Herpesviral encephalitis associated with bortezomib use in a patient with multiple myeloma and associated light-chain amyloidosis.

INTRODUCTION: Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce. CASE REPORT: A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid. MANAGEMENT & OUTCOME: The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Spatial and Temporal Entropies in the Spanish Football League: A Network Science Perspective.

We quantified the spatial and temporal entropy related to football teams and their players by means of a pass-based interaction. First, we calculated the spatial entropy associated to the positions of all passes made by a football team during a match, obtaining a spatial entropy ranking of Spanish teams during the 2017/2018 season. Second, we investigated how the player's average location in the field is related to the amount of entropy of his passes. Next, we constructed the temporal passing networks of each team and computed the deviation of their network parameters along the match. For each network parameter, we obtained the permutation entropy and the statistical complexity of its temporal fluctuations. Finally, we investigated how the permutation entropy (and statistical complexity) of the network parameters was related to the total number of passes made by a football team. Our results show that (i) spatial entropy changes according to the position of players in the field, and (ii) the organization of passing networks change during a match and its evolution can be captured measuring the permutation entropy and statistical complexity of the network parameters, allowing to identify what parameters evolve more randomly.

Survival analysis of transplant-eligible newly-diagnosed multiple myeloma patients harboring t(4;14), t(14;16), and/or del(17p) in the real-world setting.

Cytogenetic abnormalities (CA) such as t(4;14), t(14;16), and del(17p), are associated with a poor prognosis in Multiple Myeloma (MM) patients. However, there is scarce information regarding the Latin-American population. This study aims to analyze the impact of t(4;14), t(14;16), and del(17p) on the progression-free survival (PFS) and overall survival (OS) of transplant-eligible newly-diagnosed MM (NDMM) patients in Latin America. Retrospective survival analysis based on the Grupo de Estudio Latinoamericano de MM (GELAMM) registry, including all adult patients with NDMM harboring CA t(4;14), t(14;16), and/or del(17p). Fifty-nine patients were included; the median age was 57 years, 55.9% males, 22% ISS-I, 25.4% ISS-II, and 47.5% ISS-III. The majority (89.8%) had one alteration, whereas 10.2% had del(17p) and t(4;14). The frequencies of CA were del(17p) in 61.0%, t(4;14) in 25.4%, and t(14;16) in 3,4%. Autologous stem cell transplantation was performed in 36 cases, 20 patients did not use this consolidative strategy, and this data was missed in three cases. Five-year OS for the entire cohort was 60.8% and 5-year PFS was 28.1%. Bortezomib-based induction regimen (BBR) (p=0.029), consolidation with ASCT (p<0.001), and maintenance therapy (p=0.004) were associated with an improved 5-year OS. In the multivariate analysis, ASCT was the only variable with a positive impact on OS (HR 0.11, 95% CI 0.033 to 0.34, p<0.001). The median PFS presented a non-statistically significant benefit in BBR, ASCT, and maintenance therapy groups. BBR induction, ASCT, and maintenance therapy were associated with improved OS in high-risk NDMM patients.

Epidemiology and risk factors for the development of infectious complications in newly diagnosed multiple myeloma: a multicenter prospective cohort study in Uruguay.

