Floating Knee Arthrodesis After Prosthetic Knee Infection: A Report of 48 Cases.

BACKGROUND: Knee arthrodesis is a means of avoiding above-knee amputation after a prosthetic joint infection (PJI). The objective of this study was to analyze the results of floating knee arthrodesis in patients who had a history of aprosthetic knee infection. The analysis consisted of determining reinfection rates, functional results, and the survival of arthrodesis. METHODS: There were 48 patients who underwent a cemented floating knee arthrodesis in cases of PJI retrospectively included in the study, having been operated on between 2012 and 2020. In addition to being evaluated clinically, analytically, and radiographically, the patients were assessed functionally by means of a newly-created scale. RESULTS: At a mean follow-up of 4 years (1 year to 9 years), 7 patients suffered reinfection (14.6%). The recurrence of infection was not observed to be significantly affected by sex (P = .16), age(P = .09), or the type of surgery previously undergone (P = .18), nor was the McPherson Host Grade (P = .4) observed to have a significant effect. Patients who had a McPherson Limb Grade 3 were more likely to suffer reinfection than those with a McPherson Limb Grade 2 (P = .034). There were 26 patients (54%)fully evaluated and scored on the Knee Arthrodesis Functional Scale(BAOR). For 11 patients (42%), the results were evaluated as excellent, for 11 (42%) acceptable, for 3 (12%) low, and for 1(4%) poor. CONCLUSION: The arthrodesis nail is an effective and safe procedure for patients who have a recurrent PJI, providing an effective alternative when the criteria for a new revision total knee arthroplasty are not met.

[Epidemiological characteristics of reinfection of 2019-nCoV and influencing factors in Ningbo].

Objective: To analyze the epidemiological characteristics of reinfection of 2019-nCoV and influencing factors, and provide evidence for effective prevention and control of COVID-19 epidemic. Methods: The incidence data of COVID-19 in Ningbo from January 1, 2020 to November 30, 2022 were collected from the infectious disease surveillance system of Chinese information system for disease control and prevention. The incidence of reinfection of 2019-nCoV was investigated by using questionnaire. logistic regression analysis was used to analyze the influences of gender, age, time interval from the first infection, history of underlying disease, 2019-nCoV vaccination dose and disease severity on the reinfection. Results: A total of 897 previous 2019-nCoV infection cases were investigated, of which 115 experienced the reinfection of 2019-nCoV, the reinfection rate was 12.82%. The interval between the two infections M(Q1, Q3) was 1 052 (504, 1 056) days. Univariate analysis showed that age, 2019-nCoV vaccination dose, history of underlying disease, type of 2019-nCoV variant causing the first infection, time interval from the first infection and severity of the first infection were associated with the reinfection rate (all P<0.05). Multivariate logistic regression analysis showed that the risk for reinfection in age group 30- years was higher than that in age group ≥60 years (OR=2.10, 95%CI: 1.11-3.97). No reinfection occurred in those with time interval from the first infection of <6 months, and the risk for reinfection was higher in those with the time interval of ≥12 months than in those with the time interval of 6- months (OR=6.68, 95%CI: 3.46-12.90). The risk for reinfection was higher in the common or mild cases than in the asymptomatic cases (OR=2.64, 95%CI: 1.18-5.88; OR=2.79, 95%CI: 1.27-6.11). Conclusion: The time interval from the first infection was an important influencing factor for the reinfection of 2019-nCoV, and the probability of the reinfection within 6 months was low.

1.5-Stage Versus 2-Stage Exchange Total Hip Arthroplasty for Chronic Periprosthetic Joint Infections: A Comparison of Survivorships, Reinfections, and Patient-Reported Outcomes.

