Snyder-Robinson syndrome: differential diagnosis of osteogenesis imperfecta.

Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis.

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10(-8) in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.

Importance of in situ preservation of parathyroid glands during total thyroidectomy.

BACKGROUND: Parathyroid failure is the most common complication after total thyroidectomy but factors involved are not completely understood. Accidental parathyroidectomy and parathyroid autotransplantation resulting in fewer than four parathyroid glands remaining in situ, and intensity of medical treatment of postoperative hypocalcaemia may have relevant roles. The aim of this study was to determine the relationship between the number of parathyroid glands remaining in situ and parathyroid failure after total thyroidectomy. METHODS: Consecutive patients undergoing first-time total thyroidectomy were studied prospectively, recording the number of Parathyroid Glands Remaining In Situ (PGRIS = 4 - (glands autografted + glands in the specimen)) and the occurrence of postoperative hypocalcaemia, and protracted and permanent hypoparathyroidism. Demographic, disease-related, laboratory and surgical variables were recorded. Patients were classified according to the PGRIS number into group 1-2 (one or two PGRIS), group 3 (three PGRIS) and group 4 (all four glands remaining in situ), and were followed for at least 1 year. RESULTS: A total of 657 patients were included, 43 in PGRIS group 1-2, 186 in group 3 and 428 in group 4. The prevalence of hypocalcaemia, and of protracted and permanent hypoparathyroidism was inversely related to the PGRIS score (group 1-2: 74, 44 and 16 per cent respectively; group 3: 51·1, 24·7 and 6·5 per cent; group 4: 35·3, 13·1 and 2·6 per cent; P < 0·001). Intact parathyroid hormone concentrations at 24 h and 1 month were inversely correlated with PGRIS score (P < 0·001). Logistic regression identified PGRIS score as the most powerful variable influencing acute and chronic parathyroid failure. In addition, a normal-high serum calcium concentration 1 month after thyroidectomy influenced positively the recovery rate from protracted hypoparathyroidism in all PGRIS categories. CONCLUSION: In situ parathyroid preservation is critical in preventing permanent hypoparathyroidism after total thyroidectomy. Active medical treatment of postoperative hypocalcaemia has a positive synergistic effect.

Prospective study on loss of signal on the first side during neuromonitoring of the recurrent laryngeal nerve in total thyroidectomy.

BACKGROUND: Staged thyroidectomy has been recommended when loss of the signal from intraoperative nerve monitoring is observed after first-side dissection of the recurrent laryngeal nerve. There is no high-quality evidence supporting this recommendation. In addition, it is not clear whether signal loss predicts postoperative vocal cord paralysis. METHODS: This was a prospective observational study of consecutive adult patients undergoing neuromonitored total thyroidectomy for either malignancy or multinodular goitre. The prevalence of first-side loss of signal was recorded. Surgery was completed, and vagus and laryngeal nerves on the first side were rechecked at the end of the procedure. RESULTS: Two-hundred and ninety patients were included. Loss of signal on the first side was noted in 16 procedures (5.5 per cent). Thyroidectomy was completed and, at retesting, 15 of 16 initially silent nerves recovered an electromyographic signal with a mean(s.d.) amplitude of 132(26) mcV. Mean time to recovery was 20.2 (range 10-35) min. In no patient was the signal lost on the opposite side. Only three of 15 nerves with a recovered signal were associated with transient vocal cord dysfunction. CONCLUSION: After loss of signal of the recurrent laryngeal nerve dissected initially, there was a 90 per cent chance of intraoperative signal recovery. In this setting, judicious bilateral thyroidectomy can be performed without risk of bilateral recurrent nerve paresis.