INTRODUCTION: Infections represent a significant cause of morbidity and mortality in patients with multiple myeloma (MM). In Latin America, data on infectious complications in newly diagnosed MM (NDMM) patients are limited. METHODS: We conducted a multicenter, prospective cohort study of patients with NDMM in Uruguay between June 2019 and December 2020. Patients with active disease, on active therapy and who provided written informed consent were included. Elegible patients were followed for 6 months from the time of diagnosis and before proceeding to autologous stem cell transplantation or until death, whichever occurred first. Our primary endpoint was the number of infectious events that required hospitalization for ≥ 24 h. MAIN RESULTS: Of 124 patients with NDMM, 54 (43.5 %) had infectious complications (74 infectious events), the majority (74.3 %) within the first 3 months from diagnosis. The most common sites of infection were urinary (39.2 %) and respiratory tracts (33.8 %). The microbial agent was identified in 60.8 % of patients with Gram-negative bacteria (71.4 %) as the most common pathogen. Viral and fungal infections were infrequent. In the multivariable analysis, the Eastern Cooperative Oncology Group (ECOG) performance status was ≥ 2 (odds ratio [OR], 2.16; 95 % confidence interval [95 %CI], 1.23 - 3.79; p = 0.008) and creatinine ≥ 2 mg/dl (OR, 2.33; 95 %CI, 1.33 - 4.07; p = 0.003) were independent factors associated with bacterial infections. At 6 months, 14 patients (11.3 %) had died, 50 % related to infectious complications. CONCLUSION: Bacterial infections are a substantial cause of hospital admissions and early death in patients with NDMM. Antibiotic prophylaxis should be considered to reduce infectious complications in patients with MM.

Survival Analysis of Newly Diagnosed Multiple Myeloma Patients after Frontline Autologous Stem Cell Transplantation in a Real-Life Setting.

INTRODUCTION: Autologous stem cell transplantation (ASCT) is the standard consolidation option for transplant-eligible patients with multiple myeloma (MM). The aim of this study is to report the overall survival (OS) and progression-free survival (PFS) outcomes after frontline ASCT in newly-diagnosed MM (NDMM) patients in a real-world setting. METHODS: We conducted a retrospective, survival analysis of all NDMM patients included in the MM Uruguayan Registry. RESULTS: We included 151 NDMM patients treated with induction therapy followed by high-dose melphalan and ASCT as consolidation. The median age at diagnosis was 59 years, and the international staging system (ISS) risk groups were ISS-III 32.9%, ISS-II 37.8%, and ISS-I 29.4%. Frontline induction regimens included bortezomib in 61.6% of cases, and maintenance therapy was used in 63.9% of reported cases. With a median follow-up of 42 months, the 36-month OS and PFS for the whole group were 82.4% (95% CI 75.9% to 89.4%) and 63.8% (95% CI 55.6% to 73.3%), respectively, median OS of 98 months and median PFS of 47 months. The 100-month OS and PFS for the entire group were 48.0% (95% CI 34.9% to 66.0%) and 17.3% (95% CI 8.4% to 35.8%), respectively. CONCLUSION: ASCT is a feasible, safe, and potent strategy that provides a prolonged median OS and PFS in NDMM patients. This approach can be implemented in low-income countries.

Young age and autologous stem cell transplantation are associated with improved survival in newly diagnosed multiple myeloma.

BACKGROUND: Multiple myeloma is a disease of the elderly. However, 40% of patients are diagnosed before 65 years old. Outcomes regarding age as a prognostic factor in MM are heterogeneous. METHOD: We retrospectively analyzed clinical characteristics, response to treatment and survival of 282 patients with active newly-diagnosed multiple myeloma, comparing results between patients younger and older than 65 years. MAIN RESULTS: The frequency of multiple myeloma in those younger than 66 years was 53.2%. Younger patients presented with a more aggressive disease, more advanced Durie-Salmon stage (85.3% vs 73.5%; p=0.013), extramedullary disease (12.7% vs 0%; p<0.001), osteolytic lesions (78.7% vs 57.6%; p<0.001) and bone plasmacytoma (25.3% vs 11.4%; p=0.003). In spite of this, the overall response rate was similar between groups (80.6% vs 81.4%; p=0.866). The overall survival was significantly longer in young patients (median, 65 months vs 41 months; p=0.001) and higher in those who received autologous hematopoietic stem cell transplantation. The main cause of death was disease progression in both groups. Multivariable analysis revealed that creatinine ≥2mg/dl, extramedullary disease, ≤very good partial remission and non-autologous hematopoietic stem cell transplantation are independent risk factors for shorter survival. CONCLUSION: Although multiple myeloma patients younger than 66 years of age have an aggressive presentation, this did not translate into an inferior overall survival, particularly in those undergoing autologous hematopoietic stem cell transplantation.

