Cesarean section - short term maternal complications related to the mode of delivery

Cesarean section (CS) is the most common major surgery performed on women worldwide. CS can save the life of the mother or the fetus, but is associated with the typical complications of any major surgery: hemorrhage, infection, venous thromboembolism and complications of anesthesia, sometimes leading to maternal death. Recently there have been several reports from well resourced countries on increased severe maternal morbidity and even mortality. Increased rates of CS, obesity and older mothers may explain this rise. The aim of this thesis is to study the rates and risk factors of short term maternal complications associated with CS. Also, we compared maternal morbidity by mode of delivery and over time. The complication rates were assessed in a prospective study involving 2496 CS performed in the 12 largest delivery units in Finland in 2005. The rates of severe complications were studied by mode of delivery in a register-based study comparing national cohorts in 1997 and 2002. The impact of several risk factors on severe maternal morbidity by mode of delivery was studied in a register-based study of all singleton deliveries in 2007-2011. In the prospective study, 27% of the women who underwent CS had one or more intraoperative or postoperative complications during their hospital stay, and 10% had a severe complication. In the register-based study the incidence of life-threatening maternal complications was 7.6 in 1000 deliveries. The incidence was lowest for vaginal delivery (VD), followed by instrumental VD and elective CS, and highest in emergency CS. An attempt of VD, including the risks associated with emergency CS, seems to be the safest mode of delivery, even for most high-risk women.

Complications of surgical treatment of cervical carcinoma

A total of 302 patients with stage Ib and IIa cervical carcinoma were submitted to radical hysterectomy and lymphadenectomy during the period from 1980 to 1994. The morbidity rate was 37.5% and the mortality rate 0.6%. The most common intraoperative complications were injuries to the great pelvic vessels and the most frequent postoperative complications involved the urinary tract. The leading causes of morbidity were urinary infection (20.8%), bladder dysfunction (9.2%) and ureteral fistulas (2.9%). Although the rate of complications was high, morbidity has been decreasing over the last five years. Thus, radical hysterectomy continues to be one of the methods for the treatment of early cervical carcinoma that presents an acceptable 5-year survival rate.

Factors associated with the development of renal complications of diabetes mellitus in São Paulo city

The incidence of diabetic end-stage renal failure (ESRF) varies worldwide and risk factors have been demonstrated in several populations. The objective of the present study was to identify possible factors associated with the risk of development of ESRF in patients with diabetes mellitus (DM). Two groups of diabetic subjects were included in a case-control study: 1) one group was submitted to renal replacement therapies, attending dialysis centers in São Paulo city and 2) the same number of controls without clinical nephropathy (two negative dipstick tests for urine protein), matched for duration of DM, were obtained from an outpatient clinic. A standardized questionnaire was used by a single investigator and additional data were obtained from the medical records of the patients. A total of 290 diabetic patients from 33 dialysis centers were identified, and 266 questionnaires were considered to contain reliable information. Male/female ratios were 1.13 for ESRF and 0.49 for the control group. A higher frequency of men was observed in the ESRF group when compared with controls (53 vs 33%, P<0.00001), although logistic regression analysis did not confirm an association of gender and diabetic nephropathy (DN). Similar proportions of non-white individuals were found for both groups. Patients with insulin-dependent diabetes mellitus (IDDM) were less common than patients with non-insulin-dependent diabetes mellitus (NIDDM), particularly in the control group (3.4 vs 26.3%, P<0.00001, for controls and ESRF patients, respectively); this type of DM was associated with a higher risk of ESRF than NIDDM, as determined by univariate analysis or logistic regression (OR = 4.1). Hypertension by the time of the DM diagnosis conferred a 1.4-fold higher risk of ESRF (P = 0.04), but no difference was observed concerning the presence of a family history. Association between smoking and alcohol habits and increased risk was observed (OR = 4.5 and 5.9, respectively, P<0.001). A 2.4-fold higher risk of ESRF was demonstrated in patients with multiple hospitalizations due to DM decompensation, which suggested poor metabolic control. Photocoagulation and neuropathy were found to be strongly associated with ESRF but not with macrovascular disease. Data collected in our country reinforce the higher risk attributable to IDDM and the association between hypertension and the progression of DN. Indirect evidence for an association with metabolic control is also suggested

Residual ß-cell function and microvascular complications in type 1 diabetic patients

