Citations

The purpose of this study was to evaluate the effect of wrapping bioabsorbable nerve conduit around primary suture repair on motor nerve regeneration in a rat model. Forty rats were randomly divided into two experimental groups according to the type of repair of the rat sciatic nerve: group I had primary suture repair; group II had primary suture repair and bioabsorbable collagen nerve conduit (NeuraGen® 1.5 mm, Integra LifeSciences Corp., Plainsboro, NJ) wrapped around the repair. At 12 weeks, no significant differences in the percentage of recovery between the two groups were observed with respect to compound muscle action potentials, isometric muscle force, and muscle weight (P = 0.816, P = 0.698, P = 0.861, respectively). Histomorphometric analysis as compared to the non‐operative sites was also not significantly different between the two groups in terms of number of myelinated axons, myelinated fiber area, and nerve fiber density (P = 0.368, P = 0.968, P = 0.071, respectively). Perineural scar tissue formation was greater in primary suture repair group (0.36 ± 0.15) than in primary repair plus conduit wrapping group (0.17 ± 0.08). This difference was statistically significant (P < 0.001). Wrapping bioabsorbable nerve conduit around primary nerve repair can decrease perineural scar tissue formation. Although the scar‐decreasing effect of bioabsorbable nerve wrap does not translate into better motor nerve recovery in this study, it might have an effect on the functional outcome in humans where scar formation is much more evident than in rats. © 2014 Wiley Periodicals, Inc. Microsurgery 34:562–567, 2014.

ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation.BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG.MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5‐year follow‐up were collected and compared in the two groups.ResultsOne out of three patients exhibited severe lesion calcification (n = 588). Patients with calcified coronaries had an increased mortality at 5‐year follow‐up (17.1% vs. 9.9%, P < 0.001) and a higher event rate of death‐myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P = 0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P = 0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all‐cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02–1.89; P = 0.037) but it was not an independent predictor of the combined end‐points death‐MI or MACE.ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death‐MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. © 2014 Wiley Periodicals, Inc.

Patients with diffuse large B‐cell lymphoma (DLBCL) and pre‐treatment bone marrow (BM) involvement require a restaging BM biopsy to document complete remission (CR). We investigated whether BM assessment by restaging PET‐CT could obviate the need for a repeat BM biopsy. Patients with DLBCL and a positive BM biopsy at diagnosis were identified from the Mayo Clinic Lymphoma Data Base. The concordance of BM status on restaging histopathology and PET‐CT reports and the positive (PPV) and negative predictive value (NPV) of PET‐CT were determined. One thousand eighty patients with DLBCL were evaluated and 69 patients (6%) had DLBCL involving the BM at diagnosis. Of 46 patients who completed frontline chemoimmunotherapy, 34 had a restaging PET‐CT and BM biopsy and were included in the analysis. Thirty‐three patients had a negative BM by both PET‐CT and BM biopsy; one patient had persistent BM involvement by biopsy and PET‐CT. Thus, restaging PET‐CT had 100% PPV and 100% NPV for assessing residual BM disease. The findings were validated in a prospective cohort of 68 DLBCL patients treated on a phase II clinical trial where four patients (6%) had DLBCL involving the BM at diagnosis. All had a negative BM by both restaging BM biopsy and PET‐CT. Compared with the gold standard of BM biopsy, PET‐CT had a 100% NPV to exclude residual BM disease after frontline therapy. If further validated, DLBCL practice guidelines and response criteria could be modified so that BM biopsy is no longer required to document CR if the restaging PET‐CT is negative. Am. J. Hematol. 89:865–867, 2014. © 2014 Wiley Periodicals, Inc.

Background— Decision aids (DAs) increase patient knowledge, reduce decisional conflict, and promote shared decision making (SDM). The extent to which they do so across diverse sociodemographic patient groups is unknown. Methods and Results— We conducted a patient-level meta-analysis of 7 randomized trials of DA versus usual care comprising 771 encounters between patients and clinicians discussing treatment options for chest pain, myocardial infarction, diabetes mellitus, and osteoporosis. Using a random effects model, we examined the impact of sociodemographic patient characteristics (age, sex, education, income, and insurance status) on the outcomes of knowledge transfer, decisional conflict, and patient involvement in SDM. Because of small numbers of people of color in the study population, we were not powered to investigate the role of race. Most patients were aged ≥65 years (61%), white (94%), and women (59%); two thirds had greater than a high school education. Compared with usual care, DA patients gained knowledge, were more likely to know their risk, and had less decisional conflict along with greater involvement in SDM. These gains were largely consistent across sociodemographic patient groups, with DAs demonstrating similar efficacy when used with vulnerable patients such as the elderly and those with less income and less formal education. Differences in efficacy were found only in knowledge of risk in 1 subgroup, with greater efficacy among those with higher education (35% versus 18%; P =0.02). Conclusions— In this patient-level meta-analysis of 7 randomized trials, DAs were efficacious across diverse sociodemographic groups as measured by knowledge transfer, decisional conflict, and patient involvement in SDM. To the extent that DAs increase patient knowledge and participation in SDM, they have potential to impact health disparities related to these factors.

