail Chorus giganteus. Two groups of snails were used, one fed with toxic prey (bivalves fed with A. catenella), and the other fed with non-toxic prey. Both treatments were maintained under these conditions for 63 days, then, elemental composition (C, N) and energy content were estimated, and fecundity parameters were analyzed. The results indicate that snails fed with toxic prey had a lower percentage of C and C/N ratio. The energy content was significantly lower in intoxicated snails. Regarding fecundity parameters, a higher number of egg-masses were produced by toxic snails, however, only 62% of these showed embryonic development, with 57% hatching success. A negative relationship was identified between the mean PST concentration, quantified in snails, and the number of egg-masses produced per aquarium. In the aquarium where the snails had highest average PST concentration (1200 ± 820 µg STX.2HCL eq. Kg-1) there was no oviposition, while egg-masses were only produced by snails in aquaria where the average concentration did not exceed 360 ± 160 µg STX.2HCL eq. Kg-1. It is likely that, with low levels of accumulated PST, C. giganteus activates its oviposition process as a response to toxin-induced stress, generating a higher energy expenditure supported by a redirection of its reserves. However, when the intoxication presents higher levels, the reproductive process could be inhibited, similar to what has been identified in other molluscs.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

AIMS: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. METHODS AND RESULTS: 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). RESULTS: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114). CONCLUSIONS: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Host gene-encoded severe lung TB: from genes to the potential pathways.

We are reporting that the two-locus genotype -2518 macrophage chemoattractant protein (MCP)-1 GG and -1607 matrix metalloproteinase (MMP)-1 2G/2G promotes the expression of hyperinflammation in response to Mycobacterium tuberculosis infection, inducing extensive tissue damage and severe tuberculosis (TB) disease. Carriers of this two-locus genotype have a 13-fold higher chance of developing severe disease and 6.5-fold higher chance of developing permanent lesions, and a 3.864-fold higher chance of delayed response to first-line standardized treatment than carriers of any other relevant combination of genotypes at those two loci. Thus, these persons have an increased likelihood of poor health-related quality of life and of transmitting M. tuberculosis to other members of the community. In addition, through the analysis of human lung tissues, serum/plasma and in vitro experiments, including in vitro infections of THP-1 cells with M. tuberculosis and microarray analysis, we determined that this hyperinflammation state is potentially driven by the MCP-1/MMP-1/PAR-1 pathway. Hence, we are providing markers for the identification of TB cases that may develop severe pulmonary disease and delayed response to treatment, and are providing the basis for development of novel host-targeted clinical interventions to ameliorate the severity of pulmonary TB.

Outcomes of a multidisciplinary mechanical circulatory support network in cardiogenic shock in a centre without heart transplant program: A successful interprofessional coordination model.

BACKGROUND AND OBJECTIVE: Cardiogenic shock (CS) mortality remains very high and mechanical circulatory support (MCS) may provide an effective alternative of treatment in selected patients. The aim of this study is to analyse the results of a multidisciplinary team care program (including anaesthesiologists, cardiologists, cardiothoracic surgeons, and intensivists) in CS patients who required MCS, in a tertiary centre without a heart transplant (HT) program. METHODS: Prospective observational study that sought to analyse the characteristics and survival to discharge predictors in a consecutive CS patients cohort treated with MCS. RESULTS: A total of 48 patients were included. Mean age was 61 ± 14 years. Before MCS, 45.8% of the patients presented with cardiac arrest. A 54.2% 30-day survival and 45.8% overall survival to discharge, was found. Age and vasoactive-inotropic score were independent predictors of mortality. CONCLUSIONS: A multidisciplinary team-care based MCS program in CS patients is feasible and may achieve favourable results in a centre without HT program.

Impact of Diabetes Mellitus and Frailty on Long-Term Outcomes in Elderly Patients with Acute Coronary Syndromes.

OBJECTIVES: Diabetes mellitus (DM) and frailty are common in older patients with acute coronary syndromes (ACS). No data exists about its prognostic impact on long-term outcomes and their possible interaction in this setting. DESIGN: Observational prospective study. SETTING: Multicenter registry conducted in 44 hospitals in Spain. PARTICIPANTS: Consecutive patients with ACS aged 80≥years. MEASUREMENTS: A comprehensive geriatric evaluation was performed during hospitalization, including frailty assessment by the FRAIL score. The impact of DM and frailty on the incidence of mortality/readmission at 24 months was analysed by a Cox regression model. RESULTS: A total of 498 patients were included (mean age 84.3 years). Prevalence of previous DM was 199/498 (40.0%). The rate of frail patients was 135/498 (27.1%). The incidence of mortality/readmission was higher frail patients (HR 2.49) (both p<0.001). In contrast, DM was not significantly associated to a higher rate of outcomes (HR 1.23, p=0.060) in the whole cohort. Among non-frail patients, patients with DM had a similar incidence of mortality or readmission (p=0.959). In contrast, among frail patients, DM was significantly associated with a higher incidence of events (HR 1.51, p=0.034). CONCLUSIONS: Unlike frailty status, DM was not associated to poorer long-term outcome in elderly patients with ACS. Among frail patients the presence of DM seems to provide additional prognostic information.