The mortality burden of hematological malignancies in Ecuador.

BACKGROUND: The Hematological neoplasms (HN) are a heterogeneous group of cancers that originated in the hematopoietic or lymphoid tissues. There is reduced information published regarding HN mortality in Ecuador. This study aims to present the crude and age-specific mortality rates for HN in the Ecuadorian population. METHODS: We performed a cross-sectional study through the national database of defunctions published by the Ecuadorian National Institute of Statistics and Census, 2019. We used the ICD-10 codes to classify the HN. RESULTS: During 2019, 1462 deaths were reported, 53.83% were males, 87.96% of mestizo ethnicity, and 78.32% residents in urban areas. The median age was 62 years, with an interquartile range of 34.The crude mortality rate obtained was 8.49 per 100000 inhabitants, and the higher age-specific mortality rates was 43.29 per 100000 inhabitants aged ≥ 60 years, contrasting with the 2.63 per 100000 inhabitants in people aged < 20 years. Considering each ICD-10 group, we found the following rates by 100000 inhabitants; C85 2.04, C91 1.92, C92 1.46, C90 1.11, C83 0.70, C95 0.48, C81 0.38, C84 0.16, C82 0.10, C96 0.05, C93 0.04, C86 and C94 0.02, and C88 0.01. CONCLUSION: In Ecuador, during 2019, approximately eight people died due to HN by 100000 inhabitants, affecting mainly people aged ≥ 60 years. The most frequent neoplasms were Non-Hodgkin lymphomas, similar to other reports globally. These results should be analyzed considering some deficiencies in the Ecuadorian health system and the national registry. Therefore, we suggest conducting more studies regarding HN.

Comparative survival analysis using the International Stratification Score (ISS) in newly-diagnosed multiple myeloma in the Uruguayan population.

BACKGROUND AND AIMS: Multiple myeloma is a frequent hematologic malignancy, in which the International Stratification Score (ISS) is widely used to estimate the overall survival. However, there are no studies in Latin America evaluating its performance. This study aims to describe the ISS performance in the overall survival estimation for newly diagnosed multiple myeloma patients in Uruguay. METHODS: This is a retrospective registry-based survival analysis through the Grupo Uruguayo de Mieloma Múltiple (GUMMA) database, including newly diagnosed multiple myeloma patients from January 2001 until May 2019. RESULTS: 249 patients were included, 51.81% males and an average age of 63.49 years. According to ISS and Durie-Salmon score (DSS), 47.79% and 82.3% were ISS III and DSS III, respectively. Also, 32.3% were DSS B. Auto hematopoietic stem cell transplantation was performed in 31.73% of patients, and bortezomib was used in 44.18% as frontline therapy. The overall survival was 80% for ISS1, 64.9% ISS2, and 48.6% ISS3 (Log-Rank; p <0.01). The average overall survival was 116.5 months for ISS 1, 77.6 months for ISS 2, and 57.8 months for ISS 3. The hazard ratio between ISS II and ISS I was 2.42 (95% CI 1.10-5.33; p<0.05), and 3.94 (95% CI 1.88-8.26; p<0.05) between ISS III and ISS II. CONCLUSION: The ISS staging system allows an adequate stratification of patients according to overall survival in the real-practice setting. However, considering the relevance of the new cytogenetic advances, it is necessary to increase the availability and quality of iFISH in Latin America.

Distance Between Players During a Soccer Match: The Influence of Player Position.