[ANALYSIS OF FACTORS INVOLVED IN THE DEVELOPMENT OF HUMORAL RESPONSE TO VACCINATION AGAINST SARS-COV-2 IN PATIENTS WITH RHEUMATIC PATHOLOGY UNDER BIOLOGICAL TREATMENT.] / ANÁLISIS DE FACTORES IMPLICADOS EN EL DESARROLLO DE RESPUESTA HUMORAL A LA VACUNACIÓN FRENTE A SARS-COV-2 EN PACIENTES CON PATOLOGÍA REUMÁTICA EN TRATAMIENTO BIOLÓGICO.

BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.

Analysis of factors involved in the development of humoral response to vaccination against SARS-CoV-2 in patients with rheumatic pathology under biological treatment.

BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20 mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Are there differences between ceftolozane/tazobactam and ceftazidime/avibactam in treating patients with complicated abdominal infections? Evidence from clinical trials.

Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are new possibilities of antimicrobial treatment that combined a ß-lactam with a ß-lactamase inhibitor. The United States (US) and European regulatory agencies approved their clinical use in adults with complicated intra-abdominal infections. This study aims to know if one of the two antibiotics obtain better efficacy in adults with complicated intra-abdominal infections and by specific pathogens such as P. aeruginosa or E. coli. A search of all trials in MEDLINE, Scopus, and Web of Science comparing a C/T or CZA based antimicrobial regimen with other treatments in patients with intraabdominal infections until August 2021 was performed. To make indirect comparisons, we used a frequentist approach using the R package netmeta.The effects have been expressed through the relative risk (RR) with its confidence interval. Considering the clinical cure and failure rates between the different trial populations (mMITT, CE, ME) and the mortality at the end of the study, we have not found significant differences between CZA and C/T. In the case of Pseudomonas, the RR of treatment failure between these two antibiotics is 1 (95% CI 0.55-1.18). In the case of E. Coli, although it seems that CZA would have a worse result than C/T, differences did not reach statistical significance (RR1.06; 95% CI 0.9-1.14). In conclusion, we have not found statistically significant differences between ceftolozane-tazobactam and ceftazidime-avibactam in treating cIAI. In regards to E. Coli, our results do not reach significance, but it would be possible that C/T and meropenem had better results than CZA. Perhaps new trials would allow a better profile of the role in different types of patients or infections caused by specific microorganisms in the future.

Outcome of protracted hypoparathyroidism after total thyroidectomy.

BACKGROUND: Although the variables that influence the development of post-thyroidectomy hypocalcaemia are now better understood, the risk factors and long-term outcome of persistent hypoparathyroidism (HPP) are poorly defined. A retrospective review of a prospective protocol for the management of post-thyroidectomy hypocalcaemia was performed. METHODS: Patients with a serum calcium level below 8 mg/dl (2 mmol/l) 24 h after total thyroidectomy were prescribed oral calcium with or without calcitriol and followed for at least 1 year. Protracted HPP was defined as an intact parathyroid hormone (iPTH) level below 13 pg/ml and need for calcium medication at 1 month after thyroidectomy. RESULTS: Of 442 patients (343 with goitre, 99 with carcinoma) undergoing total thyroidectomy, 222 (50.2 per cent) developed postoperative hypocalcaemia. Eleven patients were lost to follow-up. Parathyroid function recovered in 131 patients within 1 month and 80 developed protracted HPP, which was associated with lymphadenectomy, fewer than three glands left in situ and incidental parathyroidectomy. Parathyroid function recovered within 1 year in 78 per cent of patients with protracted HPP. Factors associated with late recovery of parathyroid function were higher serum calcium and low but detectable iPTH levels 1 month after surgery. These factors were associated with higher calcitriol and calcium dosages at hospital discharge. Parathyroid autotransplantation did not protect against permanent HPP. CONCLUSION: Higher serum calcium levels at 1 month after total thyroidectomy are associated with recovery of parathyroid function. It is hypothesized that intensive medical treatment of hypocalcaemia-'parathyroid splinting'-may improve the outcome of patients with protracted HPP.

Effect of parathyroidectomy for primary hyperparathyroidism on bone mineral density in postmenopausal women.

