Childhood atopic disorders in relation to placental changes-A systematic review and meta-analysis.

Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS-I tool. The results were pooled both in a narrative way and by a meta-analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm-born children was associated with asthma-related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22-4.75)). In term-born children, a large placenta (≥750 g) increased the risk of being prescribed anti-asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term-born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms.

Cutibacterium avidum: A Potent and Underestimated Pathogen in Prosthetic Hip Joint Infections.

Cutibacterium avidum has recently been reported as a rare cause of prosthetic joint infections (PJIs), contrary to Cutibacterium acnes, which is well established as a cause of PJIs, especially in shoulder arthroplasties. Two specific risk factors for PJI due to C. avidum have been reported: obesity and the skin incision approach. Here, we report four cases of hip PJIs caused by C. avidum admitted over a 30-month period at a single center. Whole-genome sequencing revealed that the four C. avidum strains were all individual strains and did not originate from a common source, such as an outbreak. Antibiotic susceptibility tests showed that the isolates were fully susceptible, and none carried known antibiotic resistance genes. In conclusion, the occurrence of four cases of PJI caused by C. avidum over a limited time at a single center may indicate that this pathogen is underestimated and is either emerging or more common than previously recognized. The patients presented overt signs of infection during surgery, indicating that C. avidum is a virulent pathogen. None of the previously reported risk factors for C. avidum PJI applied to these patients as only one was obese and none were operated on using a direct anterior skin incision approach.

Adaptation of a guided low-intensity behavioral activation intervention for people with dementia in Sweden: a qualitative study exploring the needs and preferences of key stakeholders.

BACKGROUND: Despite depression being prevalent in people with dementia, contributing to negative health outcomes and placing increased burden on individuals and family members, access to psychological interventions is limited. A potential solution is guided low-intensity behavioral activation, supported by informal caregivers and guided by healthcare professionals. However, it is necessary to adapt interventions to meet the needs and preferences of key stakeholders to enhance acceptability and relevance. Study objectives were to: (1) explore needs and preferences concerning the content and delivery model of the guided low-intensity behavioral activation intervention; and (2) adapt the intervention to ensure cultural appropriateness, relevancy, and acceptability to people with dementia and their caregivers in Sweden. METHODS: Semi-structured interviews and focus group discussions were conducted with key stakeholders, including healthcare professionals (n = 18), community stakeholders (n = 7), people with dementia (n = 8), and informal caregivers (n = 19). A draft of the written low-intensity behavioral activation intervention and a description of the proposed intervention delivery model were provided to participants. Open-ended questions explored the perceived relevance of the intervention, alongside needs and preferences concerning content and delivery. A manifest content analysis approach was adopted. RESULTS: Content analysis resulted in three categories: Content, Delivery procedures, and Illness trajectory. Results highlighted a need to consider the intervention Content via increased cultural adaptation to the Swedish context, and increasing the inclusiveness of intervention content. Delivery procedures were identified as needing to be flexible given the unpredictable nature of caring for people with dementia, with the provision of additional guidance to informal caregivers supporting the intervention. Illness trajectory was viewed as essential to consider, with the intervention regarded as suitable for those early in the dementia trajectory, alongside a need to reduce workbook text to minimize burden given dementia symptomology. CONCLUSIONS: The intervention and proposed delivery model were generally well received by all stakeholders. We were able to identify key adaptations to enhance cultural appropriateness, relevancy, and acceptability for a currently neglected population. Results will inform a feasibility study to explore the feasibility and acceptability of the intervention and study procedures to inform the design of a future superiority randomized controlled trial. TRIAL REGISTRATION/PROTOCOL: Not applicable.

Periprosthetic joint infection after total hip arthroplasty induces histological degeneration of the gluteus medius tendon.

Aims: A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient's quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods: A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results: Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion: More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons.

Defective peripheral B cell selection in common variable immune deficiency patients with autoimmune manifestations.

