Immunodeficiency: Complement disorders.

The complement system is an important component of innate and adaptive immunity that consists of three activation pathways. The classic complement pathway plays a role in humoral immunity, whereas the alternative and lectin pathways augment the innate response. Impairment, deficiency, or overactivation of any of the known 50 complement proteins may lead to increased susceptibility to infection with encapsulated organisms, autoimmunity, hereditary angioedema, or thrombosis, depending on the affected protein. Classic pathway defects result from deficiencies of complement proteins C1q, C1r, C1s, C2, and C4, and typically manifest with features of systemic lupus erythematosus and infections with encapsulated organisms. Alternative pathway defects due to deficiencies of factor B, factor D, and properdin may present with increased susceptibility to Neisseria infections. Lectin pathway defects, including Mannose-binding protein-associated serine protease 2 (MASP2) and ficolin 3, may be asymptomatic or lead to pyogenic infections and autoimmunity. Complement protein C3 is common to all pathways, deficiency of which predisposes patients to severe frequent infections and glomerulonephritis. Deficiencies in factor H and factor I, which regulate the alternative pathway, may lead to hemolytic uremic syndrome. Disseminated Neisseria infections result from terminal pathway defects (i.e., C5, C6, C7, C8, and C9). Diagnosis of complement deficiencies involves screening with functional assays (i.e., total complement activity [CH50], alternative complement pathway activity [AH50], enzyme-linked immunosorbent assay [ELISA]) followed by measurement of individual complement factors by immunoassay. Management of complement deficiencies requires a comprehensive and individualized approach with special attention to vaccination against encapsulated bacteria, consideration of prophylactic antibiotics, treatment of comorbid autoimmunity, and close surveillance.

Hymenoptera venom skin testing: Adopting an accelerated test protocol.

BACKGROUND: The standard method of Hymenoptera venom intradermal skin test is performed at a starting concentration of 0.001 to 0.01 µg/mL and increased by 10-fold concentrations until positive or a maximum concentration of 1 µg/mL. Accelerated methods that start at higher concentrations have been reported as safe; however, many institutions have not adopted this approach. OBJECTIVE: To compare the outcome and safety of standard and accelerated venom skin test protocols. METHODS: This was a retrospective chart review of patients with suspected venom allergy who underwent skin testing at 4 allergy clinics within a single health care system from 2012 to 2022. Demographic data, test protocol (standard vs accelerated), test results, and adverse reactions were reviewed. RESULTS: Of 134 patients who underwent standard venom skin test, 2 (1.5%) experienced an adverse reaction, whereas none of the 77 patients who underwent accelerated venom skin test experienced an adverse reaction. One patient, with a history of chronic urticaria, experienced urticaria. The other experienced anaphylaxis requiring an epinephrine although had tested negative to all venom concentrations. Within the standard testing protocol, more than 75% of the positive results occurred at concentrations of 0.1 or 1 µg/mL. Within the accelerated testing protocol, more than 60% of the positive results occurred at 1 µg/mL. CONCLUSION: The study underscores the overall safety of venom intradermal skin test. Most of the positive results occurred at 0.1 or 1 µg/mL. Adopting an accelerated approach would reduce time and cost associated with testing.

Imported fire ant immunotherapy prescribing patterns in a large health care system during an 11-year period.

BACKGROUND: The first large-scale evaluation of prescribing patterns for imported fire ant (IFA) in a large US health care system was published by Haymore et al in 2009. In this first evaluation of prescriptions from 1990 to 2007, the most often prescribed maintenance IFA prescription was 0.5 mL of 1:200 wt/vol. OBJECTIVE: To provide an updated description of IFA prescribing patterns over the ensuing 11 years from same large health care system. METHODS: We reviewed 1349 new IFA prescriptions written from 2007 to 2018, from a large nationwide health care system, with primary end points being maintenance prescription strength and prescribing patterns. RESULTS: In comparison to the data published by Haymore et al in 2009, which reported that 17% of the prescriptions were written for 0.5 mL of 1:100 wt/vol maintenance, we found that 69% (95% CI: 66.4%-71.4%) of IFA prescriptions written in the past 11 years were for the maintenance concentration of 0.5 mL of 1:100 wt/vol. We further studied the linear trend over time of percentage of prescriptions written for individual concentrations and observed that the percentage of 1:100 wt/vol prescriptions increased 3.5% yearly (R2 = 0.68, P < .001) from 2007 (40.0%, 95% CI: 24.6%-57.7%) to 2018 (84.4%, 95% CI: 77.4%-89.5%). CONCLUSION: Our study shows significant improvement in the accuracy and precision of IFA immunotherapy dosing for patients with IFA hypersensitivity, with ascendancy of 0.5 mL 1:100 wt/vol as the predominant treatment dose. A total of 87% of patients within our study were treated within the parameter recommendations, a stark improvement from findings in the 2009 Haymore study.