BACKGROUND: Management of periprosthetic joint infection after total hip arthroplasty (THA) has traditionally consisted of a 2-stage approach. However, 1.5-stage exchange has garnered recent interest. We compared 1.5-stage to 2-stage exchange recipients. Specifically, we assessed (1) infection-free survivorship and risk factors for reinfection; (2) 2-year surgical/medical outcomes (eg, reoperations, readmissions); (3) Hip Disability and Osteoarthritis Outcome Scores for Joint Replacement (HOOS-JR); and (4) radiographic outcomes (ie, progressive radiolucent lines, subsidences, and failures). METHODS: We reviewed a consecutive series of 1.5-stage or planned 2-stage THAs. A total of 123 hips were included (1.5-stage: n = 54; 2-stage: n = 69) with mean clinical follow-up of 2.5 years (up to 8 years). Bivariate analyses assessed incidences of medical and surgical outcomes. Additionally, HOOS-JR scores and radiographs were evaluated. RESULTS: The 1.5-stage exchange had 11% greater infection-free survivorship at final follow-up compared to 2 stages (94% versus 83%, P = .048). Morbid obesity was the only independent risk factor demonstrating increased reinfection among both cohorts. No differences in surgical/medical outcomes were observed between groups (P = .730). HOOS-JR scores improved markedly for both cohorts (1.5-stage difference = 44.3, 2-stage difference = 32.5; P < .001). A total of 82% of 1.5-stage patients did not demonstrate progressive femoral or acetabular radiolucencies, while 94% of 2-stage recipients did not have femoral radiolucencies and 90% did not have acetabular radiolucencies. CONCLUSION: The 1.5-stage exchange appeared to be an acceptable treatment alternative for periprosthetic joint infections after THAs with noninferior infection eradication. Therefore, this procedure should be considered by joint surgeons for treatment of periprosthetic hip infections.

Outcomes of chlorhexidine lavage without capsulectomy versus complete capsulectomy after lead extraction for the treatment of cardiac implantable electronic device infection.

INTRODUCTION: Capsulectomy is recommended in patients with cardiac implantable electronic device (CIED) infection after transvenous lead extraction (TLE) but is time-consuming and requires extensive tissue debridement. In this study, we describe the outcomes of chlorhexidine gluconate (CHG) lavage in lieu of capsulectomy for the treatment of CIED infections. METHODS: This retrospective study included patients who underwent TLE for CIED-related infections in two institutions in Colombia. In the capsulectomy group, complete capsulectomy was performed after hardware removal. In the CHG group, exhaustive lavage of the generator pocket with 20 cc of CHG at 2% followed by irrigation with approximately 500 cc of normal saline (0.9% sodium chloride) was performed. The primary outcomes included reinfection and hematoma formation in the generator pocket. Secondary outcomes included the occurrence of any adverse reaction to chlorhexidine, the need for reintervention, infection-related mortality, and total procedural time. RESULTS: A total of 102 patients (mean age 67.2 ± 13 years, 32.4% female) underwent CIED extraction with either total capsulectomy (n = 54) or CHG (n = 48) lavage. Hematoma formation was significantly higher in the capsulectomy group versus the CHG group (13% vs. 0%, p = .014), with no significant differences in the reinfection rate. Capsulectomy was associated with longer procedural time (133.7 ± 78.5 vs. 89.9 ± 51.8 min, p = .002). No adverse reactions to CHG were found. Four patients (4.3%) died from worsening sepsis: three in the capsulectomy group and one in the CHG group (p = .346). CONCLUSIONS: In patients with CIED infections, the use of CHG without capsulectomy resulted in a lower risk of hematoma formation and shorter procedural times without an increased risk of reinfection or adverse events associated with CHG use.

Clinical impact of microbiological results in two-stage revision arthroplasty with spacer exchange.