To determine the influence of residual ß-cell function on retinopathy and microalbuminuria we measured basal C-peptide in 50 type 1 diabetic outpatients aged 24.96 ± 7.14 years, with a duration of diabetes of 9.1 ± 6.2 years. Forty-three patients (86%) with low C-peptide (<0.74 ng/ml) had longer duration of diabetes than 7 patients (14%) with high C-peptide (³0.74 ng/ml) (9 (2-34) vs 3 (1-10) years, P = 0.01) and a tendency to high glycated hemoglobin (HBA1) (8.8 (6-17.9) vs 7.7 (6.9-8.7)%, P = 0.08). Nine patients (18%) had microalbuminuria (two out of three overnight urine samples with an albumin excretion rate (AER) ³20 and <200 µg/min) and 13 (26%) had background retinopathy. No association was found between low C-peptide, microalbuminuria and retinopathy and no difference in basal C-peptide was observed between microalbuminuric and normoalbuminuric patients (0.4 ± 0.5 vs 0.19 ± 0.22 ng/ml, P = 0.61) and between patients with or without retinopathy (0.4 ± 0.6 vs 0.2 ± 0.3 ng/ml, P = 0.43). Multiple regression analysis showed that duration of diabetes (r = 0.30, r2 = 0.09, P = 0.031) followed by HBA1 (r = 0.41, r2 = 0.17, P = 0.01) influenced basal C-peptide, and this duration of diabetes was the only variable affecting AER (r = 0.40, r2 = 0.16, P = 0.004). In our sample of type 1 diabetic patients residual ß-cell function was not associated with microalbuminuria or retinopathy.

Cardiovascular complications and increased levels of circulating modified low density lipoprotein in HIV patients and patients with lipodystrophy

The introduction of highly active antiretroviral therapy (HAART) for patients infected with HIV has significantly prolonged the life expectancy and to some extent has restored a functional immune response. However, the premature introduction of HAART has led to a significant and alarming increase in cardiovascular complications, including myocardial infarction and the appearance of abnormal distribution of body fat seen as lipodystrophy. One key element in the development of ischemic coronary artery disease is the presence of circulating and tissue-fixed modified low density lipoprotein (mLDL) that contributes to the initiation and progression of arterial lesions and to the formation of foam cells. Even though not completely elucidated, the most likely mechanism involves mLDL in the inflammatory response and the induction of a specific immune response against mLDL. Circulating antibodies against mLDL can serve as an indirect marker of the presence of circulating and vessel-fixed mLDL. In the present study, we measured antibodies to mLDL and correlated them with immune status (i.e., number of CD4+ T cells) in 59 HIV patients and with the clinical manifestation of lipodystrophy in 10 patients. We observed a significant reduction in anti-mLDL antibody levels related both to lipodystrophy and to an immunocompromised state in HIV patients. We speculate that these antibodies may explain in part the rapid development of ischemic coronary artery disease in some patients.

The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease

Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

The role of K121Q ENPP1 polymorphism in diabetes mellitus and its complications

The aim of the present study was to analyze the frequency of K121Q polymorphism in the ENPP1 gene of Brazilian subjects according to ethnic origin and to determine its possible association with diabetes mellitus (DM) and/or diabetic complications. A cross-sectional study was conducted on 1027 type 2 DM patients and 240 anonymous blood donors (BD). Ethnicity was classified based on self-report of European and African descent. The Q allele frequency was increased in African descendant type 2 DM patients (KK = 25.9%, KQ = 48.2%, and QQ = 25.9%) and BD (KK = 22.0%, KQ = 53.8%, and QQ = 24.2%) compared to European descendant type 2 DM patients (KK = 62.7%, KQ = 33.3%, and QQ = 4.1%) and BD (KK = 61.0%, KQ = 35.6%, and QQ = 3.4%). However, there was no difference in genotype distribution or Q allele frequency between diabetic and non-diabetic subjects (European descendants: DM = 0.21 vs BD = 0.21, P = 0.966, and African descendants: DM = 0.50 vs BD = 0.51, P = 0.899). In addition, there were no differences in clinical, laboratory or insulin resistance indices among the three genotypes. The prevalence of DM complications was also similar. In conclusion, K121Q polymorphism is more common among Afro-Brazilian descendants regardless of glycemic status or insulin sensitivity indices. Likewise, insulin sensitivity and DM chronic complications appear not to be related to the polymorphism in this sample.