Repeated measures analyses of dermatitis symptom evolution in breast cancer patients receiving radiotherapy in a phase 3 randomized trial of mometasone furoate vs placebo (N06C4 [alliance]).

PURPOSE: Radiotherapy-related dermatological toxicities over time have not been well quantified. We examined during and immediately following radiation therapy skin toxicities over time in a randomized study of mometasone furoate vs placebo during breast radiotherapy. MATERIAL AND METHODS: Patients with breast cancer undergoing radiotherapy to the breast or chest wall were randomized. Symptoms related to skin toxicity were addressed weekly using provider-reported Common Terminology Criteria for Adverse Events (CTCAE v3.0) and 4 patient-reported outcomes (PRO) surveys. We applied repeated measures and risk analysis methodologies. RESULTS: One hundred seventy-six patients were enrolled. By CTCAE, significant differences favoring mometasone were detected over time in all toxicities except skin striae, atrophy, and infection. Statistically significant differences between arms at baseline but not over time occurred for all Linear Analog Self-Assessment. Statistically significant differences occurred for all symptoms in the temporal profile of symptoms as measured by PRO surveys (all P < .001). CONCLUSIONS: The use of longitudinal methods enhanced the ability of PRO tools to detect differences between study arms. Our results strengthened the conclusions of the original report that mometasone reduced acute skin toxicities. PRO surveys can accurately assess patients' experiences of symptom type and intensity over time and should be included in future clinical trials. For radiotherapy-related dermatological toxicity, we hypothesized that clinically significant differences over time, if any, can be found by repeated measures. We examined the acute skin toxicities in a randomized study of mometasone vs placebo during breast radiotherapy. For secondary end points, we showed that longitudinal methods enhanced the detection of differences between study arms and strengthened the conclusions from the original report. Frequent patient-reported outcome surveys over time should be included in future clinical trials.

Empowering Pediatricians With Direct Penicillin Challenges: A Promising Delabeling Strategy.

OBJECTIVE: Current literature supports a multidisciplinary approach to penicillin allergy delabeling. Our study aims to review the success rate of penicillin challenges performed at Walter Reed National Military Medical Center Allergy Clinic and assess the reaction rate associated with a direct oral challenge in low-risk patients. MATERIALS AND METHODS: We conducted a retrospective review of the outcomes of pediatric penicillin challenges at the Walter Reed National Military Medical Center Allergy and Immunology clinic from June 2019 to May 2023. A total of 74 challenges were included in this study. Patients were initially screened to assess the date of reaction, nature of reaction, if the reaction was life-threatening, and if the patient was hospitalized or sought emergency medical care for the reported reaction. After completion of the screening questionnaire, a direct graded challenge was performed (without skin testing) if a patient's history was deemed low risk. Patients with a recent reaction or a history of multiple drug allergies were more likely to be directed to skin prick testing and intra-dermal testing with Pre-pen and Penicillin-G prior to challenge. RESULTS: All patients passed all challenges. Thus, there was a 100% pass rate for both direct challenges and skin test with oral challenges. CONCLUSION: Given the low rate of adverse events in this study, expansion of penicillin delabeling in the primary care setting should be considered in patients deemed to be at low risk. It is important for allergists to empower and educate their peers and push forward a movement to create a multidisciplinary approach to penicillin delabeling.

Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics.

BACKGROUND: PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below -150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains. The cryogenic cold chain using liquid nitrogen (LN2) vapour phase (LNVP) cryoshippers, is simpler, more efficient than -80, -20 or 2-8 °C cold chains, and does not use electricity. This study was conducted to evaluate implementation and integration of a cryogenically distributed vaccine at travel and military immunization clinics. METHODS: We conducted sequential 28-day studies evaluating vaccine shipping, storage, maintenance and accession at two US military and two civilian travel health/immunization clinics. In each clinic, personnel were trained in equipment use, procurement and handling of LN2, temperature monitoring and inventory record keeping by in-person or video instruction. RESULTS: Sites required 2-4 h/person for two persons to assimilate and develop the expertise to manage vaccine storage and LNVP operations. LN2 for recharging cryoshippers was delivered every 1-2 weeks. Vaccine ordering, receipt, storage and inventory control was conducted effectively. Simulated single dose vaccine cryovial retrieval and thawing were performed successfully in different travel clinic settings. Continuous temperature monitoring at each site was maintained with only one short excursion above -150 °C (-145 °C) through shipping, use and reverse logistics. Staff, during and at study conclusion, provided feedback that has been incorporated into our models for cold chain logistics. CONCLUSIONS: These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel.