INTRODUCTION: Patients who require a spacer exchange as part of a two-stage procedure for the treatment of periprosthetic hip and knee joint infections (PJI) have high failure rates. Little is known about the clinical impact of microbiological results and changes in the microbiological spectrum and resistance pattern in these patients. MATERIAL AND METHODS: Between 01/2011 and 12/2019, 312 patients underwent a total of 327 two-stage revision arthroplasties at our institution. A spacer exchange was required in 52/312 (16.7%) patients (27 knee/25 hip). Microbiological results, antibiotic resistance patterns, patient's host factors as well as re-revision and re-infection rates at a median follow-up of 47.8 months (range 12.2-116.7 months) were analyzed. A propensity score (PS)-matched analysis of patients who underwent spacer exchange and patients treated with standard two-stage procedure was performed. RESULTS: We found a high number of microbiological spectrum changes in patients with multiple culture positive procedures between explantations and spacer exchanges (10/12 [83.3%]), spacer exchanges and reimplantations (3/4 [75%]) as well as between reimplantations and subsequent re-revision surgeries (5/6 [83.3%]). In 9/52 (17.3%) patients, same microorganisms were detected repeatedly in two different procedures. We observed changes in the antibiotic resistance patterns in 6/9 (66.7%) of these patients. High re-infection rates were found in patients with culture positive reimplantations (10/12 [83.3%]), and low re-infection rates were found in patients with culture negative reimplantations (2/40 [5%]; p < 0.001). Between patients with and without spacer exchange, no differences were found in the re-revision rates (13/52 [25%] with vs. 13/52 [25%] without; p = 1.00) as well as re-infection rates (12/52 [23.1%] with vs. 8/52 [15.4%] without; p = 0.32). CONCLUSIONS: Changes in microbiological spectrum and antibiotic resistance patterns between stages are common in patients who require a spacer exchange. If eradication of the microorganism at reimplantation can be accomplished, comparable re-revision rates to standard two-stage procedures can be achieved.

Reinfection rates after one- and two-stage revision surgery for hip and knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Revisions for periprosthetic joint infection of knee and hip arthroplasty can be performed following one- or two-stage treatment protocols. Current literature is inconclusive whether one protocol is superior to the other, as prior literature reported similar reinfection rates for both treatment options. We aimed to provide a systematic review and meta-analysis of current literature on septic arthroplasty revisions. METHODS: Between April 2015 and December 2020, Medline, Embase, and The Cochrane Library were searched for studies reporting reinfection outcomes in patients treated with one-stage and two-stage knee or hip revision arthroplasty. Two reviewers independently extracted data and disagreements were resolved by a third investigator. We utilized a double arcsine transformation, prior to pooling using a random-effects model. RESULTS: For hip revision arthroplasty, we identified 14 one-stage studies (n = 1237) with a pooled reinfection rate of 5.7% (95% CI 3.7-8.1%), and 46 two-stage studies (n = 5009) with a reinfection rate of 8.4% (95% CI 6.9-9.9%). For knee revision arthroplasty, 6 one-stage studies (n = 527) and 48 two-stage studies (n = 4344) were identified with reinfection rates of 12.7% (7.0-19.7%) and 16.2% (13.7-19.0%), respectively. Overall, reinfection rates did not vary substantially after subgroup analysis. Limitations of our study are the limited amount of one-stage studies that introduce a potential bias. CONCLUSION: The reinfection rates following one- and two-stage hip and knee arthroplasty revisions were similar. Knee reinfection rates have increased compared to the previous analysis. Individual patient characteristics and adequate treatment algorithms are needed for a more individual selection approach, until a randomized trial is performed.

Two-stage exchange for PJI with co-existing cerclages for fracture: higher rates of early re-infections and difficult to treat microbes.

INTRODUCTION: Periprosthetic joint infections (PJI) with osteosynthesis material for contemporaneous fractures are a challenging, yet poorly described condition. This study will analyze PJI with co-existing fractures treated with cerclages and two-stage exchange. MATERIALS AND METHODS: Patients with and without cerclages for coexisting periprosthetic fractures, undergoing two-stage exchange for PJI of hip or knee, between 06/2013 and 02/2016, were compared concerning baseline characteristics and re-infection rate in the course of a 2 year follow-up. All patients were treated with a standardized two-stage protocol. A PJI was defined according to the EBJIS criteria. All foreign material, including cerclages, was sent in for sonication for microbiological analysis. RESULTS: Ninety-six patients treated with two-stage exchange for PJI could be included. Co-existing fractures treated with cerclage were identified in nine patients (9.3%, study group). Diaphyseal femoral simple in five cases (AO2A3) and proximal intertrochanteric in three cases (AO1A3) were the leading fracture locations. In one patient, cerclage implantation was performed prior to prosthesis explantation, in six, during prosthesis explantation, and in two, in the course of prosthesis reimplantation. The study group showed a significantly higher rate of difficult to treat microbes (44.4%; 8.0%; p = .001), Charlson Comorbidity Index (5.4; 3.7; p = .033), relapse infections with the same microbe (22.2%; 1.1%; p = .001), and early-onset infections (< 30 days) (11.1%; 1.1%; p = .046), than the comparison two-stage exchange group without fractures. In contrast, age (72.5 study group; 68.2 comparison group; p = .224), rate of revisions for PJI in the past (55.5%; 51.7%; p = .827), and total re-infection rate (22.2%; 10.3%; p = .287) did not show a difference. CONCLUSION: PJI with co-existing cerclages for fractures were associated with multi-resistant microbes, relapse by the same microbe and early-onset re-infections. Cerclages might be considered a potential source of re-infection during a two-stage exchange. However, statistical weaknesses and a small study group must be considered limitations of the study.

