Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology that underlies this observation is poorly understood. We ...previously reported that "atypical" memory B cells are increased in children and adults exposed to intense Pf transmission in Mali, similar to what has been observed in individuals infected with HIV. In this study we examined B cell subsets of Pf -infected adults in Peru and Mali to determine if Pf transmission intensity correlates with atypical memory B cell expansion.
In this cross-sectional study venous blood was collected from adults in areas of zero (U.S., n = 10), low (Peru, n = 18) and high (Mali, n = 12) Pf transmission. Adults in Peru and Mali were infected with Pf at the time of blood collection. Thawed lymphocytes were analyzed by flow cytometry to quantify B cell subsets, including atypical memory B cells, defined by the cell surface markers CD19(+) CD20(+) CD21(-) CD27(-) CD10(-). In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% 95% CI: 3.61-7.28; U.S. mean: 1.4% 95% CI: 0.92-1.81; p<0.0001) but lower than Malian adults (Mali mean 13.1% 95% CI: 10.68-15.57; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% 95% CI: 4.09-9.11; no prior episodes mean: 3.1% 95% CI: 1.52-4.73; p = 0.028).
Compared to Pf-naive controls, atypical memory B cells were increased in Peruvian adults exposed to low Pf transmission, and further increased in Malian adults exposed to intense Pf transmission. Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:Restorative proctocolectomy is the procedure of choice in patients with ulcerative colitis refractory to medical therapy. Prepouch ileitis is characterized by mucosal inflammation ...immediately proximal to the pouch. Prepouch ileitis is uncommon, and long-term follow-up data are lacking.
OBJECTIVE:The aim of this study is to report the long-term outcomes of prepouch ileitis.
DESIGN:We followed up a cohort of patients with prepouch ileitis that was originally described in 2009. Patients were followed up until the last recorded clinic attendance or at the point of pouch failure. Follow-up data collected included stool frequency, endoscopic findings, treatment, and overall pouch function.
SETTING:We accessed a prospectively maintained database at our institution between January 2009 and January 2017.
PATIENTS:Three of the 34 patients originally described in 2009 were lost to follow-up; we reanalyzed data on the remaining 31.
MAIN OUTCOME MEASURE:The rate of pouch failure was defined as the need for ileostomy or pouch revision.
RESULTS:All 31 patients had coexisting pouchitis at index diagnosis of prepouch ileitis. The median length of follow-up from the index pouchoscopy was 98 (range, 27–143) months. Seven (23%) patients who had an index pouchoscopy with prepouch ileitis went on to pouch failure, which is significantly higher than expected (p = 0.03). Five (71%) of these patients had chronic pouchitis, and 2 (29%) had small-bowel obstruction due to prepouch stricture. Two patients had evidence that would support possible Crohn’s disease at long-term follow-up.
LIMITATIONS:This was a retrospective analysis. Because of the nature of the study, there was some missing information that may have influenced the results. Our study is further limited by small patient numbers.
CONCLUSIONS:Prepouch ileitis is associated with a significantly increased risk of pouch failure compared with the overall reported literature for restorative proctocolectomy. Prepouch ileitis does not appear to be strongly predictive of Crohn’s disease at long-term follow-up. See Video Abstract at http://links.lww.com/DCR/A480.
Abstract
Background
Advancements in treatment and supportive care have led to improved survival for adolescents and young adults (AYAs) with cancer; however, a subset of those diagnosed remain at ...risk for early death (within 2 months of diagnosis). Factors that place AYAs at increased risk of early death have not been well studied.
Methods
The Surveillance, Epidemiology, and End Results registry was used to assess risk of early death in AYAs with hematologic malignancies, central nervous system tumors, and solid tumors. Associations between age at diagnosis, sex, race, ethnicity, socioeconomic status, insurance status, rurality, and early death were assessed.
Results
A total of 268 501 AYAs diagnosed between 2000 and 2016 were included. Early death percentage was highest in patients diagnosed with hematologic malignancies (3.1%, 95% confidence interval CI = 2.9% to 3.2%), followed by central nervous system tumors (2.5%, 95% CI = 2.3% to 2.8%), and solid tumors (1.0%, 95% CI = 0.9% to 1.0%). Age at diagnosis, race, ethnicity, lower socioeconomic status, and insurance status were associated with increased risk of early death in each of the cancer types. For AYAs with hematologic malignancies and solid tumors, risk of early death decreased statistically significantly over time.
Conclusions
A subset of AYAs with cancer remains at risk for early death. In addition to cancer type, sociodemographic factors also affect risk of early death. A better understanding of the interplay of factors related to cancer type, treatment, and health systems that place certain AYA subsets at higher risk for early death is needed to address these disparities and improve outcomes.
Aim
Total colectomy with ileorectal anastomosis (TC‐IRA) is a surgical option for patients with familial adenomatous polyposis (FAP). Regular endoscopic surveillance of the rectum is recommended to ...prevent rectal cancer. We aimed to document polyp progression in the rectum following TC‐IRA and evaluate the role of polypectomy during surveillance.
