Vitamin D and Albumin Deficiency in a Swiss Orthopaedic Surgery In-Patient Cohort.

Background: Vitamin D and protein deficiencies are common conditions in the general population. In Orthopaedic surgery, they can result in wound complications or poor bone healing. The goal of this study was, therefore, to determine the prevalence of vitamin D and albumin deficiencies in patients scheduled for elective Orthopaedic procedures. Methods: We performed an observational, noninterventional study using the demographic characteristics via means chart analysis of in-patients with an elective surgery in a single Swiss Orthopaedic centre. The following variables were collected and analysed: age, gender, BMI, ASA score, rate of vitamin D supplementation before surgery, and serum preoperative levels of vitamin D, albumin, Haemoglobin, calcium, and phosphate. Results: A total of 336 patients were analysed; there were 218 women (64.9%) and 118 men (35.1%). The average age was 59.4 years (17-89 years). The average BMI was 26.8 kg/m2 (17.8-37.6) and the average ASA score was II (I-III). The overall prevalence of vitamin D deficiency was 82.1%, being more common in the male (89.8%) than female patients (77.9%). Patients who received vitamin D supplements before surgery had an average vitamin D level in the normal range. Of the subgroup of 170 patients who were over 60 years of age, 78.8% of the patients were Vitamin D deficient, with deficiency once again being more common in men (93.3%) than in women (92%). Albumin deficiency was documented in 58.9% of the cases. A total of 62.8% of all the female patients were albumin deficient, and 51.7% of all male patients were. Of the subgroup of 170 patients who were over 60 years of age, 71.8% of the patients were albumin deficient, with the deficiency being practically identical in men (71.1%) and women (72%). Conclusions: Despite increased awareness in the medical community, vitamin D and albumin deficiencies remain highly prevalent in elective Orthopaedic patients. Pre/perioperative screening and addressing possible vitamin D and albumin deficiencies are of great importance for good outcomes in Orthopaedic surgery.

Real-life diagnostic and therapeutic approach to CLL: a 2022 update from an expert panel in Tuscany.

A panel of chronic lymphocytic leukemia (CLL) experts from Tuscany propose a real-life diagnostic and therapeutic approach CLL that considers the role of genomic and somatic prognostic factors in risk stratification and treatment decisions. Safety and efficacy of new agents has been demonstrated now not only in clinical trials but also in many real-world series. The BTK inhibitors, ibrutinib and acalabrutinib, and BH3 mimetic venetoclax are now indicated as first-line therapy and chemoimmunotherapy can be spared to the majority of CLL patients, thus preventing unnecessary hematological and non-hematological toxicity and second primary tumors. For treatment, FISH for 17 p and P53 mutational status are essential. IGHV mutation can be done at diagnosis or before treatment. Echography is the gold standard radiological investigation in CLL, at both diagnosis and response evaluation. Chemotherapy is virtually abandoned. Age, genetic risk, and patient comorbidities have to be carefully evaluated for treatment decision. With the availability of different drugs, there is a need for a uniform and shared approach in daily therapeutic choice. The proposed approach is based on current evidence and guidelines as well as results from clinical trials and daily clinical experience.

The Classic Three-Month Post-Operative Adaptation Phase in Foot and Ankle Surgery-An Expert Perspective.

Foot and ankle disorders are a common reason for orthopedic surgical intervention. After surgery, specific precautions such as partial weight bearing or complete unloading, and the use of walking aids, coupled with a period of rest, are usually implemented to ensure the surgical outcome. However, when these aids are discontinued and the patients resume load increase and normal daily activities, they may enter a transitional phase characterized by inflammation, swelling, and pain. We call this phenomenon the "classic three-month post-operative adaptation phase" (POAP). It is essential to differentiate this physiological transition phase from other conditions, such as from the immediate post-surgical inflammation, complex pain regional syndrome, or an infection. The objective of this expert opinion is to describe and raise medical awareness of this evidence-based phenomenon, which we commonly observe in our daily practice.

A Rare Case of Fifth Metatarsophalangeal Joint Subluxation: A Case Report.