Background— Little is known about the resuscitation preferences of patients with heart failure, how they may change over the course of the disease, and their association with mortality. Methods and Results— We enrolled consecutive Southeastern Minnesota residents with heart failure from October 2007 through September 2011 into a longitudinal study. Information on resuscitation preferences (Full Code or do-not-resuscitate [DNR]) was obtained from medical records through April 1, 2013. Of 608 patients enrolled, 237 died during follow-up. At enrollment, most patients (73.4%) were Full Code, whereas at death, most (78.5%) were DNR. The independent predictors of DNR status at enrollment were advanced age, chronic obstructive pulmonary disease, previous malignancy, and decreased mobility. Patients who were DNR were at increased risk of death (unadjusted hazard ratio, 2.03; 95% confidence interval, 1.48–2.73; P <0.001), but this risk did not persist after adjusting for age, comorbidity, and self-perceived general health (hazard ratio, 0.97; 95% confidence interval, 0.74–1.30; P =0.83). Of 481 patients who were Full Code during follow-up, 22 (4.6%) received cardiopulmonary resuscitation for an in-hospital cardiac arrest. Eight patients survived to hospital discharge; only 2 (9.1% of those receiving cardiopulmonary resuscitation) made a complete recovery and returned home. The median time from a final decision to be DNR until death was only 37 (7,70) days. Conclusions— The resuscitation preferences of patients with heart failure seem to be driven by the decline in clinical status that often accompanies advanced age and multimorbidity. Furthermore, these data suggest that electing DNR status does not independently affect a patient’s risk of death.

Background— Patients undergo major physical and psychological changes after implantation of a left ventricular assist device as destination therapy (DT). We sought to qualitatively study outcomes and attitudes of patients after DT. Methods and Results— Ambulatory outpatients with DT at our institution were invited to be interviewed between June and August 2011. In-person interviews were audio-recorded, transcribed, and analyzed qualitatively using thematic analysis. The study included 12 patients (11 men) from the Midwestern United States with a median age of 71.5 years (range, 33–78 years). Interviews were conducted at a median (range) time of 1.37 (0.43–5.04) years after DT implantation. Most patients were white (n=11), married (n=10), and Christian (n=10). We identified 6 themes commonly discussed by the interviewees: preparedness planning, new lease on life, optimizing support networks, systemic limitations, reflections on time, and communication matters. Analysis revealed that most patients saw DT as their only choice, despite other alternatives. Conclusions— Ambulatory patients reported varied experiences after DT but commonly reported gratitude for improved functional status and a perception of improved symptom burden. Recommendations for improving post-DT care include developing patient support systems, systematizing education for community providers, and expanding respite services.

Objective To evaluate outcomes of the first 18 patients treated with robot‐assisted retroperitoneal lymph node dissection ( RA‐RPLND ) for non‐seminomatous germ cell tumours ( NSGCT ) and paratesticular rhabdomyosarcoma ( RMS ) at our institution. Patients and Methods Between M arch 2008 and M ay 2013, 17 patients underwent RA‐RPLND for NSGCT and one for paratesticular RMS . Data were collected retrospectively on patient demographics, preoperative tumour characteristics, and perioperative outcomes including open conversion rate, lymph node ( LN ) yield, rate of positive LNs , operative time, estimated blood loss ( EBL ), and length of stay ( LOS ). Perioperative outcomes were compared between patients receiving primary RA‐RPLND vs post‐chemotherapy RA‐RPLND . Medium‐term outcomes of tumour recurrence rate and maintenance of antegrade ejaculation were recorded. Results RA‐RPLND was completed robotically in 15 of 18 (83%) patients. LNs were positive in eight of 18 patients (44%). The mean LN yield was 22 LNs . For cases completed robotically, the mean operative time was 329 min, EBL was 103 mL, and LOS was 2.4 days. At a mean (range) follow‐up of 22 (1–58) months, there were no retroperitoneal recurrences and two of 17 (12%) patients with NSGCT had pulmonary recurrences. Antegrade ejaculation was maintained in 91% of patients with a nerve‐sparing approach. Patients receiving primary RA‐RPLND had shorter operative times compared with those post‐chemotherapy (311 vs 369 min, P = 0.03). There was no significant difference in LN yield (22 vs 18 LNs , P = 0.34), EBL (100 vs 313 mL, P = 0.13), or LOS (2.75 vs 2.2 days, P = 0.36). Conclusion This initial selected case series of RA‐RPLND shows that the procedure is safe, reproducible, and feasible for stage I – IIB NSGCT and RMS in the hands of experienced robotic surgeons. Larger studies are needed to confirm the diagnostic and therapeutic utility of this technique.

Abstract Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies. The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary.

Significance We show that DNA double-strand breaks (DSBs) can be repaired by insertion of 50- to 1,000-bp sequences termed “templated-sequence insertions” (TSIs) derived from distant regions of the genome. Additional experiments indicate that the source of template for repair was primarily nuclear RNA. This mode of DNA-DSB repair by insertion is not restricted to experimentally produced breaks but also occurs at the site of spontaneous DNA DSBs in human cells. These TSIs are polymorphic in the human genome, suggesting that some TSIs occur in germ cells or embryos. Recognition of these TSIs is important in interpreting structural variations in short-read sequencing studies and provides additional polymorphic markers for population and evolution studies. This error-prone form of DNA repair may play a role in genetic diseases.