Analysis of the effects of a delay of surgery in patients with hip fractures: outcome and causes.

This study analyzed characteristics of hip fracture patients who did not undergo surgery within 24 hours after hospitalization, as recommended by the Belgian quality standards. Reasons for delay were analyzed. Delay in surgery for hip fracture was related to the medical condition of the patients. INTRODUCTION: To compare patients with optimal timing to patients with a delay in hip surgery, with respect to outcome (complications (postoperative) and mortality) and reasons for delay. METHODS: A retrospective analysis of medical records compared patients operated on within 24h (Group A) to patients operated on more than 24h after admission (Group B). A follow-up period of 5 years after release or up to the time of data collection was used. Reasons for delay in relation with mortality were analyzed descriptively. Descriptive statistics were used for patient demographics and complications. Relationships causing a delayed surgery and mortality were analyzed using binary logistic regression. Additionally, a survival analysis was provided for overall mortality. RESULTS: Respectively, 536 and 304 patients were included in Group A and B. The most prominent reason for delaying surgery was the patient not being medically fit (20.7%). Surgical delay was associated with more cardiovascular (p = 0.010), more pulmonary (p < 0.001), and less hematologic complications (p=0.037). Thirty-day mortality was higher with increasing age (p < 0.001), with hematologic (p < 0.001) or endocrine-metabolic complications (p = 0.001), and lower when no complications occurred (p = 0.004). Mortality at the end of data collection was higher for patients with delayed surgery (OR = 2.634, p < 0.001), an increased age (p = 0.006), male gender (p < 0.001), institutionalized patients (p = 0.009), pulmonary complication (p = 0.002), and having no endocrine-metabolic complications (p = 0.003). Survival analysis showed better survival for patients operated on within 24h (p < 0.001). CONCLUSIONS: Delayed surgery for patients with hip fractures was associated with bad additional medical conditions. Survival was higher for patients operated on within 24h of admission.

Central diabetes insipidus: beware of Langerhans cell histiocytosis!

Langerhans cell histiocytosis (LCH) is a rare disorder, characterised by a monoclonal proliferation of aberrant histiocytes that accumulate in and infiltrate into different organs. When the hypothalamic-pituitary axis is involved, central diabetes insipidus (CDI) can be its first manifestation. Three cases of LCH with central diabetes insipidus were retrospectively analyzed: Case 1 is a 41-year old female presenting with polyuria and polydipsia. Diabetes insipidus was diagnosed and treated with desmopressin. MRI pituitary showed hypophysitis. Subsequently, she developed bone lesions and a biopsy demonstrated LCH. Case 2 is a 51-year old female presenting in 2009 with polyuria and polydipsia. Diabetes insipidus was diagnosed and treated with desmopressin. MRI pituitary revealed hypophysitis. LCH was suspected because of known pulmonary histiocytosis. Coexisting bone lesions were biopsied and confirmed LCH. Case 3 is a 44-year old female presenting with diabetes insipidus. She was treated with desmopressin as well. MRI of the pituitary gland showed impressive thickening of the infundibulum. A few months later, she developed skin lesions and a biopsy revealed LCH. Conclusively, LCH is a rare, elusive and probably underdiagnosed disease with a broad disease spectrum. Due to infiltration of the hypothalamic-pituitary axis, CDI can be the first manifestation, even before LCH is diagnosed. Therefore, LCH should be considered in the diagnostic workup of CDI.

A new mutation in the calcium-sensing receptor gene causing hypocalcaemia: case report of a father and two sons.

BACKGROUND: Regulation of calcium is mediated by parathyroid hormone (PTH) and 1.25-dihydroxyvitamine D3. The calcium-sensing receptor (CaSR) regulates PTH release by a negative feedback system. Gain-of-function mutations in the CaSR gene reset the calcium-PTH axis, leading to hypocalcaemia. PATIENTS AND METHODS: We analysed a family with hypocalcaemia. The proband was a 47-year-old man (index, patient I1), who presented with paraesthesias in both limbs. He has two sons (patient II1 a nd I I2). The probands' lab results showed: serum calcium of 1.95 mmol/l, albumin 41 g/l, phosphate 0.81 mmol/l and PTH 6.6 ng/l (normal 15-65 ng/l). Based on this analysis, we suspected a hereditary form of hypocalcaemia and performed genetic testing by polymerase chain reaction and Sanger sequencing of the coding regions and intron boundaries of the CaSR gene. Genetic analysis revealed a new heterozygous mutation: c.2195A>G, p.(Asn732Ser) in exon 7. The lab results of patient II1 showed: serum calcium of 1.93 mmol/l, phosphate 1.31 mmol/l, albumin 41 g/l, and PTH 24.3 ng/l. His genotype revealed the same activating mutation and, like his father, he also lost his scalp hair at an early adolescent age. Patient II2 is asymptomatic, and has neither biochemical abnormalities, nor the familial CaSR gene mutation. He still has all his scalp hair. CONCLUSIONS: 1) The c.2195A>G, p.(Asn732Ser) mutation in exon 7 of the CaSR gene leads to hypocalcaemia, and has not been reported before in the medical literature. 2) Possibly, this mutation is linked to premature baldness.