In this study, we analyse the proximity between professional players during a soccer match. Specifically, we are concerned about the time a player remains at a distance to a rival that is closer than 2 m, which has a series of consequences, from the risk of contagion during a soccer match to the understanding of the tactical performance of players during the attacking/defensive phases. Departing from a dataset containing the Euclidean positions of all players during 60 matches of the Spanish national league (30 from LaLiga Santander and 30 from LaLiga Smartbank, respectively, the first and second divisions), we analysed 1,670 participations of elite soccer players. Our results show a high heterogeneity of both the player-player interaction time (from 0 to 14 min) and the aggregated time with all opponents (from <1 to 44 min). Furthermore, when the player position is taken into account, we observe that goalkeepers are the players with the lowest exposure (lower than 1 min), while forwards are the players with the highest values of the accumulated time (~21 min). In this regard, defender-forward interactions are the most frequent. To the best of our knowledge, this is the largest dataset describing the proximity between soccer players. Therefore, we believe these results may be crucial to the development of epidemiological models aiming the predict the risk of contagion between players and, furthermore, to understand better the statistics of all actions that involve proximity between players.

A new prognostic pelvic injury outcome score.

Aim To propose a new prognostic classification system for pelvic injuries based on a new detailed and all-encompassing evaluation of the injury pelvic outcome score and to check the prognostic value of this classification and evaluate its reliability and reproducibility. Methods From January 2017 to June 2020 from 156 pelvic fractures treated at our hospitals, 98 patients with pelvic fractures were recruited according to inclusion and exclusion criteria. All patients compiled three scores (New Score System, Majeed Score, SF-12) sessions two times during the hospital stay to evaluate the endpoint before the trauma and two years after the trauma. All patients carried out three tests independently. The evaluation of three scores included a pelvic and general complication after the surgery, the times needed to compile three score system. For reliability of the new score systems we evaluated the inter-observer or intraobserver agreement, the prediction strength of each score, and a prognostic value. Results A total of 98 patients were enrolled (74 were males and 24 females) with mean age of 43.6 (±18.6) (range 16-75) years. Tau B Kendall value was 0.827 for the new score system, 0.673 for the Majeed score, 0.746 for SF-12, there was p<0.05 for the new score system. Conclusion The new score system is prognostic, reliable, reproducible and can become a useful instrument to adequately correlate the long-term outcomes of pelvic injury fractures. Also, it provides a better evaluation of pain, work, sexual possibilities and satisfaction, balance-sitting-walking and psychological status.

The Bisaccia and Meccariello technique in pediatric femoral shaft fractures with intramedullary titanium nail osteosynthesis linked external-fixator (IOLE): validity and reliability.

BACKGROUND: Over the last 20 years, the incidence of pediatric femoral shaft fractures was increased, due to changes in the children's daily activities. The healing times are different according to the chosen treatment and to other factors such as age, type of fracture, the involvement of the soft tissues, and concomitance with other injuries. The Bisaccia and Meccariello technique ( Intramedullary titanium nail Osteosynthesis Linked External-fixator -IOLE) was born to prevent rotationally and lengthening malunion or nonunion in the treatment of pediatric femoral shaft fractures. The aim or the objective of this paper is to compare the IOLE with the two most used methods for the treatment of femoral fractures in children. METHODS: From 2000 to 2016, 58 pediatric patients with femoral shaft fractures were surgically treated and enrolled in the study. The ranged age of the patients was between 3 and 15 years. Twenty-two patients were treated with endomedullary titanium nails (TEN), 16 with external axial or modular external fixators and 14 patients treated with IOLE technique. The IOLE technique is the hybridization of titanium intramedullary nails with a modular external fixator. It is divided into three phases, the first revenue given the length of the femur with the external fixator; the second, the rotations are dominated by the elastic nails; and the third finally they are hybridized on the external fixator. Comparing the three groups, radiographic images were taken to assess fracture reduction and consolidation.  RESULTS: At the final follow-up, there were no differences between three groups in terms of significant rotation defects, angulation, growth, and/or nonunion but there was a statistical in IOLE groups for the early weight-bearing. CONCLUSIONS: The Bisaccia- Meccariello technique (IOLE) showed to lead to healing the pediatric femoral shaft fracture of the femur but allows an early weight-bearing to these patients and normal life like that.

