Mitotic DNA synthesis is caused by transcription-replication conflicts in BRCA2-deficient cells.

Aberrant replication causes cells lacking BRCA2 to enter mitosis with under-replicated DNA, which activates a repair mechanism known as mitotic DNA synthesis (MiDAS). Here, we identify genome-wide the sites where MiDAS reactions occur when BRCA2 is abrogated. High-resolution profiling revealed that these sites are different from MiDAS at aphidicolin-induced common fragile sites in that they map to genomic regions replicating in the early S-phase, which are close to early-firing replication origins, are highly transcribed, and display R-loop-forming potential. Both transcription inhibition in early S-phase and RNaseH1 overexpression reduced MiDAS in BRCA2-deficient cells, indicating that transcription-replication conflicts (TRCs) and R-loops are the source of MiDAS. Importantly, the MiDAS sites identified in BRCA2-deficient cells also represent hotspots for genomic rearrangements in BRCA2-mutated breast tumors. Thus, our work provides a mechanism for how tumor-predisposing BRCA2 inactivation links transcription-induced DNA damage with mitotic DNA repair to fuel the genomic instability characteristic of cancer cells.

The Hammer and the Dance of Cell Cycle Control.

Cell cycle checkpoints secure ordered progression from one cell cycle phase to the next. They are important to signal cell stress and DNA lesions and to stop cell cycle progression when severe problems occur. Recent work suggests, however, that the cell cycle control machinery responds in more subtle and sophisticated ways when cells are faced with naturally occurring challenges, such as replication impediments associated with endogenous replication stress. Instead of following a stop and go approach, cells use fine-tuned deceleration and brake release mechanisms under the control of ataxia telangiectasia and Rad3-related protein kinase (ATR) and checkpoint kinase 1 (CHK1) to more flexibly adapt their cell cycle program to changing conditions. We highlight emerging examples of such intrinsic cell cycle checkpoint regulation and discuss their physiological and clinical relevance.

53BP1-mediated recruitment of RASSF1A to ribosomal DNA breaks promotes local ATM signaling.

DNA lesions occur across the genome and constitute a threat to cell viability; however, damage at specific genomic loci has a relatively greater impact on overall genome stability. The ribosomal RNA gene repeats (rDNA) are emerging fragile sites. Recent progress in understanding how the rDNA damage response is organized has highlighted a key role of adaptor proteins. Here, we show that the scaffold tumor suppressor RASSF1A is recruited to rDNA breaks. RASSF1A recruitment to double-strand breaks is mediated by 53BP1 and depends on RASSF1A phosphorylation at Serine 131 by ATM kinase. Employing targeted rDNA damage, we uncover that RASSF1A recruitment promotes local ATM signaling. RASSF1A silencing, a common epigenetic event during malignant transformation, results in persistent breaks, rDNA copy number alterations and decreased cell viability. Overall, we identify a novel role for RASSF1A at rDNA break sites, provide mechanistic insight into how the DNA damage response is organized in a chromatin context, and provide further evidence for how silencing of the RASSF1A tumor suppressor contributes to genome instability.

When the RAP (80) fades out, you can hear BRCA1 RING.

The tumor suppressor protein BRCA1 plays an important role in DNA repair by homologous recombination. Despite being encoded by the first familial breast and ovarian cancer gene identified, how BRCA1 is recruited to sites of DNA damage to execute its repair functions has remained poorly understood. Several recent studies highlight the role of its constitutive interaction partner BARD1 in this process. In this issue, parallel work by Sherker et al (2021) focused on a second route of BRCA1 recruitment, connected to the BRCA1-A complex protein RAP80. Studying BRCA1 recruitment in RAP80-deficient cells exposed a critical role for the BRCA1 RING domain and its associated ubiquitin ligase activity. Given that tumors expressing RING-less BRCA1 isoforms can become resistant to therapy, targeting the RAP80 recruitment axis in such tumors might restore effective treatment.

Monitoring Irrigation in Small Orchards with Cosmic-Ray Neutron Sensors.