Multisite evaluation of fire ant venom immunotherapy safety and efficacy.

Background: Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings. Objective: Our aims were to determine the baseline rates of IFA sensitization in subjects, describe IFA VIT prescribing patterns across the military health system (MHS), and retrospectively evaluate the safety and efficacy of IFA VIT. Methods: We prospectively compared IFA sensitization in participants with and without an SR to flying Hymenoptera venom. Separately, IFA VIT prescription records were extracted from a centralized repository, and rates were described across the MHS. Additionally, we retrospectively reviewed the clinical course of patients being treated with IFA VIT at 11 military treatment facilities. Results: The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%. Sensitization rates did not differ statistically between the subjects with or without an SR to flying Hymenoptera venom. We found that 60.9% of all MHS IFA VIT prescriptions (491 of 806) were from the 11 facilities in this study. We retrospectively identified 137 subjects actively undergoing IFA VIT. Among the subjects actively undergoing IFA VIT, 28 reported an SR to IFA venom and repeat stings by IFAs after reaching VIT maintenance, and 85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT. Conclusion: This study's results align with those of prior IFA sensitization reports. A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events.

Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood.

Importance: Allergic diseases are prevalent in childhood. Early exposure to medications that can alter the microbiome, including acid-suppressive medications and antibiotics, may influence the likelihood of allergy. Objective: To determine whether there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood. Design, Setting, and Participants: A retrospective cohort study was conducted in 792 130 children who were Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013, with continued enrollment from within 35 days of birth until at least age 1 year. Children who had an initial birth stay of greater than 7 days or were diagnosed with any of the outcome allergic conditions within the first 6 months of life were excluded from the study. Data analysis was performed from April 15, 2015, to January 4, 2018. Exposures: Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H2RA), proton pump inhibitor (PPI), or antibiotic. Main Outcomes and Measures: The main outcome was allergic disease, defined as the presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy. Results: Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H2RA, 13 687 (1.7%) were prescribed a PPI, and 131 708 (16.6%) were prescribed an antibiotic during the first 6 months of life. Data for each child were available for a median of 4.6 years. Adjusted hazard ratios (aHRs) in children prescribed H2RAs and PPIs, respectively, were 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis. Conclusions and Relevance: This study found associations between the use of acid-suppressive medications and antibiotics during the first 6 months of infancy and subsequent development of allergic disease. Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit.

Prediction of radial distance of extraprostatic extension from pretherapy factors.

PURPOSE: Extraprostatic extension (EPE) of tumor conveys an adverse prognosis in early-stage prostate cancer. Previous studies reported on the linear and radial distance of EPE (EPEr) as measured from the prostate edge. In this study, the correlation of the EPEr from a large whole mount prostatectomy series was determined with respect to the needle biopsy and prostatectomy specimen findings. METHODS AND MATERIALS: In a 24-month period, 404 patients underwent radical prostatectomy and the specimens were whole mounted. The preoperative records, biopsy findings, and EPEr from these specimens were evaluated. RESULTS: The range of the EPEr distance was 0.0-5.7 mm. A three-category model was used that included 283 patients (70%) with no EPE, 59 (15%) with "near EPE" (range, 0.01-0.59 mm), and 62 (15%) with "far EPE" (>or=0.6 mm). Univariate analysis revealed that patient age and prostate volume did not correlate with EPEr, in contrast to all other factors evaluated. Multivariate analysis identified the preoperative serum prostate-specific antigen, the percentage of cancer in the biopsy cores, and clinical tumor stage as significant. However, the Gleason score was not associated with the EPEr. Greater discrimination was possible in estimating the probability of extension in the "near" category than in the "far" category. CONCLUSION: EPEr is associated with the preoperative prostate-specific antigen level, percentage of cancer in the biopsy cores, and clinical tumor stage. These data might be useful in planning local therapies for prostate cancer, but additional studies identifying factors associated with EPEr beyond 3-5 mm could have relevance regarding the appropriate radiotherapeutic management strategies.

Factors associated with the frequency of self-intermittent catheterization after prostate brachytherapy.