Two-stage revision for periprosthetic joint infection in cemented total hip arthroplasty: an increased risk for failure?

BACKGROUND: The impact of the prior fixation mode on the treatment outcome of chronic periprosthetic joint infection (PJI) of the hip is unclear. Removal of cemented total hip arthroplasty (THA) is particularly challenging and residual cement might be associated with reinfection. This study seeks to compare the results of two-stage revision for PJI in cemented and cementless THA. METHODS: We reviewed 143 consecutive patients undergoing two-stage revision THA for PJI between 2013 and 2018. Thirty-six patients with a fully cemented (n = 6), hybrid femur (n = 26) or hybrid acetabulum (n = 4) THA (cemented group) were matched 1:2 with a cohort of 72 patients who underwent removal of a cementless THA (cementless group). Groups were matched by sex, age, number of prior surgeries and history of infection treatment. Outcomes included microbiological results, interim re-debridement, reinfection, all-cause revision, and modified Harris hip scores (mHHS). Minimum follow-up was 2 years. RESULTS: Compared with PJI in cementless THA, patients undergoing removal of cemented THA had increasingly severe femoral bone loss (p = 0.004). Patients in the cemented group had an increased risk for positive cultures during second-stage reimplantation (22% compared to 8%, p = 0.043), higher rates of reinfection (22% compared to 7%, p = 0.021) and all-cause revision (31% compared to 14%, p = 0.039) compared to patients undergoing two-stage revision of cementless THA. Periprosthetic femoral fractures were more frequent in the group of patients with prior cementation (p = .004). Mean mHHS had been 37.5 in the cemented group and 39.1 in the cementless group, and these scores improved significantly in both groups (p < 0.01). CONCLUSION: This study shows that chronic infection in cemented THA might be associated with increased bone loss, higher rates of reinfection and all-cause revision following two-stage revision. This should be useful to clinicians counselling patients with hip PJI and can guide treatment and estimated outcomes.

Elevated ESR and CRP Prior to Second-Stage Reimplantation Knee Revision Surgery for Periprosthetic Joint Infection Are Associated with Increased Reinfection Rates.

Although two-stage revision surgery is considered as the most effective treatment for managing chronic periprosthetic joint infection (PJI), there is no current consensus on the predictors of optimal timing to second-stage reimplantation. This study aimed to compare clinical outcomes between patients with elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) prior to second-stage reimplantation and those with normalized ESR and CRP prior to second-stage reimplantation. We retrospectively reviewed 198 patients treated with two-stage revision total knee arthroplasty for chronic PJI. Cohorts included patients with: (1) normal level of serum ESR and CRP (n = 96) and (2) elevated level of serum ESR and CRP prior to second-stage reimplantation (n = 102). Outcomes including reinfection rates and readmission rates were compared between both cohorts. At a mean follow-up of 4.4 years (2.8-6.5 years), the elevated ESR and CRP cohort demonstrated significantly higher reinfection rates compared with patients with normalized ESR and CRP prior to second-stage reimplantation (33.3% vs. 14.5%, p < 0.01). Patients with both elevated ESR and CRP demonstrated significantly higher reinfection rates, when compared with patients with elevated ESR and normalized CRP (33.3% vs. 27.6%, p = 0.02) as well as normalized ESR and elevated CRP (33.3% vs. 26.3%, p < 0.01). This study demonstrates that elevated serum ESR and/or CRP levels prior to reimplantation in two-stage knee revision surgery for chronic PJI are associated with increased reinfection rate after surgery. Elevation of both ESR and CRP were associated with a higher risk of reinfection compared with elevation of either ESR or CRP, suggesting the potential benefits of normalizing ESR and CRP prior to reimplantation in treatment of chronic PJI.