Common variable immune deficiency (CVID) is a heterogeneous disorder characterized by recurrent infections, low levels of serum immunoglobulins, and impaired vaccine responses. Autoimmune manifestations are common, but B cell central and peripheral selection mechanisms in CVID are incompletely understood. Here, we find that receptor editing, a measure of central tolerance, is increased in transitional B cells from CVID patients and that these cells have a higher immunoglobulin κ:λ ratio in CVID patients with autoimmune manifestations than in those with infection only. Contrariwise, the selection pressure in the germinal center on CD27bright memory B cells is decreased in CVID patients with autoimmune manifestations. Finally, functionally, T cell-dependent activation showed that naive B cells in CVID patients are badly equipped for activation and induction of mismatch repair genes. We conclude that central tolerance is functional whereas peripheral selection is defective in CVID patients with autoimmune manifestations, which could underpin the development of autoimmunity.

Placental Changes and Neuropsychological Development in Children-A Systematic Review.

Placental dysfunction may increase the offspring's later-life disease risk. The objective of this systematic review was to describe associations between pathological placental changes and neuropsychological outcomes in children after the neonatal period. The inclusion criteria were human studies; original research; direct placental variables; neuropsychological outcomes; and analysis between their associations. The exclusion criterion was the offspring's age-0-28 days or >19 years. The MEDLINE and EMBASE databases were last searched in May 2022. We utilized the ROBINS-I for the risk of bias assessment and performed a narrative synthesis. In total, 3252 studies were identified, out of which 16 were included (i.e., a total of 15,862 participants). Half of the studies were performed on children with neonatal complications, and 75% of the studies reported an association between a placental change and an outcome; however, following the completion of the funnel plots, a risk of publication bias was indicated. The largest study described a small association between placental size and a risk of psychiatric symptoms in boys only. Inconsistency between the studies limited the evidence in this review. In general, no strong evidence was found for an association between pathological placental changes and childhood neuropsychological outcomes after the neonatal period. However, the association between placental size and mental health in boys indicates a placental sexual dimorphism, thereby suggesting an increased vulnerability for male fetuses.

Milk fatty acids as indicators of delayed commencement of luteal activity in dairy cows in early lactation.

Excessive mobilization of adipose reserves due to severe negative energy balance in early lactation may be detrimental to dairy cow fertility at individual and herd level. Reproductive efficiency is one of the main factors influencing herd profitability and a strategy for early detection and management of cows with delayed resumption of cyclicity will result higher conception rate, decreased proportion of cows with extended lactation, fewer inseminations per conception and lower culling rates due to reproductive disorders. Using two groups of dairy cows (Holstein n = 37, Swedish Red breed [SRB] n = 49), we investigated potential differences between cows with different commencement of luteal activity (CLA) and the feasibility of using milk fatty acids (MFAs) as predictors of delayed CLA. Milk samples for progesterone analysis were collected twice weekly during the first six weeks in milk. The concentrations of the MFAs C14:0, C16:0, C18:0 and C18:1 cis-9 in milk (g/100 g milk) and in milk fat (g/100 g fat) were analysed by Fourier transform infrared spectroscopy and individual MFA profiles were calculated by weeks in milk. Commencement of luteal activity was defined as the first day with milk progesterone concentrations >3 ng/ml at two successive measurements. The study population was categorized as early (n = 42) or late (n = 44) CLA, using the median value of 21 DIM as the cut-off. Analysis of the data revealed that CLA was correlated with the proportion of some specific MFAs, where cows with delayed CLA had lower IGF-1 (92.9 ± 7.9 vs. 114.1 ± 7.9 ng/ml; p = .05) and C14:0 levels (10.4 ± 0.2 vs. 11.5 ± 0.2 g/100 fat; p < .01) and higher C18:0 (9.6 ± 0.2 vs. 8.9 ± 0.6 g/100 fat; p < .01) and C18:1 cis-9 levels (24.9 ± 0.4 vs. 23.5 ± 0.4 g/100 fat; p < .05). Delayed CLA (mean 34 days) was predictable for approximately 80% of cows based on C18:0 or C18:1 cis-9 concentrations in week 2 postpartum. Overall, MFAs (C18:0 and C18:1 cis-9) as biomarkers were better indicators than beta-hydroxybutyrate or non-esterified fatty acids in early detection of cows with delayed or normal CLA. The MFA concentrations in milk samples from cows in early lactation can thus be used as a non-invasive method to identify cows at risk of delayed CLA, acting as potential biomarkers for future reproductive performance.