Impact of thyroid autoimmunity in euthyroid women on live birth rate after IUI.

Study question: Does thyroid autoimmunity (TAI) predict live birth rate in euthyroid women after one treatment cycle in IUI patients? Summary answer: TAI as such does not influence pregnancy outcome after IUI treatment. What is known already: The role of TAI on pregnancy outcome in the case of IVF/ICSI is largely debated in the literature. This is the first study to address this issue in the case of IUI. Study design, size, duration: This was a retrospective cohort study. A two-armed study design was performed: patients anti-thyroid peroxidase (TPO)+ and patients anti-TPO-. All patients who started their first IUI cycle in our fertility center between 1 January 2010 and 31 December 2014 were included. After exclusion of those patients with or being treated for thyroid dysfunction, 3143 patients were finally included in the study. Participants/materials, setting, methods: After approval by the institutional review board we retrospectively included all patients who started their first IUI cycle in our center between 1 January 2010 and 31 December 2014 with follow-up of outcome until 31 December 2015. Patients with clinical thyroid dysfunction were excluded (thyroid-stimulating hormone (TSH) <0.01 mIU/l; TSH >5 mIU/l) as were patients under treatment with levothyroxine or anti-thyroid drugs. These patients were then divided into two main groups: patients anti-TPO+ and patients anti-TPO- (= control group). Live birth delivery after 25 weeks of gestation was taken as the primary endpoint of our study. As a secondary endpoint, we evaluated differences in live birth delivery after IUI according to different upper limits of preconception TSH thresholds (<2.5 and <5.0 mIU/l). Furthermore, the influence of thyroid function (TSH, free thyroxine (fT4)), anti-TPO status, age, smoking, BMI, parity, ovarian reserve (anti-mullerian hormone (AMH) and FSH), IUI indication and IUI stimulation on live birth rate was analyzed. Main results and the role of chance: Between-group comparison did not show any significant difference between the anti-TPO+ and anti-TPO- group with respect to live birth delivery-, pregnancy- or miscarriage rate with odds ratio at 1.04 (95% CI: 0.63; 1.69), 0.98 (95% CI: 0.62; 1.55) and 0.74 (95% CI: 0.23; 2.39), respectively. In addition, there were no significant differences in live birth delivery-, pregnancy- or miscarriage rate when comparing subgroups according to TSH level (TSH ≥2.5 mIU/l vs. TSH <2.5 mIU/l) with an odds ratio at 1.05 (95% CI: 0.76; 1.47), 1.04 (95% CI: 0.77; 1.41) and  0.95 (95% CI: 0.47; 1.94), respectively. Limitations, reasons for caution: This study was powered for the primary aim, live birth rate. The limitations of this study are the absence of region-specific reference ranges for thyroid hormones and the absence of follow-up of TSH values during ART and subsequent pregnancy. Moreover, there was a time difference of 5 months between thyroid assessment and the start of stimulation. The area where the study was conducted corresponds to a mild iodine deficient area and data should be translated with caution to areas with different iodine backgrounds. Wider implications of the findings: Our findings indicate comparable pregnancy-, abortion- and delivery rates in women with and without TAI undergoing IUI. Moreover, we were unable to confirm a negative effect of TSH level above 2.5 mIU/l on live birth delivery rate. We therefore believe that advocating Levothyroxine treatment at TSH levels between 2.5 and 4 mIU/l needs to be considered with caution and requires further analysis in a prospective cohort study. Study funding/competing interest(s): No external funding was used for this study. No conflicts of interest are declared.

A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.

OBJECTIVES: The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI). METHODS: An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/µL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/µL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59). RESULTS: For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm. CONCLUSIONS: A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.

A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations.

