Antifungal prophylaxis during 7 + 3 induction chemotherapy for acute myeloid leukemia is associated with improved survival, in a setting with low incidence of invasive mold infections.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myeloid leukemia (AML). In this patient population, antifungal prophylaxis (AP) has been associated with decreased incidence of IFIs and better survival. However, some centers have not adopted AP during induction chemotherapy for AML, as it is unclear whether AP improves outcomes in settings where the incidence of invasive mold infections is low. We retrospectively assessed the differences in clinical outcomes and resource utilization in patients undergoing 7 + 3 induction chemotherapy for AML, after implementing a policy of AP as part of a dedicated inpatient malignant hematology service (HS) at Rhode Island Hospital. Between January 1, 2007 and April 1, 2019, 56 patients with AML received AP during 7 + 3 induction chemotherapy and 52 patients did not, without significant differences in their baseline characteristics. Use of AP was associated with less proven or probable IFI (0% vs. 6%, P = 0.1) and lower all-cause in-hospital mortality (7% vs. 21%, P < 0.05), without significant increases in resource utilization or toxicities. Empiric and targeted antifungal therapies were more frequently started in the non-AP group (69%) than changed in the AP group (41%, P < 0.005). Having a dedicated inpatient malignant hematology service was also associated with improved outcomes. However, use of AP was associated with better survival (30-day post-induction survival log-rank P < 0.05), prior to the implementation of this clinical service as well, which is suggestive of an independent benefit from AP.

Detection of chemical exchange in methyl groups of macromolecules.

The zero- and double-quantum methyl TROSY Hahn-echo and the methyl 1H-1H dipole-dipole cross-correlation nuclear magnetic resonance experiments enable estimation of multiple quantum chemical exchange broadening in methyl groups in proteins. The two relaxation rate constants are established to be linearly dependent using molecular dynamics simulations and empirical analysis of experimental data. This relationship allows chemical exchange broadening to be recognized as an increase in the Hahn-echo relaxation rate constant. The approach is illustrated by analyzing relaxation data collected at three temperatures for E. coli ribonuclease HI and by analyzing relaxation data collected for different cofactor and substrate complexes of E. coli AlkB.

Enhanced spectral density mapping through combined multiple-field deuterium 13CH2D methyl spin relaxation NMR spectroscopy.

Quadrupolar relaxation of 2H (D) nuclear spins is a powerful probe of conformational dynamics in biological macromolecules. Deuterium relaxation rate constants are determined by the spectral density function for reorientation of the C-D bond vector at zero, single-quantum, and double-quantum 2H frequencies. In the present work, 2H relaxation rate constants were measured for an E. coli ribonuclease H [U-2H, 15N] ILV-[13CH2D] sample using 400, 500, 800, and 900 MHz NMR spectrometers and analyzed by three approaches to determine spectral density values. First, data recorded at each static magnetic field were analyzed independently. Second, data recorded at 400 and 800 MHz were analyzed jointly and data recorded at other fields were analyzed independently. Third, data recorded at 400 and 500 MHz were interpolated to 450 MHz, and the resulting two pairs of data, corresponding to 400 MHz/800 MHz and 450 MHz/900 MHz, were analyzed jointly. The second and third approaches rely on the identity between the double quantum frequency at the lower field and the single quantum frequency at the higher field. Spectral density values for 32 of the 48 resolvable ILV methyl resonances were fit by the Lipari-Szabo model-free formalism and used to validate the three methods. The three spectral density mapping methods performed equally well in cross validation with data recorded at 700 MHz. However, the third method yielded approximately 10-15% more precise estimates of model-free parameters and consequently provides a general strategy for analysis of 2H spin relaxation data in biological macromolecules.

Analysis of NMR Spin-Relaxation Data Using an Inverse Gaussian Distribution Function.

Spin relaxation in solution-state NMR spectroscopy is a powerful approach to explore the conformational dynamics of biological macromolecules. Probability distribution functions for overall or internal correlation times have been used previously to model spectral density functions central to spin-relaxation theory. Applications to biological macromolecules rely on transverse relaxation rate constants, and when studying nanosecond timescale motions, sampling at ultralow frequencies is often necessary. Consequently, appropriate distribution functions necessitate spectral density functions that are accurate and convergent as frequencies approach zero. In this work, the inverse Gaussian probability distribution function is derived from general properties of spectral density functions at low and high frequencies for macromolecules in solution, using the principle of maximal entropy. This normalized distribution function is first used to calculate the correlation function, followed by the spectral density function. The resulting model-free spectral density functions are finite at a frequency of zero and can be used to describe distributions of either overall or internal correlation times using the model-free ansatz. To validate the approach, 15N spin-relaxation data for the bZip transcription factor domain of the Saccharomyces cerevisiae protein GCN4, in the absence of cognate DNA, were analyzed using the inverse Gaussian probability distribution for intramolecular correlation times. The results extend previous models for the conformational dynamics of the intrinsically disordered, DNA-binding region of the bZip transcription factor domain.