Group B streptococcus - a pathogen not restricted to neonates.

Objectives: This was a retropective study of invasive group B streptococcal (GBS) infections isolated from blood, cerebrospinal fluid (CSF), synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid and corpus vitreum in a defined region in southwest Sweden over a 14-year period. Design: Information on all invasive GBS infections was obtained from all four bacteriological laboratories in the region, with data obtained from individual patient records. Results: GBS was isolated from normally sterile body fluids in 1244 samples (579 from females and 665 from males) from 1101 patients. Of these patients, 196 were neonates. The incidence in neonates (0-27 days) was 7.3 per 100 000 live births per year, but there was a significant decrease from 2012 when risk-factor-based intrapartum antibibiotic prophylaxis was implemented. The great majority of neonatal infections were very early-onset infections. The incidence rates in children (28 days to 17 years), adults (18-64 years) and elderly patients (≥ 65 years) were 1.3, 3.6, and 12.9 per 100 000 per year, respectively. The majority of children and adults had severe underlying diseases, but severe infections were also seen in individuals with no risk factors. Conclusions: GBS is an important pathogen in all age groups. Intrapartum antibiotic prophylaxis significantly decreases very early-onset infections.

Full-lactation performance of multiparous dairy cows with differing residual feed intake.

Residual feed intake (RFI) is an efficiency trait underpinning profitability and environmental sustainability in dairy production. This study compared performance during a complete lactation of 36 multiparous dairy cows divided into three equal-sized groups with high (HRFI), intermediate (IRFI) or low RFI (LRFI). Residual feed intake was determined by two different equations. Residual feed intake according to the NorFor system was calculated as (RFINorFor) = (NEintake)-(NEmaintenance + NEgestation + NEmilk-NEmobilisation + NEdeposition). Residual feed intake according to the USA National Research Council (NRC) (RFINRC) was calculated as: RFI = DMI - predicted DMI where predicteds DMI = [(0.372× ECM)+(0.0968×BW0.75)]×(1-e-0.192×(DIM/7+3.67)). Cows in the HRFINorFor group showed higher daily CH4 production, CH4/ECM and CH4 yield (g/kg DMI) than IRFINorFor and LRFINorFor cows. Cows characterized by high efficiency (LRFINorFor) according to the NorFor system had lower body weight. Dry matter intake and apparent dry matter digestibility were not affected by efficiency group but milk yield was lower in the low efficiency, HRFINorFor, group. Cows characterized by high efficiency according to the NRC system (LRFINRC) had lower dry matter intake while yield of CH4 was higher. Daily CH4 production and CH4 g/kg ECM did not differ between RFINRC groups. Dairy cows characterized by high efficiency (both LRFINorFor and LRFINRC cows) over a complete lactation mobilized more of their body reserves in early lactation as well as during the complete lactation. The results also indicated great phenotypic variation in RFI between different stages the lactation.

Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden.

BACKGROUND: The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction. METHODS: Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher's exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test. RESULTS: With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis. CONCLUSIONS: Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Periprosthetic hip infections in a Swedish regional hospital between 2012 and 2018: is there a relationship between Cutibacterium acnes infections and uncemented prostheses?