PURPOSE: Urinary obstructive symptoms are the most common side effects of transperineal interstitial permanent prostate brachytherapy (TIPPB). Self-intermittent catheterization (SIC) can be used to relieve urinary retention. This study evaluated the factors associated with the probability of a patient performing SIC after TIPPB. METHODS AND MATERIALS: We prospectively evaluated 204 patients who underwent TIPPB at Mayo Clinic Scottsdale (MCS). All patients were taught to perform SIC before implant and were instructed to do so if they could not urinate at any time after the procedure. RESULTS: Of the 204 patients, 22 patients (11%) received (103)Pd seeds and 182 patients (89%) received (125)I. Thirty-seven (18%) patients received external-beam radiotherapy (XRT) in addition to the TIPPB. SIC was performed by 69 (34%) of the 204 patients. Factors that were significantly associated with a lower frequency of SIC were prostate volumes < or = 34.2 cm(3) (p = 0.005), < or = 137 seeds implanted (p = 0.04), prostate-specific antigen (PSA) levels < or = 6.35 (p = 0.03), American Urological Association (AUA) score < or = 10 (p = 0.01), the use of (125)I (p = 0.03), and the addition of XRT to the implant (p = 0.02). CONCLUSIONS: Significant associations were observed between the frequency of SIC and the number of seeds implanted, AUA scores, prostate volume, PSA levels, addition of XRT, and isotope used. Whereas the first four of these factors may be surrogates for prostate volume and obstructive symptoms in general, the last two factors are related to treatment decisions. These findings may aid in better patient selection and therapeutic decisions. Additionally, this information may provide a clearer understanding of the urinary side effects of TIBBP.

Radiation exposure to operating room personnel during transperineal interstitial permanent prostate brachytherapy.

PURPOSE: To identify factors associated with radiation exposure (RE) to operating room personnel during transperineal interstitial permanent prostate brachytherapy (TIPPB). METHODS AND MATERIALS: Between May 1998 and December 2000, 155 patients underwent TIPPB with fluoroscopic and ultrasound guidance. Data for each case included: operating room time (OT), anesthesia time (AT), fluoroscopy time (FT), number and type of seed implanted, total seed activity, and resident participation. RESULTS: Personnel RE per case, FT, OT, and AT decreased as case number increased. Whole body badge dose per case decreased from a mean of 0.15+/-0.01 mSv (15+/-1 mrem) in 1998 to 0.074+/-0.011 mSv (7+/-1 mrem) in 2000. Average FT per case decreased from a mean of 17:27 min (range, 10:40-28:23) in 1998 to 12:08 min (range, 6:40-31:00) in 2000. Resident participation was associated with increased FT. Mean whole body and ring badge doses for the treating radiation oncologist were 0.0076 mSv/min (0.76 mrem/min) and 0.05 mSv/min (5.26 mrem/min) of FT, respectively. CONCLUSIONS: FT was the predominant factor that related to RE during TIPPB. Treating radiation oncologists were exposed to less than 20 mSv per 100 cases, significantly less than other fluoroscopically guided procedures. Nonetheless, appropriate radiation exposure precautions during TIPPB should continue.

Selective identification of different brachytherapy sources, ferromagnetic seeds, and fiducials in the prostate using an automated seed sorting algorithm.

PURPOSE: Routine permanent prostate brachytherapy (PPB) includes CT-based postimplant dosimetry (PID). A method of identifying different source types from CT data in the same implant volume is described. METHODS AND MATERIALS: A previously described automatic method for seed localization using CT data is used in this study. Two cases were analyzed: a PPB case with (103)Pd followed by salvage (125)I implantation, both performed at another institution, and a cadaver case where 4 different seed types, including ferromagnetic seeds, and fiducials were implanted. RESULTS: Automatic segregation of different seed types with minimal manual correction is demonstrated using the described localization algorithm. The process is confirmed accurate by comparison of plain film radiographs to CT data and digitally reconstructed radiographs. CONCLUSION: Unique identification of different source types, including PPB seeds, fiducial markers, and ferromagnetic seeds in permanent implants is possible and permits dosimetric analyses that are spatially coincident.

Building a cardiology practice.

This study was designed to quantify the clinical and marketing effectiveness of the Pocket EKG Clinical Based Marketing Program by measuring its impact on new patient visits, patient satisfaction, payor negotiations, and patient management at Pikes Peak Cardiology (PPC), Colorado Springs, Colorado. New patient visits were found to increase by 22% for 6.5 consecutive years. Ninety-two percent of patients surveyed found that the Pocket EKG Card promoted loyalty to the cardiology practice. The Pocket EKG Patient Satisfaction Survey was proven to satisfy Health Plan Employer Data and Information Set (HEDIS) guidelines as required in payor contracting. Finally, access to a baseline electrocardiogram contributed to a 54% reduction in unnecessary hospitalization. The Pocket EKG Clinical Based Marketing Program proved to successfully market PPC to its three customers: patients, payors, and primary care physicians.