AIMS: To investigate whether polymorphisms in SLC6A20 are associated with susceptibility to Type 2 diabetes. METHODS: In the Rotterdam Study, a prospective, population-based cohort (n = 5974), 22 tagging polymorphisms with minor allele frequencies>0.05 across SLC6A20 were studied. Replication studies were performed in an independent Dutch case-control study (DiaGene-Rotterdam Study 2 n = 3133), and in a Chinese Han case-control population (n = 2279). A meta-analysis of the results was performed. RESULTS: In the Rotterdam study, the minor alleles of rs13062383, rs10461016 and rs2286489 increased the risk of Type 2 diabetes (hazard ratio 1.37, 95% CI 1.15-1.63, hazard ratio 1.30 95% CI 1.09-1.54 and hazard ratio 1.20, 95% CI 1.07-1.35, respectively). In the DiaGene/Rotterdam Study 2, the A allele of rs13062383 increased the risk of Type 2 diabetes (odds ratio 1.45, 95% CI 1.19-1.76). In the Chinese Han study, the rs13062383 A allele also increased the risk of Type 2 diabetes (odds ratio 1.21, 95% CI 1.03-1.42). Meta-analysis showed a highly significant association of rs13062383 with Type 2 diabetes (odds ratio 1.35, 95% CI 1.21-1.47; P = 3.3 × 10⁻8). CONCLUSIONS: In conclusion, rs13062383 in SLC6A20 increased the susceptibility to Type 2 diabetes in populations with different genetic backgrounds.

Iron deficiency before and after bariatric surgery: the need for iron supplementation.

Hepcidin inhibits the iron export from duodenal cells and liver cells into the plasma and therefore plays a key role in controlling iron homeostasis. In obese patients, elevated cytokine production stimulates hepcidin synthesis, causing iron to be retained as ferritin in e.g. macrophages (functional iron deficiency). In addition, patients often develop iron deficiency after bariatric surgery due to malabsorption, which may cause anaemia and thereby lead to complaints such as fatigue. In these patients, the absorption of iron may be disrupted because the reduction of Fe3+ by gastric acid into Fe2+ (the form that is easily absorbed) is not so effective after stomach reduction. Iron absorption is further reduced after malabsorptive interventions as a result of bypassing the duodenum and the proximal part of the small intestine, where the absorption takes place. Oral iron supplements often have little effect after bariatric surgery. Intravenous supplements of iron can restore the iron status rapidly after bariatric surgery, resulting in fewer symptoms such as fatigue.

Hypogonadism in a patient with mild hereditary haemochromatosis.

Hypogonadism is a potential complication of haemochromatosis, usually seen in patients with severe iron overload and liver cirrhosis. We describe the diagnostic workup of a patient with an early stage of hereditary haemochromatosis, presenting with only mildly elevated liver enzymes and central hypogonadism in the absence of cirrhosis or diabetes, but with concurrent sarcoidosis.

High prevalence of diabetes mellitus in patients with liver cirrhosis.

AIMS: The reported prevalence of Type 2 diabetes mellitus in patients with liver cirrhosis is five times higher than in the general population. However, these data were never adjusted for classical risk factors for Type 2 diabetes. We therefore investigated the association between cirrhosis and Type 2 diabetes and adjusted for known risk factors for Type 2 diabetes. METHODS: We reviewed medical files for presence of Type 2 diabetes and potential confounders in 94 patients with cirrhosis (cases) and compared these with a control group of 107 patients with non-ulcer dyspepsia. Multiple logistic regression analysis was used to adjust for potential confounders. RESULTS: The aetiology of our cirrhosis population was alcohol (59%), viral hepatitis (10%), biliary cirrhosis (3%) or cryptogenic (28%). Prevalence of Type 2 diabetes was significantly higher in patients with cirrhosis than in control subjects: 35/94 (37%) vs. 7/107 (7%) (OR 8.5, 95% CI 3.5­20.2, P < 0.001). After adjustment for age, sex, family history of Type 2 diabetes, alcohol use and BMI, cirrhosis remained significantly associated with Type 2 diabetes (OR 13.6, 95% CI 4.3­42.9, P < 0.001). Most cases of Type 2 diabetes were already diagnosed before diagnosis of cirrhosis (21/35, 60%) or were incidentally found together with cirrhosis (5/35, 14%). CONCLUSIONS: Liver cirrhosis had a strong, independent association with Type 2 diabetes. Classical risk factors such as family history and BMI could not explain the high Type 2 diabetes prevalence in cirrhosis. Therefore, a liver-derived factor might aggravate glucose intolerance and cause Type 2 diabetes in cirrhosis. In addition, Type 2 diabetes might also cause cirrhosis through liver steatosis and fibrosis.

Primary squamous cell carcinoma of the thyroid years after radioactive iodine treatment.

Primary squamous cell carcinoma (SCC) of the thyroid gland is a rare diagnosis, since there is no squamous epithelium in the thyroid gland. SCC of the thyroid is highly aggressive with a poor prognosis. We present a case of primary SCC of the thyroid: this 88-year-old male patient had a history of hyperthyroidism which was treated with radioactive iodine 25 years earlier. Whether this treatment could be related to SCC of the thyroid is not clear. We treated our patient with thyroidectomy and subsequent intensified radiotherapy. Six months after treatment our patient is doing well and there is no sign of local reoccurrence. Our work-up is described, including the differentiation from metastatic disease. The origin of squamous cell carcinoma in the thyroid is uncertain; we discuss some theoretical considerations. We conclude that after excluding metastatic disease, thyroidectomy combined with radiotherapy is the treatment of choice.