Human case of swine influenza A (H1N1), Aragon, Spain, November 2008.

A human case of swine influenza A (H1N1) in a 50-year-old woman from a village near Teruel (Aragon, in the north-east of Spain), with a population of about 200 inhabitants, has been reported in November 2008.

Resultados de un programa multidisciplinar de soporte circulatorio mecánico en shock cardiogénico en un centro sin programa de trasplante cardiaco: un modelo exitoso de coordinación entre profesionales / Outcomes of a multidisciplinary mechanical circulatory support network in cardiogenic shock in a centre without heart transplant program: A successful interprofessional coordination model

Antecedentes y objetivo: El shock cardiogénico (SC) conlleva una elevada mortalidad, y algunos pacientes pueden beneficiarse del uso de soporte circulatorio mecánico (SCM). El objetivo de este estudio es analizar los resultados de un programa multidisciplinar (constituido por anestesiología y reanimación, cardiología, cirugía cardiaca y medicina intensiva) de atención a pacientes en SC que precisaron SCM en un hospital terciario sin programa de trasplante cardiaco. (TC). Materiales y métodosEstudio prospectivo observacional que analiza las características y predictores de supervivencia hospitalaria de los pacientes con SC que precisaron SCM. Resultados: Se incluyeron 48 pacientes. Edad media 61±14años. El 45,8% presentaron parada cardiaca previa al implante. La supervivencia a 30días fue del 54,2% y la supervivencia al alta hospitalaria, del 45,8%. La edad y la escala de vasoactivos inotrópicos fueron predictores independientes de mortalidad. Conclusiones: La instauración de un programa multidisciplinar de SCM en un centro sin programa de TC es factible y aplicable a pacientes con SC, con resultados favorables en cuanto a supervivencia hospitalaria.(AU)

Background and objective: Cardiogenic shock (CS) mortality remains very high and mechanical circulatory support (MCS) may provide an effective alternative of treatment in selected patients. The aim of this study is to analyse the results of a multidisciplinary team care program (including anaesthesiologists, cardiologists, cardiothoracic surgeons, and intensivists) in CS patients who required MCS, in a tertiary centre without a heart transplant (HT) program. Methods: Prospective observational study that sought to analyse the characteristics and survival to discharge predictors in a consecutive CS patients cohort treated with MCS. Results: A total of 48 patients were included. Mean age was 61 ± 14 years. Before MCS, 45.8% of the patients presented with cardiac arrest. A 54.2% 30-day survival and 45.8% overall survival to discharge, was found. Age and vasoactive-inotropic score were independent predictors of mortality. Conclusions: A multidisciplinary team-care based MCS program in CS patients is feasible and may achieve favourable results in a centre without HT program.(AU)

Influence of acute unilateral vestibular lesions on the respiratory rhythm after active change of posture in human subjects.

The influence of acute unilateral vestibular lesions on respiratory rhythm after active change of posture, was evaluated by comparing responses from patients with acute vestibular neuritis, with those from normal subjects with minor injuries other than vestibular (e.g. epistaxis, headache) and patients with chronic bilateral vestibular dysfunction. Respiratory movements of the thorax-abdomen were recorded during 5 minutes in supine position, 5 minutes of back-unsupported sitting and 5 minutes of upright stance. Compared to supine position, sitting-up induced different responses in each group (p < 0.05, ANOVA). The healthy subjects showed a consistent decrease in the mean respiratory frequency related to an increase of the expiration time, which was absent in patients with vestibular neuritis. Subjects with minor injuries showed the opposite changes of expiration time and inspiration time with no change of the respiratory frequency and patients with bilateral vestibular dysfunction showed a trend to increase their respiratory frequency. Standing-up did not evoke any further changes in any group. We conclude that the vestibular system modulates the respiratory response to reorientation of the head and trunk to upright position and this influence is reduced during the acute stage of a vestibular lesion.

Identification of most frequent HLA class I antigen specificities in Botswana: relevance for HIV vaccine design.