Is Ankle Arthrodesis With an Ilizarov External Fixator an Effective Treatment for Septic Ankle Arthritis? A Study With a Minimum of 6 Years of Follow-up.

BACKGROUND: Septic ankle arthritis is a devastating clinical problem with a high potential for permanent disability and amputation. Successful treatment of septic ankle arthritis remains a challenge for the surgeon and patient. Ankle arthrodesis combined with radical debridement may be an effective option to eradicate infection and salvage the limb. Although numerous fusion methods have been proposed, there is controversy about the most effective technique. QUESTIONS/PURPOSES: At a minimum follow-up of 6 years after ankle arthrodesis performed using an Ilizarov external fixator, we asked, (1) In what proportion of patients was bony fusion achieved? (2) What complications were observed, and what reoperations were performed in these patients? (3) How much did patient-reported outcomes improve from before surgery to the most recent follow-up in this group? METHODS: Between April 2010 to March 2015, we treated 59 patients for septic ankle arthritis. Of those, we considered patients who were at least 18 years of age with irreversible destruction of the joint as potentially eligible. During that time period, all patients met the prespecified criteria and were treated with ankle arthrodesis using an Ilizarov external fixator. Two percent (one of 59) of patients were excluded because they died in the second year after surgery for reasons unrelated to the procedure, and another 7% (four of 59) of patients were excluded because they were lost before the minimum study follow-up interval of 6 years. Finally, 92% (54 of 59) of patients were analyzed at a mean follow-up time of 9 ± 1 years. A total of 61% (33 of 54) were men, and they had a mean age of 48 ± 12 years. Forty-six percent (25 of 54) of patients were smokers, and 13% (seven of 54) of patients had Type 2 diabetes mellitus. All patients received radical debridement and primary arthrodesis with an Ilizarov external fixator, followed by antibiotic therapy. Postoperatively, patients were instructed to perform lower extremity functional exercises and external fixator care; weightbearing ambulation as tolerated was encouraged as early as possible. Fusion was assessed with a radiographic review that was performed by an individual who was not involved in the surgical care of these patients. We defined bony fusion as continuous trabeculae and complete cortical bridging in the fusion interface achieved before 9 months; delayed union was defined as fusion achieved by 9 to 12 months; and nonunion was defined as patients in whom fusion was not achieved by 12 months. Complications and reoperations were tallied through a record review that was performed by an individual who was not involved in the surgical care of these patients. We defined complications as any deviation from the expected postoperative course. We used the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, the VAS active pain score, and the SF-12 questionnaire (including the physical component summary [PCS] score and mental component summary [MCS] score) to assess patient-reported outcomes. The minimum clinically important difference (MCID) for the AOFAS score was 30 points of 100, the MCID for the VAS active pain score was 2 points of 10, and the MCID of PCS and MCS scores was 7 points and 9 points, respectively. RESULTS: Primary bony fusion was achieved in 94% (51 of 54) of patients. Delayed union was found in 2% (one of 54) of patients. Nonunion was found in 6% (three of 54); one of these patients underwent autologous bone grafting during revision, and bony fusion was ultimately achieved. Final bony fusion was achieved in 96% (52 of 54) of patients. Recurrent infection was found in 2% (one of 54). The median (range) AOFAS score improved from 28 points (8 to 59) before surgery to 80 points (52 to 86) at the most recent follow-up (median difference 52; p < 0.001). The median (range) VAS active pain score decreased from 8 points (6 to 9) before surgery to 2 points (0 to 5) at the most recent follow-up (median difference -6; p < 0.001). For the Short Form 12-item score, the median (range) PCS score improved from 0 points (0 to 30) before surgery to 70 points (40 to 95) at the most recent follow-up (median difference 70; p < 0.001), and the median (range) MCS score improved from 46 points (21 to 75) before surgery to 75 points (50 to 92) at the most recent follow-up (median difference 29; p < 0.001). CONCLUSION: Ankle arthrodesis with Ilizarov external fixation might eradicate an infection and restore foot function in patients with septic ankle arthritis. However, patients should be fully informed of the complications related to the external fixator, such as pin-tract infections, recurrent infection, and nonunion. Standardized and professional pin care is important. Additionally, because Ilizarov external fixators can be inconvenient to the patients' daily lives, future studies should explore how psychologic support affects patients who undergo ankle arthrodesis with these devices. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Infecciones respiratorias recurrentes en paciente escolar, asociadas a Síndrome de Mounier-Khün: reporte de caso / Recurrent respiratory infections associated with Mounier-Khün Syndrome in a school patient: clinical case report / Infecções respiratórias recorrentes associadas à Síndrome de Mounier-Khün num paciente escolar: relato do caso