Due to their unique characteristics, cosmic-ray neutron sensors (CRNSs) have potential in monitoring and informing irrigation management, and thus optimising the use of water resources in agriculture. However, practical methods to monitor small, irrigated fields with CRNSs are currently not available and the challenges of targeting areas smaller than the CRNS sensing volume are mostly unaddressed. In this study, CRNSs are used to continuously monitor soil moisture (SM) dynamics in two irrigated apple orchards (Agia, Greece) of ~1.2 ha. The CRNS-derived SM was compared to a reference SM obtained by weighting a dense sensor network. In the 2021 irrigation period, CRNSs could only capture the timing of irrigation events, and an ad hoc calibration resulted in improvements only in the hours before irrigation (RMSE between 0.020 and 0.035). In 2022, a correction based on neutron transport simulations, and on SM measurements from a non-irrigated location, was tested. In the nearby irrigated field, the proposed correction improved the CRNS-derived SM (from 0.052 to 0.031 RMSE) and, most importantly, allowed for monitoring the magnitude of SM dynamics that are due to irrigation. The results are a step forward in using CRNSs as a decision support system in irrigation management.

Outcome Predictors in Civilian and Iatrogenic Arterial Trauma.

BACKGROUND: Our aim was to identify predictors of mortality and limb loss in iatrogenic and civilian arterial trauma. METHODS: Cases were identified by searching prospectively maintained registries. Multivariable logistic regression was used to identify independent outcome predictors. RESULTS: During the study period, 285 patients with arterial trauma were managed with endovascular (n = 20) or open (n = 265) repair. Iatrogenic injuries increased in frequency during the course of the study, from 23.9% during the first decade to 35.9 and 55.7% during the second and third decade, respectively (p < 0.001). Endovascular management increased in frequency during the course of the study, from 0% during the first decade to 5.1 and 11.1% during the second and third decade, respectively (p = 0.005). Mortality was 9.8%, and limb loss (in cases with injury of the aorta or limb arteries, n = 259) was 6.2%. Independent predictors of mortality included increased age (odds ratio, 95% confidence interval [OR, 95% CI] 1.05 (1.02-1.07), p < 0.001), blunt trauma (OR [95% CI] 4.8 (1.9-12.2), p = 0.001) and the number of RBC units transfused intraoperatively (OR [95% CI] 1.25 (1.1-1.4), p = 0.001). Independent predictors of limb loss included the first half of the study period (OR [95% CI] 3.9 (1.1-14.1), p = 0.04), lower extremity arterial trauma (vs upper extremity, aortic, common or external iliac artery trauma, OR [95% CI] 8.3 (1.9-35.7), p = 0.004), bone fracture (OR [95% CI] 16.9 (4.7-62.5), p < 0.001) and the number of RBC units transfused intraoperatively (OR [95% CI] 1.16 (1.02-1.33), p = 0.024). CONCLUSION: Increasingly iatrogenic in cause and managed by endovascular methods, arterial trauma remains a problem associated with significant mortality and limb loss. Identification of unfavourable outcome predictors may help clinicians involved with arterial trauma to escalate the level of care.

Arthroscopic reduction and fixation of greater tuberosity fractures of the humerus.

BACKGROUND: The optimal technique for the displaced greater tuberosity (GT) fractures remains unclear; those in favor of arthroscopic techniques emphasize on the feasibility of arthroscopic reduction and fixation, while others report that anatomic reduction and osteosynthesis of the fracture are optimal through open surgery. Therefore, we performed this study to evaluate the clinical results of arthroscopic fixation for displaced and/or comminuted GT fractures using a bridging arthroscopic technique. MATERIALS AND METHODS: We studied the files of 11 patients (4 men, 7 women; mean age, 55 years; range, 28-74 years), with an isolated, displaced GT fracture treated with arthroscopic reduction and double-row suture anchor fixation technique from December 2016 to October 2018. All patients were operated at a mean time from their injury of 23 days (range, 1-85 days) using an arthroscopic technique. Any concomitant pathology that was arthroscopically identified was identified and repaired after arthroscopic fixation of the GT fracture. The mean follow-up was 12 months (range, 6-18 months). We evaluated pain using a 0-10 point visual analog scale (VAS), shoulder range of motion, fracture healing, Constant-Murley Shoulder Outcome Score, and patients' satisfaction from the operation. RESULTS: Postoperative radiographs showed anatomic reduction without any displacement of the GT fracture in eight patients and residual displacement of < 3 mm in three patients. All patients significantly improved in VAS score from 8.4 points (range, 7-10 points) preoperatively to 0.9 points (range, 0-3 points) postoperatively. Range of motion was 153 degrees forward flexion (range, 130-170 degrees), 149 degrees abduction (range, 120-170 degrees), 42 degrees external rotation (range, 20-70), and internal rotation between T10 and L3 spinal level. The final mean Constant-Murley Shoulder Outcome Score was 85.8 points (range, 76-94 points); correlation analysis showed that the patients with the higher greater tuberosity fracture displacement had the worst postoperative score (Pearson correlation coefficient -0,85; p = 0.0009), and the patients with nonanatomic reduction had close to average score. All patients were very satisfied with the end result of the operation, even the 3 patients with residual fracture displacement. No patient experienced any postoperative complications. CONCLUSIONS: Arthroscopic reduction and fixation of displaced GT fractures is a feasible minimally invasive procedure for optimal fracture healing and patients satisfaction.