Microangiopathic hemolytic anemia in pregnancy.

Microangipathic hemolytic anemia (MAHA) is a serious diagnosis and difficult to manage in pregnant patients as multiple life threatening conditions could present with MAHA. ADAMTS13 enzyme activity can be affected during pregnancy with multiple factors. A persistent extremely low ADAMTS13 enzyme activity levels, without an inhibitor, after the delivery was an important factor to establish the diagnosis. We present a case of likely congenital ADAMST13 deficiency that manifested for the first time in a pregnant woman at week 37 of pregnancy.

An update in the endoscopic management of gastric cancer.

PURPOSE OF REVIEW: Gastric cancer remains a leading cause of mortality worldwide and gastroenterologists are playing an increasingly larger role in its management. This article reviews the endoscopic management of gastric cancer, with emphasis on recent advances in the field. RECENT FINDINGS: Long-term studies comparing surgery and endoscopic resection for early gastric cancer have shown no difference in 10-year survival rates. Second-look endoscopy, performed 2 days after endoscopic submucosal dissection (ESD) to address the concern of delayed bleeding, may not affect rebleeding rates. Magnesium, proton pump inhibitors, and bupivacaine may help reduce post-ESD pain. New devices such as the Clutch Cutter and EndoLifter may help make ESD easier and safer. SUMMARY: Endoscopic therapy for early gastric cancer is becoming increasingly popular and innovations are constantly being made to improve technique and technology. This review focuses on the latest approaches to the endoscopic management of gastric cancer.

Advances in Surgical Management of Intra-articular Calcaneus Fractures.

Intra-articular calcaneus fractures are commonly sustained after high-energy trauma, and a variety of techniques exists for anatomic reduction and surgical fixation. Traditional approaches using an extended L-shaped lateral incision with lateral plating for open reduction and internal fixation have relatively high complication rates. Common complications include hematoma formation, skin edge necrosis, wound breakdown, and superficial or deep infection. As a result, less invasive techniques have been developed in recent years, including limited-incision sinus tarsi open reduction and internal fixation, percutaneous fixation, and arthroscopic-assisted fixation. These techniques are associated with lower complication rates and equivalent clinical and radiographic outcomes in certain fracture patterns and patient populations.

External beam radiation therapy for orthopaedic pathology.

External beam radiation therapy is essential in the management of a wide spectrum of musculoskeletal conditions, both benign and malignant, including bony and soft-tissue sarcomas, metastatic tumors, pigmented villonodular synovitis, and heterotopic ossification. Radiation therapy, in combination with surgery, helps reduce the functional loss from cancer resections. Although the field of radiation therapy is firmly rooted in physics and radiation biology, its indications and delivery methods are rapidly evolving. External beam radiation therapy mainly comes in the form of four sources of radiotherapy: protons, photons, electrons, and neutrons. Each type of energy has a unique role in treating various pathologies; however, these energy types also have their own distinctive limitations and morbidities.

Extended indications for foot and ankle arthroscopy.

Advances in foot and ankle arthroscopy have allowed surgeons to diagnose and treat a broadening array of disorders that were previously limited to open procedures. Arthroscopy of the posterior ankle, subtalar joint, and first metatarsophalangeal joint and tendoscopy can be used to address common foot and ankle ailments, with the potential benefits of decreased pain, fast recovery, and low complication rates. Posterior ankle and subtalar arthroscopy can be used to manage impingement, arthrofibrosis, synovitis, arthritis, fractures, and osteochondral defects. First metatarsophalangeal joint arthroscopy can address osteophytes, chronic synovitis, osteochondral defects, and degenerative joint disease. Tendoscopy is a minimally invasive alternative for evaluation and débridement of the Achilles, posterior tibial, flexor hallucis longus, and peroneal tendons.

Do retrieval analysis and blood metal measurements contribute to our understanding of adverse local tissue reactions?