El síndrome de Mounier Kühn es una patología infrecuente de la vía aérea, caracterizada por una dilatación anormal de tráquea y bronquios. Se debe sospechar ante la presencia de infecciones broncopulmonares recurrentes e irritación traqueobronquial. El diagnóstico se lleva a cabo a través de la medición del diámetro traqueal en tres segmentos de su anatomía, a través de tomografía torácica. Se presenta el caso de un paciente masculino escolar de 10 años de edad, con antecedentes de infecciones respiratorias recurrentes, hospitalizado por un cuadro neumónico; los hallazgos reportados en la tomografía de tórax corresponden a traqueobroncomegalia además de incremento del diámetro esofágico. El tratamiento de esta entidad es sintomático con medidas de sostén y fisioterapia pulmonar.

Mounier Kühn syndrome is a rare airway pathology characterized by abnormal dilatation of the trachea and bronchi. It should be suspected in the presence of recurrent bronchopulmonary infections and tracheobronchial irritation. The diagnosis is made by measuring the tracheal diameter in three segments of its anatomy, through thoracic tomography. We present the case of a 10 year-old male school boy with a history of recurrent respiratory infections, hospitalized for a pneumonic condition; the findings reported in the thoracic tomography correspond to a tracheobronchomegaly in addition to an increase of the esophageal diameter. The treatment of this entity is symptomatic with supportive measures and pulmonary physical therapy.

A síndrome de Mounier Kühn é uma patologia incomumdas vias aéreas, caracterizada por dilatação anormal da traqueia e brônquios. Devese suspeitar na presença de infecções broncopulmonares recorrentes e irritação traqueobrônquica. O diagnóstico é realizado através da medida do diâmetro traqueal em três segmentos de sua anatomia, através da tomografia de tórax. Apresentamos o caso de um paciente escolar de 10 anos de idade, do sexo masculino, com história de infecções respiratórias de repetição, internado por sintomas pneumônicos; os achados relatados na tomografia de tórax correspondem a uma traqueobroncomegalia, além de aumento do diâmetro esofágico. O tratamento dessa entidade é sintomático com medidas de suporte e fisioterapia pulmonar.

Elucidating reasons of COVID-19 re-infection and its management strategies.

BACKGROUND AND AIMS: Reinfection is gradually being recognised after symptomatic or asymptomatic COVID-19 infection. We try to elucidate various explanations behind COVID-19 reinfection and suggest possible strategies to counteract this threat. METHODS: We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'Pandemics', 'Reinfection', 'Vaccines' and 'India' on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in March 2021 and first half of April 2021 during the current COVID-19 pandemic. Epidemiology, risk factors and trends of reinfection were assessed. RESULTS: A multitude of factors have been associated with rising incidence of COVID-19 reinfection in India and across the world. Emergence of 'Variants of Concern (VOC)', pandemic fatigue and disregard of infection prevention strategies appear to be the most obvious reasons. CONCLUSIONS: COVID-19 reinfection is an emerging concern amongst the worldwide population with newer mutant strains demonstrating increasing transmissibility and responsible for continuing waves of the pandemic. COVID Appropriate Behaviour (CAB), improvised vaccines and enhanced vaccination drives are necessary to mitigate global threat.

Reactivations of Latent Viral Infections Are Associated with an Increased Thr389 p70S6k Phosphorylation in Peripheral Lymphocytes of Renal Transplant Recipients.