Intraneural ganglion cysts of the peroneal nerve.

BACKGROUND: Intraneural ganglion cysts of the peroneal nerve are rare, and there is lack of evidence for the surgical management of this entity. We performed this study to evaluate the imaging, diagnosis, treatment and outcome of seven patients with intraneural ganglion cysts of the peroneal nerve. MATERIALS AND METHODS: We retrospectively studied the files of seven patients with intraneural ganglion cysts of the peroneal nerve, diagnosed and treated from 2016 to 2019. Diagnostic approach included clinical examination of the leg and foot, magnetic resonance imaging, nerve conduction studies, surgical excision of the cyst and histological examination. The mean follow-up was 2 years (range 1-3.5 years). We evaluated the time and methods for surgical treatment, and the clinical outcomes of the patients. RESULTS: All patients presented symptoms of peripheral compression neuropathy; three patients presented with foot drop. The intraneural ganglion cysts were excised in all cases in addition to knee articular nerve branch transection to avoid cysts recurrence. Postoperatively, all patients experienced complete neurological recovery without clinical evidence of intraneural ganglion cysts recurrences. CONCLUSION: The treating physicians should be aware of intraneural ganglion cysts of the peroneal nerve in patients presenting with limb weakness, sensory deficits at the lateral and anterior side of the leg and foot, paresis or paralysis of the foot and ankle. MR imaging is the imaging modality of choice for a clear and accurate preoperative diagnosis to avoid misdiagnosis and wrong treatment. In case of doubt, these patients should be managed in an orthopedic oncology setting with microsurgery facilities available for complete excision of the intraneural ganglion cyst.

EasyFRAP-web: a web-based tool for the analysis of fluorescence recovery after photobleaching data.

Understanding protein dynamics is crucial in order to elucidate protein function and interactions. Advances in modern microscopy facilitate the exploration of the mobility of fluorescently tagged proteins within living cells. Fluorescence recovery after photobleaching (FRAP) is an increasingly popular functional live-cell imaging technique which enables the study of the dynamic properties of proteins at a single-cell level. As an increasing number of labs generate FRAP datasets, there is a need for fast, interactive and user-friendly applications that analyze the resulting data. Here we present easyFRAP-web, a web application that simplifies the qualitative and quantitative analysis of FRAP datasets. EasyFRAP-web permits quick analysis of FRAP datasets through an intuitive web interface with interconnected analysis steps (experimental data assessment, different types of normalization and estimation of curve-derived quantitative parameters). In addition, easyFRAP-web provides dynamic and interactive data visualization and data and figure export for further analysis after every step. We test easyFRAP-web by analyzing FRAP datasets capturing the mobility of the cell cycle regulator Cdt2 in the presence and absence of DNA damage in cultured cells. We show that easyFRAP-web yields results consistent with previous studies and highlights cell-to-cell heterogeneity in the estimated kinetic parameters. EasyFRAP-web is platform-independent and is freely accessible at: https://easyfrap.vmnet.upatras.gr/.

Lateral arm flap: indications and techniques.

The lateral arm flap (LAF) is a popular flap transfer, which can be applied in many procedures. It was first described in 1982, and till then, even more clinical applications are suggested. It can be used as a free fasciocutaneous or fascial flap to cover small- to medium-sized soft tissue defects in head and neck but also in upper and lower extremity reconstruction, or as an osteocutaneous flap when vascularized bone graft is needed. We present the indications and contraindications, the advantages and disadvantages, as well as the step-by-step technique of harvesting a fasciocutaneous and an osteocutaneous flap and its complications. We conclude that the LAF is a reliable and versatile tool for reconstructive surgery, due to its anatomical characteristics and the low complication rate.

The 100 Top-Cited Articles on Medial Patellofemoral Ligament: A Bibliometric Analysis and Review.