BACKGROUND: The bone mineral density (BMD) response to parathyroidectomy is heterogeneous and difficult to predict. Available data come from mixed populations of men and women, of different age and degrees of disease severity, and preoperative BMD loss. METHODS: This was a longitudinal, prospective cohort study of 103 postmenopausal women with osteopenia or osteoporosis at the femoral neck site, successfully operated on for primary hyper parathyroidism. BMD and metabolic variables were recorded before and 1 year after parathyroidectomy. RESULTS: After surgery, there was a 1.3 per cent increase in the median BMD at the femoral neck site (0.615 versus 0.623 g/cm(2); P = 0.001). Overall, positive responses were also observed at total hip (0.4 per cent) and lumbar spine (2.3 per cent) sites. Analysing the individual responses, however, only 45 (46 per cent) of 97 patients showed a significant (at least 3.7 per cent) increase in BMD at the femoral neck site compared with the preoperative value and 52 had a decreased (15) or unchanged (37) femoral neck BMD. Patients who gained BMD were younger, had more severe hyperparathyroidism and better renal function. CONCLUSION: Almost half of the postmenopausal women with hyperparathyroidism and low BMD have a significant remineralization response 1 year after parathyroidectomy. Differential mineralization responses of BMD after surgery appear to be related to severity of primary hyperparathyroidism, age and renal function.

Risk factors for transient vocal cord palsy after thyroidectomy.

BACKGROUND: Transient recurrent laryngeal nerve palsy affects to 5-10 per cent of patients after extracapsular thyroidectomy. This prospective study assessed the impact of surgical injury and extralaryngeal branching of the inferior laryngeal nerve (ILN) on vocal cord dysfunction (VCD). METHODS: Total thyroidectomy or lobectomy was performed in 188 patients, with 302 ILNs at risk. The anatomy of the ILN and degree of injury to the nerve, based on the Laryngeal Nerve Injury Score (LNIS), were recorded. Fibreoptic laryngoscopy was performed a mean(s.d.) of 10.6(4.1) days after thyroidectomy. RESULTS: Some 37.4 per cent of ILNs showed extralaryngeal branching. In all, 10.9 per cent of patients developed VCD; 4.3 per cent had paresis and 6.6 per cent paralysis. All paretic and all but one paralytic cords recovered fully after 61(17) days. VCD was more frequently associated with branched than non-branched ILNs (15.8 versus 8.1 per cent; P = 0.022). Injuries were more common in branched nerves (mean(s.e.m.) total LNIS 0.94(0.08) versus 0.51(0.05); P < 0.001). Branched nerves were more likely to be associated with VCD (odds ratio 2.2 (95 per cent confidence interval 1.1 to 4.5)). CONCLUSION: Branched ILNs suffer more surgical injuries and are twice as likely to be associated with VCD.

Pulse wave velocity and augmentation index are not independently associated with carotid atherosclerosis in patients with rheumatoid arthritis.

Arterial stiffness can enhance cardiovascular risk by increasing atherogenesis or adverse hemodynamic effects. We examined whether the arterial stiffness markers of aortic pulse wave velocity (PWV) and the augmentation index (AIx) are independently associated with carotid artery intima-media thickness (IMT) and plaque in patients with rheumatoid arthritis (RA). PWV and AIx were determined by brachial oscillometry using the Mobil-O-Graph® system and carotid IMT and plaque by ultrasound in 194 consecutive RA patients without established cardiovascular disease, chronic kidney disease, and diabetes at disease onset. In crude analysis, PWV was associated with IMT (ß (95% CI) = 0.04 (0.03 to 0.05), p value < 0.0001) and plaque (OR (95% CI) = 1.69 (1.40 to 2.04), p value < 0.0001). Upon adjustment for the confounders of age, sex, mean blood pressure, body height, and cardiovascular risk factors comprising smoking, the atherogenic index, and diabetes, PWV was not related to IMT (ß (95% CI) = 0.01 (-0.02 to 0.04), p value = 0.5) or plaque (OR (95% CI) = 0.99 (0.96 to 1.01), p value = 0.3). AIx was not associated with IMT in crude (ß (95% CI) = -0.002 (-0.004 to 0.007), p value = 0.2) and adjusted analyses (ß (95% CI) = -0.002 (-0.004 to 0.000), p value = 0.06). AIx was also unrelated to carotid plaque in crude (OR (95% CI) = 1.04 (0.60 to 1.82), p value = 0.9) and adjusted analyses (OR (95% CI) = 0.97 (0.94 to 1.01), p value = 0.1). PWV and AIx are not independently associated with subclinical carotid atherosclerosis in RA.