The purpose of this study was to evaluate patients requiring in-patient care due to a periprosthetic joint infection (PJI), with respect to bacterial agents, surgical treatment, antibiotics, and outcome. We retrospectively identified all infected total hip arthroplasties (THAs) in a Swedish regional hospital during a 7-year period (2012-2018) and reviewed medical records and microbiological data. A total of 89 infected THAs in 87 patients were identified. Standardized treatment with debridement with retention of the implant and antibiotics (DAIR) was initially performed in 53 cases (60 %), one or two stage revisions in 33 cases (37 %), and an immediate Girdlestone in 3 cases (3 %). Infection eradication was seen in 77 PJIs (87 %) in addition to six patients (7 %) ending up with a permanent but uninfected Girdlestone. All six patients with manifest failures were infected with Staphylococcus aureus, two of which were also polymicrobial. Cutibacterium acnes was found in 18 of 89 patients (16 %) distributed in 15 uncemented implants but only in 3 hybrids and cemented arthroplasties, while remaining pathogens were equally distributed in uncemented THAs ( n = 31 ) and THAs with at least one cemented component ( n = 40 ; p = 0.003 ). Eradication was achieved in all 18 patients when Cutibacterium acnes was the only culture ( n = 14 ) or clearly dominant among positive cultures ( n = 4 ). DAIR was successful in selected postoperative infections up to 6 months after hip replacement. Cutibacterium acnes infections in hip arthroplasty may be underdiagnosed. Cemented components in THAs seem to protect from colonization with Cutibacterium acnes.

Genetic parameters of forage dry matter intake and milk produced from forage in Swedish Red and Holstein dairy cows.

High-yielding dairy cows are often fed high proportions of cereal grain and pulses. For several reasons, it would be desirable to replace these feed sources with forage, which is not suitable for human consumption. Feeding large amounts of forage to dairy cows could also make dairy production more publicly acceptable in the future. In this study, we estimated genetic parameters for total dry matter intake (DMI), DMI from forage (DMIFor), energy-corrected milk (ECM), and ECM produced from forage (ECMFor). A total of 1,177 lactations from 575 cows of Swedish Red (SR) and Holstein (HOL) dairy breeds were included in the study. Mixed linear animal random regression models were used, with fixed effect of calving season and lactation week nested within parity 1 and 2+, fixed effect of calving year, and random regression coefficients for breeding value (up to linear) and permanent environmental effect (up to quadratic) of the cow. Heritability for DMI and DMIFor was generally higher for HOL than for SR in all-parity data and in later parities; however, the opposite was true for first parity. Heritability for DMI and DMIFor during the first 8 wk averaged 0.11 and 0.15, respectively, in all-parity data for the 2 breeds. Corresponding values for ECMFor and ECM were 0.21 and 0.29, respectively. In first parity, values were 0.32, 0.36, 0.28, and 0.51, respectively. The genetic correlation between DMI and DMIFor was high, above 0.83, and fairly constant across the lactation. The genetic correlation between ECMFor and ECM was close to unity in the later part of lactation for both breeds, but was around 0.8 in the early lactation for both breeds; it decreased for HOL to 0.54 in wk 17. The genetic correlations between DMI and ECMFor and between DMIFor and ECMFor were low and negative for HOL (absolute value ∼0.2-0.3), but changed for SR from weakly positive in early lactation to negative values and back to positive toward the end of lactation. For most traits, the correlation between wk 1 and wk 8 into the lactation was very high; the lowest value was for DMI in HOL at 0.81. The genetic correlation between parities was rather high in the first part of the lactation. During the first 8 wk, the correlation was lower for HOL than for SR, except for ECM. We found that DMIFor and ECMFor showed reasonably large heritability, and future work should explore the possibility of genomic evaluations.

Whole-lactation feed intake, milk yield, and energy balance of Holstein and Swedish Red dairy cows fed grass-clover silage and 2 levels of byproduct-based concentrate.