Background: The medial patellofemoral ligament (MPFL) has been investigated widely in the past 30 years, resulting in many research achievements in this field. Purpose: To perform a comprehensive bibliometric analysis to evaluate the 100 top-cited articles on the MPFL. Study Design: Cross-sectional study. Methods: We searched the Scopus database in December 2022 using the terms "medial patellofemoral ligament" OR "MPFL." The search was confined to English-language articles, including technical notes, systematic reviews on clinical outcomes and/or complications, clinical studies, studies regarding complications, and basic science articles (either cadaveric or biomechanical); we excluded letters, case reports, personal opinions, guidelines, editorials, and narrative or other types of reviews. Analysis of the 100 top-cited articles was performed according to total number of citations, average citations per year (ACY), study type, country of origin, journal of publication, affiliated institution, and most published authors. Results: The total number of citations was 16,358 (range of citations per article, 72-692). The majority of articles were published as clinical studies (54%), with cadaveric studies being the second most common (21%). Most studies originated in the United States (32%), with Japan (15%) and Germany (13%) following. The American Journal of Sports Medicine published the majority of the 100 top-cited articles (37/100; 6304 citations) as well as the 10 top-cited articles according to ACY (7/10; mean, 285.14 citations). The most prolific authors were Nomura (8 articles); Burks (6 articles); and Inoue, Sillanpää, and Dreyhaupt (5 articles each). Conclusion: By analyzing the characteristics of the 100 top-cited articles, this study demonstrated that the MPFL is a growing and popular area of research, with the focus varying through timeline trends. Questions regarding MPFL anatomy, isometry, and biomechanics might have been answered adequately, but research regarding optimal fixation technique under various circumstances is still ongoing.

The In Vivo Chondrotoxicity of Single Intra-articular Injection of Local Anesthetic in Rat Cartilage.

Introduction A constant infusion of local anesthetics through pain pumps has been shown to cause chondrolysis. However, there is no general consensus regarding the safety of a single intra-articular injection of local anesthetics. In this experimental study, we examined the rat cartilage for possible histological effects after a single intra-articular administration of lidocaine or ropivacaine. Material and methods Thirty-two male Sprague-Dawley rats, weighing 250-300 grams, were divided into two groups of 16 each. We injected 0.1 ml of either lidocaine 2% (20 mg/ml) or ropivacaine 0.75% (7.5 mg/ml) into the left knee of the rats. The right knee in both groups was used as a control, and an equal amount of normal saline was injected. Each group was further divided into subgroups of four, which were euthanized after one, seven, 21, and 60 days after the initial injection. Knees were excised and prepared for histopathological analysis. A modified version of the Mankin score was used for cartilage damage evaluation. Results No difference regarding cartilage damage was detected after the examination under light microscopy between lidocaine, ropivacaine, and placebo in all specimens. Time elapsed since the initial injection did not affect the results at any time point. Conclusion A single intra-articular injection of local anesthetic did not induce any histological changes in the rat cartilage. Further research is needed to demonstrate the safety of humans.

Capitate Proximal Fragment Migration Compressing the Median Nerve in Scaphocapitate Fracture: A Case Report.

BACKGROUND Scaphocapitate syndrome is a rare clinical entity consisting of a combined scaphoid and capitate fracture along with a 90- or 180-degrees rotation of the proximal capitate fragment. The syndrome is scarcely described in the literature, with proximal migration of the capitate fragment being reported only by Mudgal et al in 1995. Concurrent compression of the median nerve is a highly unfortunate event, suggesting a unique case presented here. CASE REPORT We present a unique case of scaphocapitate fracture-dislocation in a 25-year-old man with volar dislocation of the capitate's fragment deep to the median nerve. X-rays and CT scan were performed and the patient was treated few hours after the injury by a hand specialist, in order to prevent median neuropathy and avascular necrosis of the fragment. Open reduction and internal fixation utilizing a Herbert screw for the scaphoid fracture and 3 additional K-wires was performed. Immediately post-operatively, the acute neurological symptoms had subsided and good reduction was acquired radiologically. One year post-operatively the patient had regained good hand and wrist functionality, with no extension or flexion ROM deficits. CONCLUSIONS Immediate intervention in a specialized center with reduction and fixation utilizing a Herbert screw and K-wires showed favorable 1-year results in our case of scaphocapitate syndrome. The impending complications of median neuropathy and capitate avascular necrosis were avoided despite the high-risk injury pattern.

From lab to mass production: a policy for enabling the licensing of mRNA vaccines.