Renal abnormalities in a family with Alagille syndrome.

Alagille syndrome is largely unknown to the general internist because the diagnosis is usually made by a paediatrician. Nevertheless, it is important to be aware of this syndrome because it sometimes manifests later in life with a great variability in clinical presentation and important consequences for the individual patient. We therefore discuss this syndrome using a patient with the usual characteristics of this syndrome.

Hepatocyte nuclear factor (HNF)1A and HNF4A substitution occurring simultaneously in a family with maturity-onset diabetes of the young.

INTRODUCTION: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by an early age at onset, autosomal dominant inheritance and a primary defect in the function of the B-cells of the pancreas. We report a family with two members carrying a substitution in both the hepatocyte nuclear factor (HNF)1A and HNF4A gene simultaneously. CASE REPORT: A 39-year-old man was referred because of mild diabetic retinopathy. Because of a dominant presentation of diabetes in his family, genetic testing was performed. Sequence analysis of the genes involved in MODY-1-3 revealed the presence of an amino acid substitution in the HNF1A as well as the HNF4A gene. Both substitutions were also detected in his mother. The HNF1A substitution has been described previously as pathogenic, whereas the HNF4A substitution had not been found previously. The HNF4A substitution was located in a conserved region of the protein and, additionally, the proband and his mother had high birthweights and low triglyceride levels, both of which are associated with pathogenic HNF4A substitutions. CONCLUSIONS: To our knowledge this is the first reported family carrying both a substitution of HNF1A and HNF4A gene simultaneously. The exact contribution of each substitution to the phenotype of our subjects remains to be further elucidated, however, given the high birthweights and the low triglyceride levels in those with both substitutions, it is reasonable that the HNF4A substitution is pathogenic.

[Schizophrenia and antipsychotics associated with the metabolic syndrome. An overview]. / Schizofrenie en antipsychotica: samenhang met het metabool syndroom.

BACKGROUND: Cardiovascular morbidity and mortality are higher in patients with schizophrenia than in the general population because the metabolic side-effects of antipsychotics and schizophrenia increase the risk of cardiovascular disease (cvd) and diabetes mellitus type 2 (DM2). The metabolic syndrome is defined in order to discover which patients have a high risk of developing cvd and DM2. AIM: To survey the current knowledge about the relationship between schizophrenia and the metabolic syndrome, the influence of the use of antipsychotics on the development of the metabolic syndrome, and the possible differences in the effects that first and second generation antipsychotics have on the syndrome. METHOD: The PubMed and Medscape databases were searched for relevant articles published between 2000 and July 2008. results Schizophrenia and the use of antipsychotics increase the prevalence of abdominal obesity, dyslipidemia and DM2 (i.e. the metabole syndrome). Second generation antipsychotics tend to cause a marked increase in the prevalence of abdominal obesity and dyslipidemia, whereas first generation antipsychotics hardly have any of these effects. Both first and second generation antipsychotics increase the risk of DM2. CONCLUSION: The metabolic syndrome has a significant effect on the morbidity and mortality of patients with schizophrenia because it increases the risk they will develop cvd and DM2. The risk increases still further if patients are taking antipsychotics. The risk of cvd can be decreased if patients with schizophrenia are screened in time and are monitored regularly.

Psoas abscess: report of a series and review of the literature.

We describe a series of twelve patients with a psoas abscess seen in a three-year period in a university hospital and a large teaching hospital in the Netherlands. In our series, five of the 12 patients had a primary psoas abscess. The predisposing conditions were intravenous drug use, diabetes mellitus, prostate carcinoma and haematoma in the psoas muscle in a patient with haemophilia A. Seven of the 12 patients had a secondary psoas abscess. Five cases were due to vertebral osteomyelitis including two cases of tuberculosis. In the other two cases it was due to colitis and urinary tract infection. It is remarkable that in our series there was only one patient with a psoas abscess secondary to a disease of the digestive tract, while this is the most common cause of a secondary psoas abscess in the literature. There were two cases of tuberculosis which is an emerging disease again.

[Empty sella syndrome as the cause of panhypopituitarism]. / Het 'empty sella'-syndroom als oorzaak van panhypopituïtarisme.

In two patients, men aged 78 and 42 years respectively, an empty-sella syndrome was found. The first patient presented with chronic fatigue, in the second the empty sella was the late result of prior neurosurgery followed by external irradiation. Both suffered from panhypopituitarism. In both cases the diagnosis was confirmed following laboratory tests and MRI. Hormone-replacement therapy was found to provide adequate treatment. The course of the empty-sella syndrome is usually benign and with adequate hormone-replacement therapy a good quality of life is maintained.