Influence of nutrition, thyroid hormones, and rectal temperature on in-hospital mortality of elderly patients with acute illness.

The present study was undertaken to investigate the interrelation of nutrition, core temperature, and thyroid function and their influence on survival of patients aged > or = 70 y admitted to the hospital with acute conditions. Sixty-seven patients entered the study. Nutritional state, thyroid function, rectal temperature, and the APACHE II score were recorded at admission. The patients were followed until death or hospital discharge. Patients with a serum albumin concentration < 35 g/L showed a lower triiodothyronine (T3) concentration, a higher reverse triiodothyronine (rT3) concentration, and a higher death rate. Prior weight loss (> or = 10%) did not influence thyroid status but increased the mortality rate. Eleven patients were hypothermic (< 36.5 degrees C) and had a higher mortality, lower total T3 concentration, and higher rT3 concentration than the normothermic or hyperthermic subjects. Serum albumin, body weight, and total T3 concentration were higher in survivors (n = 51) than in nonsurvivors (n = 16). Ongoing weight loss and hypoalbuminemia at admission are highly prevalent in elderly people with acute disease, and influence their clinical outcome. Mild hypothermia was a good predictor of death. Hypoalbuminemia and hypothermia were associated with low T3 and high rT3 values.

A randomized trial on the effect of mannitol on postoperative renal function in patients with obstructive jaundice.

A randomized trial was undertaken to reassess the effectiveness of mannitol in preventing postoperative renal impairment in patients with obstructive jaundice. The study included 31 patients with obstructive jaundice (bilirubin, 3 mg/dl or higher) randomly allocated in two groups to receive (n = 17) or not receive (n = 14) preoperative mannitol. Sixty-five percent of patients had a creatinine clearance below 70 ml/min before surgery. Serum bilirubin and bacteribilia had no relation with preoperative renal function. No relation was found between serum bilirubin value and the percentage fall in postoperative creatinine clearance. Compared with the preoperative values, the postoperative creatinine clearance was significantly impaired in the mannitol group (p = 0.03) and remained almost unaltered in the no-mannitol group. Three patients (9.7%) died of acute renal failure; two were in the mannitol group and one was in the no-mannitol group. Serum fibrin degradation products were not sensitive markers for impending renal failure. There was no significant difference in postoperative serum sodium concentration or in the urinary sodium excretion. Administration of mannitol did not improve the postoperative renal function of jaundiced patients, nor did it prove beneficial in preventing renal failure. Our results suggest that severe disturbances of body-fluid compartments may be the basic mechanism underlying kidney dysfunction in obstructive jaundice and that further water depletion induced by mannitol may indeed prove detrimental.

A new experimental model for secondary hyperparathyroidism.