Method
Patients with FAP who underwent TC‐IRA between 1990 and 2017 were identified. Demographic, endoscopic and genetic data were retrieved. Cumulative rectal adenoma (polyp) counts were obtained, whilst accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing secondary proctectomy were evaluated.
Results
One hundred and ninety‐nine patients fulfilled our inclusion criteria, of which 44% were male. The median age at colectomy was 19 (range 11–70) years and median preoperative rectal polyp count was 7 (range 0–50). All patients had an APC pathogenic variant, of which 151 (79%) were 5' of the mutation cluster region (MCR), 19 (10%) in the MCR, six (3%) were 3' of the MCR and 15 (8%) had a gross deletion. After a median follow‐up of 8.6 (range1–27) years and a median of 11 (range 2–37) flexible sigmoidoscopies per patient, the median rate of polyp progression was 5.5 polyps/year (range 0–70.2). There was no evidence of polyp regression. Eight (4%) patients underwent secondary proctectomy for neoplasia, of which one (0.5%) had rectal adenocarcinoma. A total of 13,527 polyps were removed, a median of 35 polyps/patient (range 0–829). The rate of polyp progression was not significantly associated with genotypic or phenotypic factors.
Conclusion
Progression of rectal adenoma burden following TC‐IRA appears to be slow and dependent on the length of follow‐up. In the modern era of stringent endoscopic surveillance and therapeutic procedures such as cold snare polypectomy, the rate of secondary proctectomy and the risk of rectal cancer after TC‐IRA are very low. These findings are important when counselling patients with regard to the choice of surgery for FAP and implementing endoscopic surveillance.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Polyglutamine-induced neurodegeneration in transgenic mice carrying the spinocerebellar ataxia type 1 (SCA1) gene is modulated by subcellular distribution of ataxin-1 and by components of the protein ...folding/degradation machinery. Since phosphorylation is a prominent mechanism by which these processes are regulated, we examined phosphorylation of ataxin-1 and found that serine 776 (S776) was phosphorylated. Residue 776 appeared to affect cellular deposition of ataxin-182Q in that ataxin-182Q-A776 failed to form nuclear inclusions in tissue culture cells. The importance of S776 for polyglutamine-induced pathogenesis was examined by generating ataxin-182Q-A776 transgenic mice. These mice expressed ataxin-182Q-A776 within Purkinje cell nuclei, yet the ability of ataxin-182Q-A776 to induce disease was substantially reduced. These studies demonstrate that polyglutamine tract expansion and localization of ataxin-1 to the nucleus of Purkinje cells are not sufficient to induce disease. We suggest that S776 of ataxin-1 also has a critical role in SCA1 pathogenesis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is a growing population of adolescent and young adult (AYA, age 15-39 years) acute leukemia survivors in whom long-term mortality outcomes are largely unknown.
The current study utilized the ...Surveillance, Epidemiology, and End Results (SEER) registry to assess long-term outcomes of AYA acute leukemia 5-year survivors. The impact of diagnosis age, sex, race/ethnicity, socioeconomic status, and decade of diagnosis on long-term survival were assessed utilizing an accelerated failure time model.
A total of 1,938 AYA acute lymphoblastic leukemia (ALL) and 2,350 AYA acute myeloid leukemia (AML) survivors diagnosed between 1980 and 2009 were included with a median follow-up of 12.3 and 12.7 years, respectively. Ten-year survival for ALL and AML survivors was 87% and 89%, respectively, and 99% for the general population. Survival for AYA leukemia survivors remained below that of the age-adjusted general population at up to 30 years of follow-up. Primary cancer mortality was the most common cause of death in early survivorship with noncancer causes of death becoming more prevalent in later decades of follow-up. Male AML survivors had significantly worse survival than females (survival time ratio: 0.61, 95% confidence interval: 0.45-0.82).
AYA leukemia survivors have higher mortality rates than the general population that persist for decades after diagnosis.
While there have been improvements in late mortality, long-term survival for AYA leukemia survivors remains below that of the general population. Studies investigating risk factors for mortality and disparities in late effects among long-term AYA leukemia survivors are needed.
PURPOSE:
METHODS:
RESULTS:A total of 22 studies, with 1,852 females, were included. Infertility rate was 12 percent before restorative proctocolectomy and 26 percent after, among 945 patients in ...seven studies. The incidence of sexual dysfunction was 8 percent preoperatively and 25 percent postoperatively (7 studies, n = 419). Two studies (n = 62) reported no urinary dysfunction in patients undergoing restorative proctocolectomy. There was an increased incidence of cesarean section after restorative proctocolectomy. During the third trimester of pregnancy, there was an increase in stool frequency by 1.15 stools per day compared with before pregnancy frequency (n = 49 95 percent confidence interval, 0.28-2.03 P = 0.01 chi-squared statistic, 0.04 P = 0.84). No significant differences were seen in pouch function after vaginal delivery (n = 456; weighted mean difference, 0.23; 95 percent confidence interval, 0.43-0.88; P = 0.49; chi-squared statistic, 1.29; P = 0.26).