Comparison of provider-assessed and patient-reported outcome measures of acute skin toxicity during a Phase III trial of mometasone cream versus placebo during breast radiotherapy: the North Central Cancer Treatment Group (N06C4).

PURPOSE: Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider-assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. METHODS AND MATERIALS: Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5-0.7, moderate; and >0.7, strong. RESULTS: CTCAE dermatitis moderately correlated with STAT erythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. CONCLUSIONS: The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4.

PURPOSE: A two-arm, double-blind, randomized trial was performed to evaluate the effect of 0.1% mometasone furoate (MMF) on acute skin-related toxicity in patients undergoing breast or chest wall radiotherapy. METHODS AND MATERIALS: Patients with ductal carcinoma in situ or invasive breast carcinoma who were undergoing external beam radiotherapy to the breast or chest wall were randomly assigned to apply 0.1% MMF or placebo cream daily. The primary study endpoint was the provider-assessed maximal grade of Common Terminology Criteria for Adverse Events, version 3.0, radiation dermatitis. The secondary endpoints included provider-assessed Common Terminology Criteria for Adverse Events Grade 3 or greater radiation dermatitis and adverse event monitoring. The patient-reported outcome measures included the Skindex-16, the Skin Toxicity Assessment Tool, a Symptom Experience Diary, and a quality-of-life self-assessment. An assessment was performed at baseline, weekly during radiotherapy, and for 2 weeks after radiotherapy. RESULTS: A total of 176 patients were enrolled between September 21, 2007, and December 7, 2007. The provider-assessed primary endpoint showed no difference in the mean maximum grade of radiation dermatitis by treatment arm (1.2 for MMF vs. 1.3 for placebo; p = .18). Common Terminology Criteria for Adverse Events toxicity was greater in the placebo group (p = .04), primarily from pruritus. For the patient-reported outcome measures, the maximum Skindex-16 score for the MMF group showed less itching (p = .008), less irritation (p = .01), less symptom persistence or recurrence (p = .02), and less annoyance with skin problems (p = .04). The group's maximal Skin Toxicity Assessment Tool score showed less burning sensation (p = .02) and less itching (p = .002). CONCLUSION: Patients receiving daily MMF during radiotherapy might experience reduced acute skin toxicity compared with patients receiving placebo.

Coordination copolymerization of severely encumbered isoalkenes with ethylene: enhanced enchainment mediated by binuclear catalysts and cocatalysts.

This contribution describes the implementation of the binuclear organotitanium "constrained geometry catalysts" (CGCs), (mu-CH(2)CH(2)-3,3'){(eta(5)-indenyl)[1-Me(2)Si((t)()BuN)](TiMe(2))}(2)[EBICGC(TiMe(2))(2); Ti(2)] and (mu-CH(2)-3,3'){(eta(5)-indenyl)[1-Me(2)Si((t)BuN)](TiMe(2))}(2)[MBICGC(TiMe(2))(2); C1-Ti(2)], in combination with the bifunctional bisborane activator 1,4-(C(6)F(5))(2)BC(6)F(4)B(C(6)F(5))(2) (BN(2)) in ethylene + olefin copolymerization processes. Specifically examined are the classically poorly responsive 1,1-disubstituted comonomers, methylenecyclopentane (C), methylenecyclohexane (D), 1,1,2-trisubstituted 2-methyl-2-butene (E), and isobutene (F). For the first three comonomers, this represents the first report of their incorporation into a polyethylene backbone via a coordination polymerization process. C and D are incorporated via a ring-unopened pathway, and E is incorporated via a novel pathway involving 2-methyl-1-butene enchainment in the copolymer backbone. In ethylene copolymerization, Ti(2) + BN(2) enchains approximately 2.5 times more C, approximately 2.5 times more D, and approximately 2.3 times more E than the mononuclear catalyst analogue [1-Me(2)Si(3-ethylindenyl)((t)BuN)]TiMe(2) (Ti(1)) + B(C(6)F(5))(3) (BN) under identical polymerization conditions. Polar solvents are found to weaken the catalyst-cocatalyst ion pairing, thus influencing the comonomer enchainment selectivity.