We have developed an animal model to study the pathogenesis of secondary hyperparathyroidism by inducing stable uremia in Sprague-Dawley rats by selective microligation of terminal branches of the left renal artery, followed by right nephrectomy. After 4 weeks the animals were killed, the parathyroid glands were removed and weighed, and blood samples were obtained. Of 30 rats, uremia developed in 22 (73%; uremic group) and eight (27%) died or did not become uremic. A sham-operated group of 15 rats served as control (control group). Creatinine levels were 1.8 +/- 0.5 mg/dl in the uremic group versus 0.5 +/- 0.1 mg/dl in the control group (p less than 0.0001). Parathyroid glands were hyperplastic in all rats with uremia and were heavier than parathyroid glands of control animals (70.3 +/- 26 vs 19.1 +/- 8 micrograms; p less than 0.0001). In the group with uremia, parathyroid hormone levels were increased over those of the control group (112.6 +/- 13 vs 28.9 +/- 6.2 pg/ml; p less than 0.0001), whereas osteocalcin levels were similar (36.6 +/- 11 vs 37.5 +/- 1 ng/ml). Serum calcium, phosphate, and alkaline phosphatase levels were similar in both groups. Our model can be used to test hypotheses concerning the treatment of secondary hyperparathyroidism and the relative pathogenetic relevance of vitamin D deficiency and phosphate retention.

Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation.

BACKGROUND: Emergency operation in the elderly carries a high risk of death. We investigated the incidence of euthyroid sick syndrome (ESS) and associated nutritional and endocrine abnormalities and their relationship to postoperative outcome in this population. METHODS: Sixty-six patients older than 70 years of age requiring emergency operations were assessed before any therapeutic intervention. Values for thyroid hormones, catecholamines, cortisol, interleukin-6, interleukin-1, C-reactive protein, and the Acute Physiology and Chronic Health Evaluation II score were determined. Nutritional assessment was carried out. Mortality rates and duration of hospital stay were related to ESS and albumin concentrations. RESULTS: ESS was diagnosed in 34 patients (51.50%) and was associated with worse Acute Physiology and Chronic Health Evaluation II scores (10.9 vs 8.6; p = 0.004), hypoalbuminemia (34.7 vs 40.8 gm/L; p = 0.0001), lower triceps skinfold (11.8 vs 14.6 mm; p = 0.03), and higher cortisol and norepinephrine levels (937 vs 741 nmol/L [p = 0.04] and 358 vs 250 pg/ml [p = 0.02], respectively), interleukin-6 plasma concentrations (347 vs 113 pg/ml; p = 0.01), death rate (20% vs 0%; p = 0.02), and length of hospital stay (17.2 vs 11.8 days; p = 0.03). A serum albumin level less than 35 gm/L was virtually always associated with ESS. CONCLUSIONS: ESS is highly prevalent in the elderly with acute surgical problems and is associated with poor nutrition, higher sympathetic response, and worse postoperative outcome. The serum albumin level at admission is a specific marker of ESS.

Medullary thyroid carcinoma. The need for early diagnosis and total thyroidectomy.

Forty patients with medullary thyroid carcinoma and 3 patients with C-cell hyperplasia were studied. Seventeen (40%) cases were sporadic and 26 (60%) were hereditary. Eight patients had type lla multiple endocrine neoplasia, 7 patients had type llb multiple endocrine neoplasia, and 11 patients had familial nonmultiple endocrine neoplasia medullary thyroid carcinoma. Mean follow-up was 6.3 years, with actuarial survival of 88% and 78% at 5 and 10 years (22 and 13 patients), respectively. Seven patients died 1.5 to 10 years after the initial operation; all had advanced disease at presentation (6 with distant, 1 with lymph node metastasis). No deaths occurred in patients with familial nonmultiple endocrine neoplasia medullary thyroid carcinoma, C-cell hyperplasia, or medullary thyroid carcinoma limited to the thyroid gland. Nineteen (68%) of 28 patients diagnosed without screening had regional or distant metastases, whereas only 6 (40%) of 15 patients diagnosed by screening had metastases. Twenty-six patients treated initially with total thyroidectomy and central neck clearance required an average of one reoperation, whereas those with lesser initial procedures required an average of two reoperations. We concluded that (1) familial nonmultiple endocrine neoplasia medullary thyroid carcinoma, early medullary thyroid carcinoma or C-cell hyperplasia, and asymptomatic patients have a good prognosis; (2) screening for medullary thyroid carcinoma by measuring serum calcitonin levels results in earlier diagnosis; and (3) total thyroidectomy and central neck clearance is the procedure of choice for medullary thyroid carcinoma.