Using the South African vaccine technology transfer hub supported by the WHO as an example, we show that the know-how needed to move mRNA vaccines from prototype to mass-production acts as an invisible barrier to market entry of mRNA vaccines. Overcoming this barrier relies on scarce human capital. In view of this scarcity and in preparation for the next pandemic, we propose broadening the scope of an existing WHO program, the WHO Academy, so that it coordinates knowledge diffusion initiatives by forming a systematized repository of know-how and a register of experts. As we explain, this proposal has an advantage in overcoming barriers to entry over current approaches of know-how acquisition.

Fracture of femoral neck in modular total hip arthroplasty: a systematic review of the literature.

BACKGROUND: Modular femoral stems have the advantage of anatomic hip reconstruction by restoring the femoral offset thus minimising the bearing surface wear, implant loosening and dislocation. AIM: This study aims to investigate the existing literature on modular neck fractures, to identify predisposing factors and guide the decision-making process in the management of these difficult cases. METHODS: A systematic literature review was conducted until July 2022. PRISMA guidelines were followed, eligibility criteria were set, and methodology assessment of included studies was conducted based on MINORS criteria, size and primary outcome. Data were extracted and analysed thoroughly. RESULTS: 5657 studies were initially screened; the full texts of 124 records were assessed and finally, 32 reports were included. There were 7 clinical studies and 25 case reports. A total of 4825 patients (5204 hips) with a mean age 62.38 years and a mean BMI 29.06 kg/m2 were analysed in the 7 clinical studies. The reported overall weighted revision rate was 0.86%, while the weighted mean modular neck fracture rate was 0.26%. The usual history was sudden experience of hip pain and instability. The average time interval to neck fracture was 4.57 (range 3-4.7) years and a long modular neck was identified in 91.17% of them. Data from case reports showed a mean age and average BMI of 55.85 and 31.63 kg/m2. 82.35% of the patients were male. Necks were fractured after an average time interval of 64.5 ± 8.8 months. CONCLUSIONS: The incidence of modular neck fracture is significant. The profile of a male, obese patient with a long modular neck increased risk of neck fracture. Microstructural investigation of the retrieved implants demonstrated a higher incidence of fracture line in the base of the neck junction and at its anterolateral distal part. Surgeons should be aware of this complication while using or revising such protheses.

Study protocol: biomechanical testing, finite element analysis and prospective, randomized, clinical study of single screw cephalomedullary nailing versus integrated dual interlocking screw fixation for unstable (31A21-3) intertrochanteric fractures in patients > 70 years old.

BACKGROUND: Hip fractures are an increasingly common consequence of falls in older people that are associated with a high risk of death and reduced function. The vast majority of intertrochanteric fractures require surgical treatment to withstand early mobilization and weight bearing, which prevents complications due to prolonged bed rest and aids in fracture healing. METHODS: This study is compromised by two parts, the experimental study and the clinical part. In the first part, a standard 130° nail will be used with the appropriate lag screw(s) and dynamic distal locking in synthetic osteoporotic femurs and the transmission of forces in the proximal femur, measured by a cortical surface-strain distribution, will be evaluated using digital image correlation. Finite element parametric models of the bone, the nails and their interface will be also developed. Finite element computations of surface strains in implanted femurs, after being validated against biomechanical testing measurements, will be used to assist the comparison of the nails by deriving important data on the developed stress and strain fields, which cannot be measured through biomechanical testing. In the other part, will set up a prospective, randomized, comparative clinical study among the Gamma3 and IT cephalomedullary nailing, in order to investigate if there are any statistical important differences in the main radiological measurements and functional status in closed unstable intertrochanteric fractures (A21-3) in patients aged over 70 years old at the 24-week follow-up evaluation using patient reported disease-specific outcomes. DISCUSSION: This study will be the first to compare clinical, radiological and biomechanical measurements of the two different cephalomedullary nails. Our main hypothesis is that the IT nail would provide better radiological outcome and probably better clinical results than the Gama3 nail. Clinical trial registration International Standard Randomized Controlled Trial Number (ISRCTN): https://doi.org/10.1186/ISRCTN15588442 , registered on 19/4/2022.

Terrible Triad of the Shoulder: A Case Series and Literature Review.