CONCLUSIONS:
OBJECTIVES:Prophylactic colectomy at a premalignant stage is the cornerstone of management of familial adenomatous polyposis (FAP). Before surgery, colonoscopy surveillance is recommended in children ...with FAP. This study aimed to examine the natural history of FAP in children by evaluating adenoma progression and factors influencing timing of colectomy.MethodPatients with FAP younger than 18 years at first surveillance colonoscopy and who had undergone more than 1 colonoscopy were identified. Demographic, endoscopic, genetic, and surgical data were retrieved. Cumulative adenoma (polyp) counts were obtained while accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing the timing of colectomy were evaluated.
RESULTS:Eighty-four patients (50% boys; mean age at first colonoscopy 13 years standard deviation 1.97) were identified, of which 83 had a family history of FAP. At first colonoscopy, 67 (79%) had <100 adenomas and 29 (35%) had colonic polyps identified despite rectal sparing. The median rate of polyp progression per patient was 12.5 polyps/year (range 0–145). Of the 45 (54%) patients who had undergone surgery, 41 (91%) underwent colectomy with ileorectal or ileodistal sigmoid anastomosis. Polyp progression did not alter the choice of surgical intervention in any patient.
CONCLUSION:Our results suggest that adenoma number remains relatively stable in the majority of children under surveillance. Tailored surveillance intervals according to phenotype are a more appropriate strategy as recommended by recently published guidelines.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Background Social needs inhibit receipt of timely medical care. Social needs screening is a vital part of comprehensive cancer care, and patient navigators are well-positioned to screen for ...and address social needs. This mixed methods project describes social needs screening implementation in a prospective pragmatic patient navigation intervention trial for minoritized women newly diagnosed with breast cancer. Methods Translating Research Into Practice (TRIP) was conducted at five cancer care sites in Boston, MA from 2018 to 2022. The patient navigation intervention protocol included completion of a social needs screening survey covering 9 domains (e.g., food, transportation) within 90 days of intake. We estimated the proportion of patients who received a social needs screening within 90 days of navigation intake. A multivariable log binomial regression model estimated the adjusted rate ratios (aRR) and 95% confidence intervals (CI) of patient socio-demographic characteristics and screening delivery. Key informant interviews with navigators (n = 8) and patients (n = 21) assessed screening acceptability and factors that facilitate and impede implementation. Using a convergent, parallel mixed methods approach, findings from each data source were integrated to interpret study results. Results Patients’ (n = 588) mean age was 59 (SD = 13); 45% were non-Hispanic Black and 27% were Hispanic. Sixty-nine percent of patients in the navigators’ caseloads received social needs screening. Patients of non-Hispanic Black race/ethnicity (aRR = 1.25; 95% CI = 1.06–1.48) and those with Medicare insurance (aRR = 1.13; 95% CI = 1.04–1.23) were more likely to be screened. Screening was universally acceptable to navigators and generally acceptable to patients. Systems-based supports for improving implementation were identified. Conclusions Social needs screening was acceptable, yet with modest implementation. Continued systems-based efforts to integrate social needs screening in medical care are needed.
Full text
Available for:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MUTYH-associated polyposis (MAP) is similar to familial adenomatous polyposis (FAP), in that it increases the risk for duodenal adenomas and cancer. Almost all patients with FAP develop duodenal ...adenomas and 5% develop duodenal cancer. Little is known about the prevalence of duodenal adenomas and cancer in patients with MAP, but current surveillance recommendations are the same for patients with FAP-they should begin surveillance when they are 25 years old. We aimed to assess the prevalence, extent, and progression of duodenal adenomas in patients with MAP and evaluate upper gastrointestinal tract surveillance recommendations.
In a retrospective study, we collected data on all patients (n = 92) with MAP undergoing surveillance esophagogastroduodenoscopy from registries at St Mark's Hospital (London, UK) and the Academic Medical Center (Amsterdam, The Netherlands) from 2002 through 2014. We collected information on adenoma development, age at adenoma detection, interventions, and disease progression.
Duodenal adenomas were detected in 31 patients (34%), at a median age of 50 years. When duodenal polyposis first was detected, it was Spigelman stages I or II in 84% of patients; most had few small polyps, without high-grade dysplasia or villous features. Subsequent esophagogastroduodenoscopy evaluation of 18 of these patients found that 14 (78%) had Spigelman stages 0 to II disease (median follow-up period, 7.8 y). Disease progressed in stage in 6 patients, over 9.5 years, because of lesion size or villous features (2 reached stage IV disease). Adenomas were down-staged in 8 patients after biopsy or polypectomy analyses, and were unchanged for 3 patients.
In a data analysis from 92 patients with MAP, duodenal polyposis seemed to develop less frequently than in patients with FAP, and developed at a later age. Increasing lesion size and villous change appear to promote adenoma progression, rather than polyp number or dysplasia. It may be time to consider a new staging system for patients with MAP, to better determine disease severity and surveillance strategies.
PDF