Reactivations of BK polyoma virus (BKPyV) and human cytomegalovirus (HCMV) frequently cause life- and graft-threatening complications after renal transplantation. Both viruses are dependent on the mTOR pathway for replication. In this study we investigated the association of viral replication with mTOR activity in peripheral lymphocytes of renal transplant recipients. A flow-cytometry based assay for the measurement of Thr389 p70S6k phosphorylation, a surrogate marker of the mTOR pathway was established. Forty-eight adult renal transplant recipients were recruited to measure p70S6k activity in their peripheral blood mononuclear cells. This data set in conjunction with information concerning previous replication of BKPyV and HCMV was examined for correlations. Episodes of BKPyV replication were significantly associated with increased p70S6k phosphorylation in CD4+ T lymphocytes (p = 0.0002) and CD19+ B lymphocytes (p = 0.0073). HCMV infection of patients with a high-risk HCMV constellation of donor and recipient (D+/R-) was associated with increased p70S6k phosphorylation in CD19+ B lymphocytes (p = 0.0325). These associations were found to be independent of the trough levels of the immunosuppressive drugs. Conclusion: P70S6k phosphorylation in peripheral lymphocytes is associated with BKPyV reactivations and to a lesser extent with HCMV infections in renal transplant recipients.

Pancytopenia, Recurrent Infection, Poor Wound Healing, Heterotopia of the Brain Probably Associated with A Candidate Novel de Novo CDC42 Gene Defect: Expanding the Molecular and Phenotypic Spectrum.

CDC42 (cell division cycle protein 42) belongs to the Rho GTPase family that is known to control the signaling axis that regulates several cellular functions, including cell cycle progression, migration, and proliferation. However, the functional characterization of the CDC42 gene in mammalian physiology remains largely unclear. Here, we report the genetic and functional characterization of a non-consanguineous Saudi family with a single affected individual. Clinical examinations revealed poor wound healing, heterotopia of the brain, pancytopenia, and recurrent infections. Whole exome sequencing revealed a de novo missense variant (c.101C > A, p.Pro34Gln) in the CDC42 gene. The functional assays revealed a substantial reduction in the growth and motility of the patient cells as compared to the normal cells control. Homology three-dimensional (3-D) modeling of CDC42 revealed that the Pro34 is important for the proper protein secondary structure. In conclusion, we report a candidate disease-causing variant, which requires further confirmation for the etiology of CDC42 pathogenesis. This represents the first case from the Saudi population. The current study adds to the spectrum of mutations in the CDC42 gene that might help in genetic counseling and contributes to the CDC42-related genetic and functional characterization. However, further studies into the molecular mechanisms that are involved are needed in order to determine the role of the CDC42 gene associated with aberrant cell migration and immune response.

Exploring the Seasonal Drivers of Varicella Zoster Virus Transmission and Reactivation.

Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multidecadal latency of VZV in the body and subsequent viral reactivation-which occurs in approximately 30% of individuals-are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level data sets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fitted 14 mathematical models examining the biological drivers of chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity-boosting, wherein reexposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested that the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ambient levels of ultraviolet radiation being correlated with shingles reactivation.

Hepatitis C: clinical management and debated issues.

Hepatitis C virus represents an important global health issue with 71 million of infected people in the word. Direct-acting antivirals are quite new molecules that hit specific Hepatitis C virus proteins useful for viral replication and assembly. Notably, Direct-acting antivirals bring to high sustained virological response rates showing also a great safety profile. This treatment revolution had an impact on transplantation world, in fact the number of liver transplants due to Hepatitis C virus-related cirrhosis and hepatocellular carcinoma is quickly decreasing. Even if this therapy has achieved excellent results in terms of morbility and mortality rates' reduction, there are some debated issues to consider. In the present review the main clinical challenges in every-day management of Hepatitis C virus patients treated with Direct-acting antivirals and the debated effects of viral clearance (metabolic, cardiovascular, immunologic and neoplastic) are discussed. The detection of barriers that can preclude the delivery of Hepatitis C virus care, is the most complex challenge for the scientific community. To obtain the Hepatitis C virus global eradication by 2030, as the World Health Organization has set, will be complex and laborious and will need a further multilevel effort.