Influence of parenteral nutrition on postoperative recovery in an experimental model of peritonitis.

BACKGROUND AND AIMS: There seems to be no clear-cut indications for routine TPN support after major elective surgery. The present study was designed to investigate whether TPN could improve the results of standard surgical care for acute peritonitis (laparotomy plus antibiotics). ANIMALS AND METHODS: Peritonitis was induced in 48 New Zealand rabbits (day -2). On day 0, appendectomy and peritoneal lavage were performed, ceftriaxone (250 mg, i.m./24 h.) was started and animals were randomly assigned to receive regular fluids (RF), glucose-based TPN (G-TPN) or isocaloric fat-based TPN (F-TPN) for 6 days. MAIN OUTCOME MEASURES: Balance studies (days 1-3), s-albumin, thyroid hormones and urinary catecholamines were determined at various points of the experiment. At postmortem, wound infection, residual intra-abdominal infection and laparotomy wound breaking strength were recorded. RESULTS: Peritonitis produced a fall in weight, s-albumin and T3. At day 6, weight-loss was more pronounced in RF than in G-TPN or F-TPN (-7 vs 1.5 vs -1.2%;P=0.0001) but s-albumin and T3 concentrations were similar. Diuresis (377 vs 268 vs 269 mL/3 days; P=0.01) was higher and water balance lower (373 vs 511 vs 480 mL/3 days; P=0.01) in Group RF. Although the differences were not statistically significant (P<0.2), persistent infection and wound breaking strength were slightly worse in the pooled TPN groups compared with the RF group (19 vs 6% and 542 vs 701 g, respectively). CONCLUSIONS: TPN failed to improve relevant biochemical markers and clinical outcome after laparotomy for peritonitis.

Influence of calorie source on the physiological response to parenteral nutrition in malnourished rabbits.

The present study was designed to investigate whether calorie source influences sodium and water metabolism and sympathetic activity during parenteral nutrition (PN). 20 New Zealand rabbits were starved until a mean weight loss of 18% was achieved and then re-fed for 6 days with 2 formulae of PN with different glucose-fat proportions. In the Glucose group (n = 9), 70% of non-protein calories were given as glucose while in the Lipid group (n = 11), 70% of non-protein calories were administered as lipids. Rabbits with a high glucose intake showed significantly higher weight gain (151 +/- 87 vs. 52 +/- 7 g, P = 0.01), water cumulative balance (542 +/- 132 vs. 411 +/- 87 ml; P = 0.02) and urinary metanephrine excretion (0.42 +/- 0.12 vs. 0.30 +/- 0.1 mumol/d, P = .03). Only in this group, urinary metanephrines correlated positively with water and sodium balances (r2 = 0.6; P = 0.02 and r2 = 0.7; P = 0.009 respectively). The Glucose group showed 2 different responses and in a second experiment 10 additional rabbits were added to this group to allow a statistical analysis of the response pattern: half of the animals increased their extracellular water (ECW) compartment while the remaining animals did not. The former group had higher sodium balance (13.9 +/- 8 vs. 4.3 +/- 5; P = 0.004) and wet lung weight (8.9 +/- 0.9 vs. 7.9 +/- 0.8; P < 0.05) after re-feeding and, at the beginning of PN, their serum aldosterone concentration were also higher (221 +/- 11 vs. 130 +/- 47 pmol/l; P < 0.05). In conclusion, glucose based PN appears to increase sympathetic activity and induce spurious weight gain due to markedly positive wate and sodium balances. Plasma aldosterone concentration at the end of starvation period influences sodium retention and ECW expansion during high glucose re-feeding.