Pathological Clavicle Fracture as the First Symptom of Lung Cancer.

INTRODUCTION: Pain around the shoulder is very common. The most frequent causes of shoulder pain without traumatic even are rotator cuff diseases, shoulder, and sternoclavicular arthritis, other causes are neoplastic pathology, but lung cancer metastasis has never been described. CASE REPORT: We describe a rare case of pathological clavicle fracture as the cause of atraumatic shoulder pain, as the first case of lung cancer, and discuss the different cause of shoulder pain. CONCLUSION: Pathological clavicular fracture is a very rare disease and symptom of lung cancer but should be in the differential diagnosis in patients with focal pain without traumatic event and abnormal radiographic studies.

Surgical treatment of multifragmentary segmental femur shaft fractures with ORIF and bone graft versus MIPO: a prospective control-group study.

Aim Multifragmentary segmental femoral shaft fracture is a high energy injury frequently associated with life-threatening conditions. The aim of this study was to compare the use of bio metallic open reduction internal fixation (ORIF) (plate with allograft bone strut) with minimally invasive plate osteosynthesis (MIPO) fixation for the treatment of multi-segmental femoral shaft fracture in terms of outcomes, bone healing and complications. Methods Forty patients with segmental femoral shaft fractures were included and divided into two groups: 20 patients treated with ORIF+, 20 with MIPO. All fractures were classified according to AO (Arbeitsgemeinschaft für Osteosynthesefragen) and Winquist and Hansen Classification. Evaluation criteria were: duration of follow up and surgery, Non-Union Scoring System, Pain Visual Analogic Scale (VAS), objective quality of life and hip function, subjective quality of life and knee function, quality of life the Short Form-12 Survey Questionnaires (SF-12), bone healing and femoral alignment (radiographs), Radiographic Union Score for Hip (RUSH). Results Better results of ORIF in terms of complication rate, RUSH, VAS, regression between RUSH and VAS, average correlation clinical-radiographic results and patients' outcomes (Cohen k) were obtained, and similar results for the length of follow up, surgery duration, perioperative blood transfusion, wound healing. No statistical difference for Harris Hip Score (HHS), Knee Society Score (KSS), quality of life (SF-12). Conclusions The ORIF and bone strut allograft technique had better results compared to the MIPO technique with regards to complication rate, RUSH, VAS, regression between RUSH and VAS, and average correlation clinical-radiographic results and patients' outcomes (Cohen k) in the surgical treatment of multifragmentary segmental femoral shaft fractures.

A Lasso-Loop Traction Technique for Arthroscopic Superior Capsular Reconstruction.

Irreparable rotator cuff tears (RCTs) cause shoulder pain and disfunction. Management of RCT patients has classically been difficult due to few treatment options. Since Mihata et al. in 2013 introduced the superior capsular reconstruction (SCR) technique as a treatment option, it has become widespread among surgeons, especially for young active patients in whom reverse shoulder arthroplasty is not recommended. With SCR, a reduced humeral head can be maintained and superior displacement is avoided, improving shoulder pain and restoring active shoulder motion. A variety of grafts may be used, but the surgery can be technically complicated. An arthroscopic lasso-loop traction technique for SCR is described here, which simplifies graft shoulder reduction by traction from the anteromedial and posteromedial portals.

Strut graft vs. traditional plating in the management of periprosthetic humeral fractures: a multicentric cohort study.