BACKGROUND: Metal-on-metal (MoM) total hip arthroplasties (THAs) and the head-neck and neck-body junctions in modular THA are associated with a variety of local and systemic reactions to their related wear and corrosion products. Although laboratory testing is available, the relationship between laboratory values--including serum metal ion levels--and adverse local tissue reactions (ALTRs) remains controversial and incompletely characterized. QUESTIONS/PURPOSES: (1) What is the range of serum metal levels associated with ALTR in patients who have MoM THAs or corrosion at the head-neck and neck-body junctions in metal-on-polyethylene (or ceramic-on-polyethylene) THAs? (2) How much wear occurs in patients with MoM total hips? (3) Is there evidence of a dose-response relationship between wear and ALTR? METHODS: PubMed and Embase databases were reviewed for English-language studies assessing serum metal levels in the presence of ALTR and papers describing the results of wear measurements from revised MoM implants and ALTR histopathology were systematically reviewed. Reported linear wear data were separated into groups with ALTR and without ALTR as listed in individual papers and graphed to determine whether a dose-response relationship was present between wear and ALTR. Overall, 15 studies including 338 hips with ALTR with corresponding serum metal levels were identified and analyzed. Twelve studies reported the wear depth or volume of MoM components from patients with a variety of local reactions. Two studies investigated corrosion at the head-neck and neck-body junctions in metal-on-polyethylene THA. There was a high level of variability and study heterogeneity, and so data pooling (meta-analysis) could not be performed. RESULTS: Average reported metal concentrations were elevated above established normal values in patients with ALTR (cobalt concentrations ranged from 5 to 40 ppb, and chromium levels ranged from 5 to 54 ppb). Whereas several studies demonstrated that patients with ALTR had higher average linear wear of the bearing surfaces, this finding was not made in all studies that we identified in this systematic review. Because of this high degree of variability, no clear dose-response relationship between wear and ALTR could be established. CONCLUSIONS: Serum metal level analysis and implant retrieval analysis both contribute to the understanding of ALTR. Serum metal levels generally are elevated in the presence of ALTR but should not be used in isolation for clinical decision-making. Many but not all patients with ALTR, including those with pseudotumors, demonstrate high wear, but more data and more systematic descriptions of the histopathology are needed to define the amount of wear that induces adverse reactions.

The outcomes and surgical techniques of the latarjet procedure.

PURPOSE: To determine the optimal position and orientation of the coracoid bone graft for the Latarjet procedure for recurrent instability in patients with recurrent anterior instability and high degrees of glenoid bone loss. METHODS: A systematic review of the literature including the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980-2012), and Medline (1980-2012) was conducted. The following search teams were used: glenoid bone graft, coracoid transfer, glenoid rim fracture, osseous glenoid defect, and Latarjet. Studies deemed appropriate for inclusion were then analyzed. Study data collected included level of evidence, patient demographic characteristics, preoperative variables, intraoperative findings, technique details, and postoperative recovery and complications where available. RESULTS: The original search provided a total of 344 studies. A total of 334 studies were subsequently excluded because they were on an irrelevant topic, used an arthroscopic technique, or were not published in English or because they were review articles, leaving 10 studies eligible for inclusion. Given the different methods used in each of the studies included in the review, descriptive analysis was performed. The duration of follow-up ranged from 6 months to 14.3 years postoperatively. With the exception of 2 studies, all authors reported on recurrent shoulder instability after Latarjet reconstruction; the rate of recurrent anterior shoulder instability ranged from 0% to 8%. Overall patient satisfaction was listed in 4 studies, each of which reported good to excellent satisfaction rates of more than 90% at final follow-up. CONCLUSIONS: As noted in this review, the current literature on Latarjet outcomes consists mostly of retrospective Level IV case series. Although promising outcomes with regard to a low rate of recurrent instability have been seen with these reports, it should be noted that subtle variations in surgical technique, among other factors, may drastically impact the likelihood of glenohumeral degenerative changes arising in these patients. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Parsing Dynamics of Protein Backbone NH and Side-Chain Methyl Groups using Molecular Dynamics Simulations.

Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into biological function. The present work describes an extensive set of backbone NH and side-chain methyl group generalized order parameters for the Escherichia coli ribonuclease HI (RNH) enzyme derived from 2-µs microsecond MD simulations using the OPLS4 and AMBER-FF19SB force fields. The simulated generalized order parameters are compared with values derived from NMR 15N and 13CH2D spin relaxation measurements. The squares of the generalized order parameters, S2 for the N-H bond vector and Saxis2 for the methyl group symmetry axis, characterize the equilibrium distribution of vector orientations in a molecular frame of reference. Optimal agreement between simulated and experimental results was obtained by averaging S2 or Saxis2 calculated by dividing the simulated trajectories into 50 ns blocks (∼five times the rotational diffusion correlation time for RNH). With this procedure, the median absolute deviations (MAD) between experimental and simulated values of S2 and Saxis2 are 0.030 (NH) and 0.061 (CH3) for OPLS4 and 0.041 (NH) and 0.078 (CH3) for AMBER-FF19SB. The MAD between OPLS4 and AMBER-FF19SB are 0.021 (NH) and 0.072 (CH3). The generalized order parameters for the methyl group symmetry axis can be decomposed into contributions from backbone fluctuations, between-rotamer dihedral angle transitions, and within-rotamer dihedral angle fluctuations. Analysis of the simulation trajectories shows that (i) backbone and side chain conformational fluctuations exhibit little correlation and that (ii) fluctuations within rotamers are limited and highly uniform with values that depend on the number of dihedral angles considered. Low values of Saxis2, indicative of enhanced side-chain flexibility, result from between-rotamer transitions that can be enhanced by increased local backbone flexibility.