Vascular complications of black patients with type 2 diabetes mellitus in Southern Brazil

Ethnicity has been shown to be associated with micro- and macrovascular complications of diabetes in European and North American populations. We analyzed the contribution of ethnicity to the prevalence of micro- and macrovascular complications in Brazilian subjects with type 2 diabetes attending the national public health system. Data from 1810 subjects with type 2 diabetes (1512 whites and 298 blacks) were analyzed cross-sectionally. The rates of ischemic heart disease, peripheral vascular disease, stroke, distal sensory neuropathy, and diabetic retinopathy were assessed according to self-reported ethnicity using multiple logistic regression models. Compared to whites, black subjects [odds ratio = 1.72 (95%CI = 1.14-2.6)] were more likely to have ischemic heart disease when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, smoking habit, and serum creatinine. Blacks were also more likely to have end-stage renal disease [3.2 (1.7-6.0)] and proliferative diabetic retinopathy [1.9 (1.1-3.2)] compared to whites when data were adjusted for age, sex, fasting plasma glucose, HDL cholesterol, hypertension, and smoking habit. The rates of peripheral vascular disease, stroke and distal sensory neuropathy did not differ between groups. The higher rates of ischemic heart disease, end-stage renal disease and proliferative diabetic retinopathy in black rather than in white Brazilians were not explained by differences in conventional risk factors. Identifying which aspects of ethnicity confer a higher risk for these complications in black patients is crucial in order to understand why such differences exist and to develop more effective strategies to reduce the onset and progression of these complications.

The prevalence of chronic diabetic complications and metabolic syndrome is not associated with maternal type 2 diabetes

The maternal history of type 2 diabetes mellitus (DM) has been reported more frequently in patients with type 2 DM than paternal history. The aim of the present study was to determine if there was an association between maternal history of DM and the presence of chronic complications or metabolic syndrome (MetS) in patients with type 2 DM. A cross-sectional study was conducted with 1455 patients with type 2 DM. All outpatients with type 2 diabetes attending the endocrine clinics who fulfilled the eligibility criteria were included. Familial history of DM was determined with a questionnaire. Diabetic complications were assessed using standard procedures. The definition of MetS used was that of the World Health Organization and the National Cholesterol Education Program's Adult Treatment Panel III report criteria. Maternal history of DM was present in 469 (32.3%), absent in 713 (49.1%) and unknown in 273 patients (18.7%). Paternal history of DM was positive in 255 (17.6%), negative in 927 (63.8%) and unknown in 235 patients (16.1%). The frequency of microvascular chronic complications in patients with and without a positive maternal history of DM was similar: diabetic nephropathy (51.5 vs 52.5%), diabetic retinopathy (46.0 vs 41.7%), and diabetic sensory neuropathy (31.0 vs 37.1%). The prevalence of macrovascular chronic complications and MetS was also similar. Patients with type 2 DM were more likely to have a maternal than a paternal history of DM, although maternal history of DM was not associated with an increased prevalence of chronic complications or MetS.

Maternal serum progesterone, estradiol and estriol levels in successful dinoprostone-induced labor

Hormone-mediated quiescence involves the maintenance of a decreased inflammatory responsiveness. However, no study has investigated whether labor induction with prostanoids is associated with changes in the levels of maternal serum hormones. The objective of this study was to determine whether labor induction with dinoprostone is associated with changes in maternal serum progesterone, estradiol, and estriol levels. Blood samples were obtained from 81 pregnant women at term. Sixteen patients had vaginal birth after spontaneous labor, 12 required cesarean section after spontaneous labor and 16 underwent elective cesarean. Thirty-seven patients had labor induction with dinoprostone. Eligible patients received a vaginal insert of dinoprostone (10 mg) and were followed until delivery. Serum progesterone (P4), estradiol (E2) and estriol (E3) levels and changes in P4/E2, P4/E3 and E3/E2 ratios were monitored from admission to immediately before birth, and the association of these measures with the resulting clinical classification outcome (route of delivery and induction responsiveness) was assessed. Progesterone levels decreased from admission to birth in patients who underwent successful labor induction with dinoprostone [vaginal and cesarean birth after induced labor: 23% (P < 0.001) and 18% (P < 0.025) decrease, respectively], but not in those whose induction failed (6.4% decrease, P > 0.05). Estriol and estradiol levels, P4/E2, P4/E3 and E3/E2 ratios did not differ between groups. Successful dinoprostone-induced labor was associated with reduced maternal progesterone levels from induction to birth. While a causal relationship between progesterone decrease and effective dinoprostone-induced labor cannot be established, it is tempting to propose that dinoprostone may contribute to progesterone withdrawal and favor labor induction in humans.