INTRODUCTION: The shoulder terrible triad is an underdiagnosed injury pattern consisting of anterior shoulder dislocation, rotator cuff tear, and nerve injury from the brachial plexus in its original description. The purpose of this study is to raise awareness of the condition, suggest treatment strategies, and emphasize the difficulties in treating this condition. METHODS: This case series of seven patients from the same institution. All patients underwent x-rays before and after the reduction of the dislocation, MRI to assess the musculoskeletal injuries, and EMG and clinical examination to assess the nerve lesions. Early arthroscopic repair was opted for the rotator cuff tears. A conservative approach was chosen for the nerve lesions. Active forward flexion and external rotation, Constant score, and Visual to Analogue Scale (VAS) were recorded pre- and post-operatively. RESULTS: All the patients showed an improvement in function postoperatively. However, four of the seven patients did not recover fully. The mean Constant and VAS scores were improved from 15.2 +/- 2.8 (12 to 19) to 67 +/- 16.6 (44 to 86) and from 7.5 +/- 1 (6 to 9) to 2.3 +/- 0.8 (1 to 3), respectively. The patients were followed up for a mean time of 28.2 +/- 10.1 months (18 to 43 months). Time-to-surgery shorter than four weeks showed better results, but not statistically significant. CONCLUSIONS: The diagnosis of the shoulder terrible triad requires a high level of suspicion. Early arthroscopic repair for the rotator cuff tears and waiting for the nerve recovery is suggested. Delayed time from injury to surgery might be related to worse outcomes, but higher-level research is needed in this direction.

Surgical Treatment of Monteggia-Like Lesions With a Modified Boyd Approach.

Introduction: Monteggia-like lesions are rare injuries in adults that include a wide spectrum of complex fracture-dislocations of the proximal ulna and radius. In this retrospective study, we performed a modified Boyd approach and a standard surgical protocol for the treatment of these lesions. Our aim was to evaluate the results of the operative treatment for patients with Monteggia-like lesions, using a modified Boyd approach. Materials and Methods: We present a retrospective study of 14 patients who underwent surgical treatment for Monteggia-like lesions. Preoperative clinical and radiological evaluation was performed. In 5 cases radial head prosthesis was placed, and in 3 cases the radial fracture was stabilized with the use of interfragmental screws. Regarding the proximal ulnar fracture, ORIF-anatomical plate and ORIF-straight plate was used in 12 and 2 cases, respectively. Results: Average clinical follow up was 16.9 months. Postoperatively, the mean Mayo Elbow Performance score was 83.4 points (range 70-100) and the mean visual analog scale was 1.7 (range 0-14). Mean flexion and loss of extension were 122.1° (range 80°-140°) and 21.4° (range 5°-40°), respectively. Mean supination of the forearm was 66.8° (range 50°-80°) and the mean pronation was 67.5° (range 60°-75°). Heterotopic ossification was observed in 3 patients (21.4%) and 1 patient developed stiffness (7.1%). The patient who developed stiffness underwent reoperation for plate removal and arthrolysis, with satisfactory results. Conclusions: The surgical treatment of Monteggia-like lesions in adults remains a challenge. In the present study, the use of a standard surgical protocol, with a modified Boyd approach, successfully restores the movement and stability of the elbow, with a low complication rate.

Septic Tibial Nonunions on Proximal and Distal Metaphysis-A Systematic Narrative Review.

BACKGROUND: Infected nonunion of the tibia represents a challenging complication for orthopedic surgeons and poses a major financial burden to healthcare systems. The situation is even more compounded when the nonunion involves the metaphyseal region of long bones, a rare yet demanding complication due to the poor healing potential of infected cancellous bone; this is in addition to the increased likelihood of contamination of adjacent joints. The purpose of this study was to determine the extent and level of evidence in relation to (1) available treatment options for the management of septic tibial metaphyseal nonunions; (2) success rates and bone healing following treatment application; and (3) functional results after intervention. METHODS: We searched the MEDLINE, Embase, and CENTRAL databases for prospective and retrospective studies through to 25 January 2021. Human-only studies exploring the efficacy of various treatment options and their results in the setting of septic, quiescent, and metaphyseal (distal or proximal) tibia nonunions in the adult population were included. For infection diagnosis, we accepted definitions provided by the authors of source studies. Of note, clinical heterogeneity rendered data pooling inappropriate. RESULTS: In terms of the species implicated in septic tibial nonunions, staphylococcus aureus was found to be the most commonly isolated microorganism. Many authors implemented the Ilizarov external fixation device with a mean duration of treatment greater than one year. Exceptional or good bone and functional results were recorded in over 80% of patients, although the literature is scarce and possible losses of the follow-up were not recorded. CONCLUSION: A demanding orthopedic condition that is scarcely studied is infected metaphyseal tibial nonunion. External fixation seems promising, but further research is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO No. CRD42020205781.