Ruminants can produce meat and milk from fibrous feed and byproducts not suitable for human consumption. However, high-yielding dairy cows are generally fed a high proportion of cereal grain and pulses, which could be consumed directly by humans. If high production of dairy cows could be maintained with ingredients of low human interest, the sustainability of dairy production would improve. In the present study, 37 multiparous [Holstein (n = 13) and Swedish Red (n = 24)] dairy cows were followed over a whole lactation. A low-concentrate diet of up to 6 kg concentrate per day (6kgConc) was fed to 27 cows, whereas 10 cows were fed a high-concentrate diet of up to 12 kg concentrate per day (12kgConc). The concentrate was mainly based on byproducts (sugar beet pulp, wheat bran, rapeseed meal, distiller's grain). Grass-clover silage of high digestibility was offered ad libitum. Over the whole lactation, cows on the 6kgConc diet had lower dry matter intake and higher forage intake than cows on the 12kgConc diet. Milk yield and energy balance were not influenced by dietary treatment. However, the cows on the 6kgConc diet numerically produced 2.4 kg less energy-corrected milk than cows on 12kgConc diet. The study lacked the statistical power to identify treatment effects on daily yield below 2.8 kg of milk due to low number of animals per treatment. Feed efficiency (as energy-corrected milk yield/dry matter intake or residual feed intake), body weight change, body condition change, milk fatty acid concentration in total milk fatty acids, plasma nonesterified fatty acids, glucose, ß-hydroxybutyrate, and fertility measurements were not affected by diet, supporting the energy balance results. However, higher plasma concentrations of insulin-like growth factor-1 and insulin were observed in cows fed the 12kgConc diet. These findings show that cows can adapt to a high-forage diet virtually without human-grade ingredients, without compromising feed efficiency or energy balance, thereby contributing to sustainable food production.

Effects of replacing wheat starch with glycerol on methane emissions, milk production, and feed efficiency in dairy cows fed grass silage-based diets.

To lower the effect of climate change from cattle production, we should aim at decreasing their enteric methane emissions per kilogram of milk or meat. Glycerol may be absorbed through the rumen epithelium and would consequently be less available to microbes in the rumen. Glycerol could thus supply dairy cows with energy for milk production without contributing much to methane production. This study evaluated the effect of replacing wheat starch with glycerol on milk production, feed intake, and methane emissions. Twenty-two Swedish Red cows in mid lactation were used in a switch-back, change-over experiment with 3 periods of 21 d. The 2 dietary treatments consisted of a total mixed ration based on (g/kg of dry matter) grass silage (605), rapeseed meal (120), and barley (70) and either wheat starch or refined glycerol (200) fed ad libitum. The glycerol diet resulted in higher dry matter intake (21.6 vs. 20.1 kg/d) and methane emissions (482 vs. 423 g/d) compared with the diet containing wheat starch, whereas no difference was found in energy-corrected milk yield (28.4 vs. 29.7 kg/d). These results indicate that when glycerol is mixed with the feed, it is available to rumen microbes to a larger extent than initially assumed. Compared with wheat starch, adding refined glycerol (200 g/kg of dry matter) to the feed of dairy cows does not seem to have the potential to decrease enteric methane emissions.

Replacing human-edible feed ingredients with by-products increases net food production efficiency in dairy cows.

Global demand for food is increasing, and use of large amounts of potentially human-edible feedstuffs for dairy cows is an important concern. The present study examined whether feeding a by-product-based concentrate combined with high-quality grass silage to high-producing dairy cows affected feed intake and milk production compared with a conventional diet, as well as the effect on efficiency of human food production. In a changeover experiment with four 21-d periods, 24 dairy cows in mid-lactation were offered 9.6 kg of dry matter per day with 1 of 4 concentrates and high-quality grass silage ad libitum. The control concentrate was based on cereal grain (wheat, oat, and barley) and soybean meal, whereas the 3 by-product-based concentrates contained sugar beet pulp in combination with mainly heat-treated rapeseed meal, distillers grain, or a mixture of both. All diets were formulated to be isoenergetic and isonitrogenous. The cows had 10-fold higher starch intake when fed the control diet than when fed the by-product-based concentrates. Silage intake (13 kg of dry matter/d) and milk production (33 kg of energy-corrected milk/d) were not affected by the change in diet. Therefore, replacing cereals and soybean meal with human-inedible by-products in a high-quality forage diet to dairy cows increased net food protein production substantially without lowering milk production.

No differences in central corneal thickness between open-angle and pseudoexfoliation glaucoma patients.