Inclusion or Exclusion? Trade union strategies and Labor migration

Inclusion or Exclusion? Trade Union Strategies and Labor Migration This research identified and analyzed immigration-related strategies of the Finnish Construction Trade Union (FCTU) and the Service Union United (SUU); e.g. how the unions react to labor immigration, whether unions seek to include migrants in the unions, and what is migrants’ position in the unions. The two unions were chosen as the focus of the research because the workforce in the sectors they represent is migrant-dense. The study also analyzed the experiences that migrants who work in these sectors have with trade unions. The Estonian labor market situation –including the role of Estonian trade unions– was also examined as it has a considerable impact on the operating environment of the FCTU. The results of the study indicate that immigration is a contradictory issue for both unions. On the one hand, they strive to include migrants as trade union members and to defend migrants’ labor rights. On the other hand, they, together with their umbrella organization the Central Organisation of Finnish Trade Unions (SAK), seek to prevent labor immigration from outside the EU and EEA countries. They actively defend current labor immigration restrictions by drawing atten- tion to high unemployment figures and to the breaches of working conditions migrants encounter. In contrast, the employer organizations promote a more liberal state policy on labor immigration because they see it as a boost for business. Both the unions and the employer organizations ground their arguments on national interest. However, the position of the trade union movement is not uniform: unions belonging to the Confederation of Unions for Professionals and Managerial Staff in Finland (Akava) embrace more liberal labor immigration stances than the SAK. A key trade union strategy is to try to guarantee that migrants’ working condi- tions do not differ from those of the natives. The FCTU and the SUU inform migrants about Finnish collective agreements and trade union membership in the most common migrant languages. This is important for the unions because it is not in their interest that migrants’ working conditions are undercut. The interviewed migrants said that natives had more negotiating power with employers, which is often negatively portrayed in migrants’ working conditions. Migrants perceive that trade unions have an important role in protecting their working conditions. However, they stressed that migrants’ knowledge of unions is often very limited. The number of migrants in both two unions studied here is increasing. Espe- cially in the SUU, a considerable proportion of the new members are migrants. The FCTU is in a more challenging situation than the SUU because migrant construc- tion workers often work only for short periods in Finland and are consequently not interested in becoming union members. The unions’ strategies partly differ: the FCTU was the first Finnish trade union to establish a trade union branch/lo- cal for migrant members. The goal is to facilitate migrants’ inclusion in the union and to highlight the specific problems they face. The SUU, for its part, insists that such a special strategy would exclude migrants within the union organization. Despite the unions’ strategies, migrants are still underrepresented as union members and officials, which some of the interviewed migrants saw as a problem. Immigrants’ perception of trade unions was pragmatic: they had joined unions when membership yielded concrete benefits. In spite of the unions’ strategies, migrants –and temporary migrants– encoun- ter specific problems in terms of working conditions. Both unions demand more state intervention to protect migrants’ labor rights because overseeing working conditions consumes union resources. However, without the unions’ intervention, these problems would be more common than is currently the case. For instance, some of the interviewed migrants had received trade union assistance in claim- ing unpaid wages. The study demonstrated with the help of building on Walter Korpi’s power resources theory, that immigration is a power resource issue for the unions: suc- cessful immigration-related strategies strengthen unions –and vice versa. The research also showed how the unions’ operating environments constrain and enable their immigration-related strategies. This study has illuminated a previously ignored dimension: the immigrant- inclusive strategies of the Finnish trade unions. The research material consists of 78 qualitative interviews, observation in trade union events, and trade unions’ and employer organizations’ public state- ments.

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.

Bearing-spesific complications of total hip arthroplasty: characterization and treatment

Hip resurfacing arthroplasty (HRA) and large head metal-on-metal total arthroplasty (LDH MoM THA) gained popularity during the last decade. Adverse reaction to metal debris (ARMD) is a unique complication of metal bearings. ARMD is a complex reaction caused by metal debris from metal-on- metal bearing surfaces and from trunnion corrosion of modular junctions. We analyzed survivorship of 8059 LDH MoM THAs based on data of the Finnish Arthroplasty Register. We found relatively high short-term survivorship for some LDH MoM THAs, but there were remarkable differences between the devices studied. After some alarming reports of failing MoM THAs, we studied the first 80 patients who had received a ReCap-M2a-Magnum implant at our institution and evaluated the prevalence of ARMD. We found a high prevalence of pseudotumors, and, because of this, we discontinued the use of MoM bearings and followed up all patients with a MoM THA. Bone loss due infection, osteolysis or fracture poses a great challenge for reconstructive and fracture surgery. Onlay allografting for both revision and fracture surgery provides mechanical stability and increases bone stock. Bone loss and implant stability must be assessed preoperatively and adequately classified; this provides guidelines for the operative treatment of periprosthetic fractures and revision THA. In our studies on structural allografts union rates were high, although the rates of infections and dislocations were marked. In summary, early results of the use of LDH MoM devices were encouraging. However, the survival of the LDH MoMs varied. The prevalence of adverse reaction to metal debris was high after application of the ReCap-Magnum THA. New implants should be introduced carefully and under close surveillance by University clinics and arthroplasty registers.