Characterizing after-hours hematology/oncology clinic calls.

BACKGROUND: After-hour calls can be resource intensive and remain a significant challenge to medical practices, though they have historically been poorly or non-reimbursable services. This study reviews after-hour calls from hematology/oncology patients at a cancer center to characterize after-hour care needs, identify care gaps, and look for opportunities to improve outpatient healthcare delivery. METHODS: This descriptive, retrospective Institutional Review Board-approved study analyzed patient calls between June 2015 to February 2021 in an academic hematology/oncology practice. Data from 500 calls were reviewed and cataloged into a database including patient demographics, clinical history, and information surrounding the call (e.g., primary reason for the call, outcome of the call). Calls were also categorized as being urgent or not from a patient or provider's perspective. RESULTS: Among 500 calls, representing 398 unique patients, the average patient was 62 years old and 52% of calls were from females. Most calls were made to report symptoms (65%), followed by calls to follow-up on labs, tests, or imaging (13%), and clarifying treatment plans (10%). Oncology patients represented 67% of calls and hematology (malignant and benign) patients represented 33%. More specifically, patients with gastrointestinal cancer (25%), hematologic malignancies (24%), and thoracic cancer (13%) represented the diagnoses with the highest call volume. CONCLUSIONS: This study explores the complexity and variety of after-hour cancer patient calls. By systematically exploring patient calls, this data can provide insight into patients' needs outside of regular clinic times and help practices develop strategies to anticipate these needs, reduce after-hour call burden, and improve overall quality of care.

Acute Liver Failure With Liver Enzymes >5,000 in Sickle Cell Disease.

Sickle cell disease is a hemoglobinopathy often complicated by painful vaso-occlusive episodes, acute chest syndrome, stroke, and myocardial infarction. Sickle cell intrahepatic cholestasis (SCIC) is a rare and potentially fatal complication of sickle cell disease. SCIC is thought to involve progressive hepatic injury due to sickling within sinusoids. We present the case of a young patient with SCIC and acute liver failure, requiring prompt treatment with exchange transfusion. Our case describes features that should raise suspicion for hepatic failure in SCIC and highlights exchange transfusion as a successful management approach in similar patients with an otherwise high risk of mortality.

Correction of intermetatarsal angle in hallux valgus using small suture button device.

BACKGROUND: Hallux valgus is a common foot ailment causing pain and disability, and correction of the intermetatarsal angle (IMA) deformity is often accomplished using a first metatarsal distal or proximal osteotomy. These osteotomies can be technically challenging and may lead to complications such as loss of fixation, shortening of the first metatarsal, avascular necrosis, malunion, and nonunion. Endobuttons (Mini TightRope device) provide an alternative to first metatarsal osteotomies for correction of the IMA. The purpose of this preliminary study was to determine the short-term clinical and radiographic outcomes of hallux valgus correction using the Mini TightRope. METHODS: A total of 14 cases of hallux valgus correction using the Mini TightRope technique with a 1.1-mm drill and mini-buttress plate were reviewed. Clinical examinations and radiographs were performed preoperatively and postoperatively at 1-week (non-weight-bearing), 3-month (weight-bearing), and 6-month (weight-bearing) follow-up. RESULTS: The overall 1-week postoperative decreases in IMA and hallux valgus angle (HVA) of all cases compared with preoperative status were 9 degrees and 28 degrees, respectively. Decreases in IMA and HVA continued at 3 months postoperatively but to a lesser extent, with decreases of 7 degrees and 20 degrees, respectively. Reductions in IMA and HVA were maintained through 6 months of follow-up compared with preoperatively, with IMA and HVA decreases of 6 degrees and 19 degrees, respectively. Two minor soft-tissue complications and 1 intraoperative second metatarsal fracture were treated with a buttress plate, with uneventful healing. CONCLUSIONS: Overall short-term results demonstrated notable improvements in IMA and HVA with use of the Mini TightRope, and few early complications were associated with the procedure.