Dislocations or subluxations of the metatarsophalangeal joints are rare, and open reduction is necessary in special cases. In this case report, we present the case of a 30-year-old man who had chronic dislocation of the V metatarsophalangeal joint after a motorcycle accident. Stiffening of the joint capsule prevented closed reduction therefore the patient underwent surgery, after performing a Gauthier-type osteotomy the joint was stabilized by k-wire. The patient had an excellent recovery with no new dislocation episodes.

Exploratory Genome-Wide Association Analysis to Identify Pharmacogenetic Determinants of Response to R-CHOP in Diffuse Large B-Cell Lymphoma.

R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 216 any-stage chemonaïve DLBCL patients candidate to R-CHOP were enrolled. The median age of the 185 eligible patients was 59.2 years, 49.7% were women and 45.4% were stage I-II patients. According to the Revised International Prognostic Index (R-IPI), 14.1%, 56.8% and 29.2% were in the very good, good and poor prognosis groups, respectively. Of the patients, 85.9% produced a complete response. Highly significant associations (i.e., p < 5 × 10-8) were found between progression-free survival (PFS) and six SNPs (i.e., rs116665727, rs1607795, rs75614943, rs77241831, rs117500207, rs78466241). Additionally, five SNPs (i.e., rs74832512, rs117500207, rs35789195, rs11721010, rs12356569) were highly associated with overall survival (OS). Wild-type patients showed a prolonged PFS or OS compared with patients carrying deleterious alleles (p < 0.001). No association with the adequate significant threshold was observed between SNPs and the objective response or toxicity. In the future, these SNPs, alone or in combination, after a proper validation in an independent cohort, could contribute to improving the prediction of R-CHOP response.

Hybrid-Total Ankle Arthroplasty (H-TAA) for Failed Talar Component in Mobile-Bearing Total Ankle Arthroplasty.

INTRODUCTION: Revision Total Ankle Arthroplasty (TAA) surgery due to TAA aseptic loosening is increasing. It is possible to exchange the talar component and inlay to another system for isolated talar component loosening in a primary mobile-bearing TAA: Hybrid-Total Ankle Arthroplasty (H-TAA). The purpose of this study was to analyze the results of the revision surgery of an isolated aseptic talar component loosening in a mobile-bearing three-component TAA with a H-TAA solution. METHODS: In this prospective case study, nine patients (six women, three men; mean age 59.8 years; range 41-80 years) with symptomatic isolated aseptic loosening of the talar component of a mobile-bearing TAA were treated with an isolated talar component and inlay substitution. In all nine cases, a hybrid TAA revision surgery was performed by implanting a VANTAGE TAA talar and insert component (Flatcut talar component: six cases, standard talar component: three cases). The patients were reviewed with the pain score (VAS Pain Score 0-10), Dorsiflexion/Plantarflexion (DF/PF) Range of Motion (ROM; degrees), the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle/Hindfoot Score (0-100 points), Sports Frequency Score (Level 0-4), and subjective Patients' Satisfaction Score (0-10 points). RESULTS: The average Pain score improved significantly from preoperative 6.7 points to postoperative 1.1 points (p < 0.001). Average Dorsiflexion/Plantarflexion ROM values increased significantly post-surgery: 21.7° preoperative to 45.6° postoperative (p < 0.001). The postoperative AOFAS scores were significantly greater than the preoperative values: 47.7 points preoperative, 92.3 points postoperative (p < 0.001). The sports activity improved from preoperative to postoperative where, preoperative, none of the patients were able to perform sports. Postoperative, eight patients were able to be sports-active again. The overall average postoperative level of sports activity was 1.4. The postoperative average patient's satisfaction was 9.3 points. CONCLUSIONS: In painful talar component aseptic loosening of a three-component mobile-bearing TAA, H-TAA is a good surgical solution for reducing pain, restoring ankle function, and improving patients' life quality.

Joint-Preserving Surgery in Varus Ankle Osteoarthritis.