Aim The gradual increase in shoulder implants in active elderly patients has appeared in a parallel increase in periprosthetic humeral fractures. The aim of this study was to investigate the advantages of using strut grafting with plate fixation during periprosthetic humerus fractures. Methods Thirty patients diagnosed with periprosthetic humeral fracture were divided into two groups. The first group of 15 patients (PS) underwent plate, ring, screws and strut allografts. The second group with resting 15 patients (PWS) was treated with only plate and screws. The criteria to evaluate the groups during followup were the Constant Shoulder Score (CSS) and Oxford Shoulder Score (OSS); the bone healing was measured by X-rays, controls measured by radiographic union score (RUS), and complications. The follow up was terminated at 12nd month in both groups. Results The difference between the two groups in all parameters was not significant. However, all patients gained adequate shoulder motor skills for normal daily living activities. All fractures were healed. Only two complications were registered, and blood loss was minimal. Conclusion We believe a revision to reverse shoulder prosthesis with a long-stem implant with or without cortical strut allograft augmentation to be safe and appropriate in the management of these complex injuries, though technically challenging, and having good results for normal activities daily life.

Tibial diaphyseal fractures in children: indications and limitations of the treatment with monolateral and hybrid external fixator.

Aim To report our indications and limitations about the use of external fixation in children. Methods It was retrospectively reviewed all tibial fractures treated with monolateral and hybrid external fixator, at our three Centres. It was included 32 fractures which did not show an acceptable reduction after an attempt under anaesthesia. The exclusion criteria were: open fractures, children with previous fractures of the lower limbs, with skeletal congenital diseases, fractures involving the physis and with neurovascular involvement. All fractures were classified according to the AO (Arbeitsgemeinschaft für Osteosynthesefragen) classification. An outcome was evaluated according to the time needed to obtain radiographic bone healing, the range of motion (ROM) of the ankle, the asymmetry of the lower limbs, the malunion, and complications. Results The average time of consolidation was 10.66 weeks (6-17 weeks). There were no cases of deep infection, but only seven cases of superficial pin infections. No patients reported loss of ROM of the knee or ankle. We had zero cases of residual angle greater than 5°, and in all cases the difference in length between the limbs was <1 cm. Conclusion The external fixation is a viable technique in the treatment of tibial fractures in children. Therefore, the external fixation, both monolateral and hybrid, should be considered a viable treatment for this type of fracture.

Feasibility and value of non-locking retrograde nail vs. locking retrograde nail in fixation of distal third femoral shaft fractures: radiographic, bone densitometry and clinical outcome assessments.

Aim Distal femoral shaft fractures are characterized by increasing incidence and complexity and are still considered a challenging problem. No consensus on best surgical option has been achieved. The aim of this study is to investigate mineral bone densitometry, radiographic and clinical outcomes of locking retrograde intramedullary nailing (LRN) and non-locking retrograde intramedullary nailing (NLRN) regarding surgical treatment of distal femoral shaft fractures in adults based on the hypothesis that there is no statistical difference among the results of both surgical options. Methods Retrospective study: 30 patients divided into 2 groups (Group 1 LRN, Group 2 NLRN). Average age was 42.67±18.32 for Group 1 and 44.27±15.11 for Group 2 (range of age 18-65 for both groups). Gender ratio (male:female) was 2.75 (11:4) for both groups. AO Classification, Non Union Scoring System (NUSS) and Radiographic Union Score Hip (RUSH), Visual Analogic Score (VAS), Dexa scans, plain radiographs were used. Evaluation endpoint: 12 months after surgery. Results No statistical difference was obtained in terms of surgery time, transfusions or wound healing. There were similar results regarding average time of bone healing, RUSH scores, VAS, regression between RUSH and VAS, average correlation clinical-radiographic results and patients outcomes. Only one patient of LRN group had reduction of mineral bone densitometry values. Conclusion No statistical difference in terms of radiographic, bone densitometry and clinical outcomes among LNR and NLNR for the treatment of distal femur fractures was found. The presence of no statistical difference regarding radiological findings is the main factor supporting our hypothesis given their strong objectivity.

Supraclavicular excision of a cervical rib for treatment of thoracic outlet syndrome.

Cervical rib resection through a supraclavicular approach is a safe and feasible treatment for patients suffering from thoracic outlet syndrome caused by the presence of a cervical rib or by an anomalous first rib. This video tutorial illustrates the technical aspects of this procedure.