INTRODUCTION: Measurements of intraocular pressure (IOP) with Goldmann applanation tonometry are affected by central corneal thickness (CCT), as thinner corneas underestimate and thicker corneas overestimate the true IOP value. The literature is controversial regarding CCT values in patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (XFG). The aim of this study was to evaluate CCT in patients with XFG and POAG. METHODS: CCT was evaluated with optical coherence tomography (OCT). All participants who were previously diagnosed with either POAG or XFG underwent ophthalmological examinations. Contact lens users and patients with corneal diseases were excluded. RESULTS: Totally, 145 patients were enrolled in this study. The mean CCT was 535±30.4 µm in patients with POAG and was 536±33.7 µm in patients with XFG. The result was not statistically significant (P=0.98). The mean age for all participants was 73.8±7.7 years. The study included totally 61 women and 84 men. The two groups were similar in their demographic data, and mean deviation was the only parameter that differed statistically when comparing POAG with XFG (P=0.02). CONCLUSION: Our data indicate that patients with XFG do not have thinner corneas than those with POAG, and therefore, CCT can not explain why they progress differently.

Poor Correlation between Pneumococcal IgG and IgM Titers and Opsonophagocytic Activity in Vaccinated Patients with Multiple Myeloma and Waldenstrom's Macroglobulinemia.

Patients with multiple myeloma and other B cell disorders respond poorly to pneumococcal vaccination. Vaccine responsiveness is commonly determined by measuring pneumococcal serotype-specific antibodies by enzyme-linked immunosorbent assay (ELISA), by a functional opsonophagocytosis assay (OPA), or by both assays. We compared the two methods in vaccinated elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance (MGUS). Postvaccination sera from 45 patients (n= 15 from each patient group) and 15 control subjects were analyzed by multiplexed OPA for pneumococcal serotypes 4, 6B, 14, and 23F, and the results were compared to IgG and IgM antibody titers measured by ELISA. While there were significant correlations between pneumococcal OPA and IgG titers for all serotypes among the control subjects (correlation coefficients [r] between 0.51 and 0.85), no significant correlations were seen for any of the investigated serotypes in the myeloma group (r= -0.18 to 0.21) or in the group with Waldenstrom's macroglobulinemia (borderline significant correlations for 2 of 4 serotypes). The MGUS group resembled the control group by having good agreement between the two test methods for 3 of 4 serotypes (r= 0.53 to 0.80). Pneumococcal postvaccination IgM titers were very low in the myeloma patients compared to the other groups and did not correlate with the OPA results. To summarize, our data indicate that ELISA measurements may overestimate antipneumococcal immunity in elderly subjects with B cell malignancies and that a functional antibody test should be used specifically for myeloma and Waldenstrom's macroglobulinemia patients.

Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance.

Whereas patients with multiple myeloma (MM) have a well-documented susceptibility to infections, this has been less studied in other B-cell disorders, such as Waldenstrom's macroglobulinemia (WM) and monoclonal gammopathy of undetermined significance (MGUS). We investigated the humoral immunity to 24 different pathogens in elderly patients with MM (n = 25), WM (n = 16), and MGUS (n = 18) and in age-matched controls (n = 20). Antibody titers against pneumococci, staphylococcal alpha-toxin, tetanus and diphtheria toxoids, and varicella, mumps, and rubella viruses were most depressed in MM patients, next to lowest in WM and MGUS patients, and highest in the controls. In contrast, levels of antibodies specific for staphylococcal teichoic acid, Moraxella catarrhalis, candida, aspergillus, and measles virus were similarly decreased in MM and MGUS patients. Comparable titers in all study groups were seen against Haemophilus influenzae type b (Hib), borrelia, toxoplasma, and members of the herpesvirus family. Finally, a uniform lack of antibodies was noted against Streptococcus pyogenes, salmonella, yersinia, brucella, francisella, and herpes simplex virus type 2. To conclude, although MM patients displayed the most depressed humoral immunity, significantly decreased antibody levels were also evident in patients with WM and MGUS, particularly against Staphylococcus aureus, pneumococci, and varicella. Conversely, immunity was retained for Hib and certain herpesviruses in all study groups.