Since the mid-1990s, southern African countries have been experiencing an expansion of human immunodeficiency virus type 1 (HIV-1) infection caused by HIV-1 subtype C. To facilitate the design of an HLA-based HIV vaccine, we studied the distribution of the HLA class I antigen specificities in Botswana, a southern African country with a high prevalence of HIV infection. Botswana's highly efficient health care system and its central geographical location within southern Africa suggests that it might be an appropriate candidate site for future trials of an HLA-based HIV vaccine. Specificities of HLA class I genes have been investigated in DNA samples obtained from 161 persons of Botswana origin by polymerase chain reaction (PCR) with sequence-specific primers. We identified 4 HLA-A, 7 HLA-B, and 5 HLA-C specificities that were observed at high frequencies in the Botswana population: A30, A02, A23, A68, B58, B72, B42, B8, B18, B44, B45, Cw7, Cw2, Cw17, Cw6, and Cw4. HLA-A30, A02, A23, A68, B58, Cw2, Cw4, Cw6, Cw7, and Cw17 were observed at frequencies of more than 10%. The frequency of HLA-A30 was 27.3%. HLA-B58 (17.9%) was the most frequent generic HLA-B type. Other frequent antigen specificities detected for the HLA-B were B72 (9.6%), B42 (9.3%), B8 (7.4%), B18 (7.4%), B44 (7.4%), and B45 (6.4%). Analysis of haplotype frequencies revealed that haplotypes HLA-A30/HLA-B58 (6.7%), A30/B42 (6.1%), A30/B8 (4.1%), A30/B45 (3.2%), and A23/B58 (2.5%) were the most frequent among two-locus haplotypes. The comparison of HIV-positive patients and noninfected controls for HLA class I specificities confirmed the previously described association of A2/A6802 supertype with resistance to HIV. Our study suggested an increased resistance to HIV infection associated with A68 rather than A2. We also found that the generic HLA-B58 type was associated with increased susceptibility to HIV infection. Our findings suggest that the design of an HLA-based HIV vaccine that includes multiple CTL epitopes restricted by identified common HLA class I specificities might target up to 97.5% of the population in Botswana. The results of this study extend the HLA map to a southern African country that has high rates of HIV and also provide a database for the design of an HLA-based HIV vaccine.

HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos.

The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.

Administration of recombinant human interleukin 12 to chronically SIVmac-infected rhesus monkeys.

With the demonstration that interleukin 12 can enhance natural killer (NK) cell activity and drive CD4+ lymphocytes toward T helper type 1 (Thl) responses, there is a strong rationale for exploring the use of this cytokine as an immunomodulatory therapy in HIV-1-infected individuals. To assess its potential safety and effects on both immune and virologic aspects of HIV-1 infection, recombinant human IL-12 (rhIL-12) was assessed in rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques (SIVmac). The activity of rhIL-12 on rhesus monkey lymphocytes was confirmed with the demonstration that peripheral blood lymphocyte lysis of the NK-sensitive cell line Colo was enhanced by this recombinant cytokine. Further, rhIL-12 was shown to induce interferon-gamma production by rhesus monkey lymphocytes in vitro. Then, in separate studies, two treatment regimens of rhIL-12 were assessed in SIVmac-infected monkeys: a low-dose regimen (0.1 microg/kg, daily for 4 weeks) and a high-dose regimen (2.5 microg/kg, every 3-4 days, for 3 weeks). Both rhIL-12 treatment regimens were well tolerated by these virus-infected animals. The high-dose regimen of rhIL-12 induced transient decreases in circulating lymphocytes in the SIVmac-infected monkeys. Furthermore, no changes in lymphocyte-associated SIVmac DNA or SIVmac plasma RNA levels were seen in the treated monkeys. These studies indicate that short-term treatment with rhIL-12 is well tolerated and causes no measurable changes in virus load in chronically SIVmac-infected rhesus monkeys.

Nucleases in the autolysis of filamentous fungi.

RNase and DNase activities were studied in seven fungi of the subdivisions Ascomycotina, Zygomycotina and Basidiomycotina during their autolysis, and extracellular and intracellular RNase and DNase were found. RNase specific activity reached higher levels than DNase specific activity in the culture liquid and mycelial extract, except in Aspergillus nidulans. Generally maximal RNase specific activities were observed at the onset of autolysis in the culture liquid. In the mycelial extract an increase in this activity with the incubation time was observed, except in A. nidulans and Coriolus versicolor. The highest values of DNase specific activities were found at the third day of autolysis in A. nidulans culture liquid and at the thirtieth day of autolysis in Schizophyllum commune mycelial extract. A possible relationship between the culture liquid pH during the autolysis of the studied fungi and the levels of DNase specific activity was observed.

Magnetic resonance applications in cerebral injury.

CT and MR imaging are complementary in the evaluation of cerebral head trauma. CT is still more useful for the initial evaluation of the acutely unstable patient who has a head injury. However, many lesions are identified by MR imaging such as cortical contusions, small subdural hematomas, and diffuse axonal injuries that may not be seen on CT examinations. In addition, MR angiography can play an important role in the diagnostic evaluation of the trauma patient. MR angiography can be clinically useful in delineating vascular abnormalities such as arterial occlusions, arteriovenous fistulae, dissecting aneurysms, and venous sinus occlusion. In pediatric trauma, MR imaging appears to be superior to CT in assessing head injuries, particularly those due to child abuse.

Simplified technique for subdural pressure monitoring: technical note.

A simplified technique for monitoring intracranial pressure via a subdural catheter is presented. It utilizes a commercially available Silastic catheter inserted through a frontal twist drill approach. Twenty patients have been treated thus far without complication. Advantages over other extraventricular monitoring techniques are presented.

An improved subarachnoid screw for intracranial pressure monitoring. Technical note.

A new subarachnoid screw for monitoring intracranial pressure has been developed incorporating a lock-nut and multiple subarachnoid ports in a low-profile design. This device offers enhanced stability and flexibility.