Ankle deformity is a disabling condition especially if concomitant with osteoarthritis (OA). Varus ankle OA is one of the most common ankle OA deformities. This deformity usually leads to unequal load distribution in the ankle joint and decreases joint contact surface area, leading to a progressive degenerative arthritic situation. Varus ankle OA might have multiple causative factors, which might present as a single isolated factor or encompassed together in a single patient. The etiologies can be classified as post-traumatic (e.g., after fractures and lateral ligament instability), degenerative, systemic, neuromuscular, congenital, and others. Treatment options are determined by the degree of the deformity and analyzing the pathology, which range from the conservative treatments up to surgical interventions. Surgical treatment of the varus ankle OA can be classified into two categories, joint-preserving surgery (JPS) and joint-sacrificing surgery (JSS) as total ankle arthroplasty and ankle arthrodesis. JPS is a valuable treatment option in varus ankle OA, which should not be neglected since it has showed a promising result, optimizing biomechanics and improving the survivorship of the ankle joint.

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study.

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505.

Ibrutinib in patients with relapsed/refractory mantle cell lymphoma: a real-life, retrospective, multicenter trial on behalf of the "RTL" (regional Tuscan lymphoma network).

BACKGROUND: Relapsed or refractory (R/R) mantle-cell lymphoma (MCL) patients have a poor prognosis and their management is challenging, in absence of a golden standard as salvage treatment. Bruton's tyrosine kinase inhibitor ibrutinib represents an effective treatment for R/R MCL patients. We investigated ibrutinib efficacy and safety in daily clinical practice, together with factors that could predict disease outcome. PATIENTS AND METHODS: We retrospectively analyzed 69 consecutive R/R MCL patients managed in 10 Tuscan onco-hematological centers. The treatment regimen consisted of oral, continuous, single-agent ibrutinib, maximum dosage of 560 mg once per day, until disease progression. RESULTS: Overall response rate was 62.3%, with a CR rate of 39.1%. After a median follow-up of 15.6 months, 40/69 patients (58%) were alive, the main cause of death was progressive disease (PD, 22/69 cases, 31.9%). Median progression-free survival (PFS) and overall survival (OS) were 17 and 34.8 months. Inferior PFS was associated with >1 prior line of therapy and B symptoms. Ibrutinib refractoriness was associated with inferior OS, median OS after ibrutinib failure was only 5 months. DISCUSSION AND CONCLUSION: In this real-life setting ibrutinib treatment prolonged survival in R/R MCL patients, without unexpected adverse events. Patients receiving ibrutinib as 2nd line regimen had the most favorable outcome.

Assigning Rated Items to Locations in Non-List Display Layouts.

One of the most common ways in which results are displayed by an information retrieval system is in the form of a list, in which the most relevant results appear in the first positions. Today's large screens, however, allow one to create more complex displays of results, especially in cases such as image retrieval, in which each unit returned is fairly compact. For these layouts the simple list model is no longer valid, since the relations between the slots in which the results are placed do not form a sequence, that is, the relation among them is no longer that of a total order. In this paper we model these layouts as partial orders and show that a "stalwart display" property (a layout in which items' relevance is unambiguously conveyed by their display position) can be obtained only in the case of lists. For the other layouts, we define two classes of representation functions: "safe" functions (which display results without adding spurious structure) and "rich" functions (which do not drop any structure from the result set), as well as an algorithm to optimally display fully ordered result sets in arbitrary display layouts.

Cardiovascular events and intensity of treatment in polycythemia vera.

BACKGROUND: Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial. METHODS: We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed. RESULTS: After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the high-hematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P=0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P=0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events. CONCLUSIONS: In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT01645124, and EudraCT number, 2007-006694-91.).

Implications of a positive sentinel node in oral squamous cell carcinoma.

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. RESULTS: A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. CONCLUSIONS: The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans.

Darbepoetin alpha in the treatment of cancer chemotherapy-induced anemia.

Anemia is a common, but underestimated and undertreated, complication of patients with cancer receiving chemo- or radiotherapy, and negatively affects their quality of life (QoL). Erythropoietic proteins (EPS) offer an effective treatment of cancer anemia and ameliorate QoL, although their use requires the correct targeting of hemoglobin increase to avoid thromboembolic complications. Currently the effort is focused on offering patients this effective treatment with reduced frequency of administration. Higher weekly single doses of recombinant human Epo (rHuEpo) either alpha or beta, instead of three times per week, have been proposed for the treatment. The pharmacokinetic and pharmacodynamic characteristics of the hyperglycosylated protein darbepoetin alpha permit even longer inter vals between administrations. Every other week or every three weeks schedules have shown results (erythropoietic response, reduction of transfusion requirements, and improvement of QoL) comparable with those of weekly rHuEpo.

ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgV(H) mutations.

BACKGROUND: Expression of T cell specific zeta-associated protein 70 (ZAP-70) by B-cell chronic lymphocytic leukemia (B-CLL) cells, as investigated by flow cytometry, has both prognostic relevance and predictive power as surrogate for immunoglobulin heavy chain variable region (IgV(H)) mutations, although a standardization of the cytometric protocol is still lacking. METHODS: Flow cytometric analyses for ZAP-70 were performed in peripheral blood samples from 145 B-CLL (124 with IgV(H) mutations) by a standard three-color protocol. Identification of ZAP-70(+) cell population was based on an external negative control, i.e., the isotypic control (ISO method) or an internal positive control, i.e., the population of residual normal T/NK cells (TNK method). A comparison between these two approaches was performed. RESULTS: While 86/145 cases were concordant as for ZAP-70 expression according to the two methods (ISO(+)TNK(+) or ISO(-)TNK(-)), 59/145 cases had discordant ZAP-70 expression, mainly (56/59) showing a ISO(+)TNK(-) profile. These latter cases express higher levels of ZAP-70 in their normal T cell component. Moreover, discordant ISO(+)TNK(-) cases had a IgV(H) gene mutation profile similar to that of concordantly positive cases and different from ZAP-70 concordantly negative B-CLL. CONCLUSION: Analysis of ZAP-70 expression by B-CLL cells by using the ISO method allows to overcome the variability in the expression of ZAP-70 by residual T cells and yields a better correlation with IgV(H) gene mutations. A receiver operating characteristic analysis suggests to employ a higher cut-off than the commonly used 20%. A parallel evaluation of the prognostic value of ZAP-70 expression, as determined according to the ISO and TNK methods, is still needed.

Generalized B-cell non Hodgkin's lymphoma in association with leukocytoclastic vasculitis and disseminated intravascular coagulation.

A 66-year-old woman was referred a 4-month history of asthenia, weight loss, productive cough, increasing dyspnea, epigastric pain, and night sweats. A B-cell non-Hodgkin lymphoma was discovered in association with a severe leukocytoclastic vasculitis and disseminated intravascular coagulation. The patient was treated successfully with the combination of cyclophosphamide, vincristine, prednisone, and rituximab.

Biomedical informatics research network: building a national collaboratory to hasten the derivation of new understanding and treatment of disease.

Through support from the National Institutes of Health's National Center for Research Resources, the Biomedical Informatics Research Network (BIRN) is pioneering the use of advanced cyberinfrastructure for medical research. By synchronizing developments in advanced wide area networking, distributed computing, distributed database federation, and other emerging capabilities of e-science, the BIRN has created a collaborative environment that is paving the way for biomedical research and clinical information management. The BIRN Coordinating Center (BIRN-CC) is orchestrating the development and deployment of key infrastructure components for immediate and long-range support of biomedical and clinical research being pursued by domain scientists in three neuroimaging test beds.

The cell-centered database: a database for multiscale structural and protein localization data from light and electron microscopy.

The creation of structured shared data repositories for molecular data in the form of web-accessible databases like GenBank has been a driving force behind the genomic revolution. These resources serve not only to organize and manage molecular data being created by researchers around the globe, but also provide the starting point for data mining operations to uncover interesting information present in the large amount of sequence and structural data. To realize the full impact of the genomic and proteomic efforts of the last decade, similar resources are needed for structural and biochemical complexity in biological systems beyond the molecular level, where proteins and macromolecular complexes are situated within their cellular and tissue environments. In this review, we discuss our efforts in the development of neuroinformatics resources for managing and mining cell level imaging data derived from light and electron microscopy. We describe the main features of our web-accessible database, the Cell Centered Database (CCDB; http://ncmir.ucsd.edu/CCDB/), designed for structural and protein localization information at scales ranging from large expanses of tissue to cellular microdomains with their associated macromolecular constituents. The CCDB was created to make 3D microscopic imaging data available to the scientific community and to serve as a resource for investigating structural and macromolecular complexity of cells and tissues, particularly in the rodent nervous system.