High patient satisfaction with Customized Total Knee Arthroplasty at five year follow-up.

PURPOSE: Despite numerous studies demonstrating promising short-term outcomes of Total Knee Arthroplasty (TKA) with Customized Individually Made (CIM) implants, there is a significant lack of data on their mid-term effectiveness. Given the increasing number of TKAs performed annually, the rising demand for CIM implants, and the associated burden of revision surgeries, understanding the mid-term performance of CIM implants is crucial. Therefore, this study aims to report on the mid-term (minimum 5 years) outcomes of TKA using a CIM implant. METHODS: This retrospective cohort study included a consecutive series of 116 patients who received the ConforMIS® iTotal CR implant between 2015 and 2018. Inclusion criteria were end-stage knee osteoarthritis with coronal deformities below 10° and absence of ligamentous instability. Exclusion criteria included simultaneous bilateral TKA. Patients were followed up at a minimum of five years post-surgery. They completed a questionnaire reporting on satisfaction, pain levels using the Visual Analogue Scale (VAS), current weight, the Oxford Knee Score (OKS), and the Forgotten Joint Score for the knee (FJS-knee). Statistical analysis included descriptive statistics for demographic and clinical variables, and outcomes were reported as means with ranges. RESULTS: The mean follow-up duration was 5.9 ± 0.8 years (range 5-7.4 years). 90% of patients stated they would undergo the same operation again, and 93% were either satisfied or very satisfied. The mean VAS for pain at rest was 2 ± 1.5 (range 0-6) and during exercise was 3 ± 2 (range 0-8). 58 patients (53%) managed to lose weight. The mean OKS was 41 ± 9 points (range 15-48), and the mean FJS-knee was 67 ± 23 points (range 4-100). No severe complications occurred. CONCLUSION: CIM TKA using the ConforMIS® iTotal CR implant can achieve excellent results with 93% of patients being satisfied or very satisfied at mid-term follow-up of five years. Prospective, randomized, and patient-blinded trials comparing off-the-shelf (OTS) TKAs with CIM implants are necessary to evaluate whether these implants are superior or not.

Female sex as a negative predictor of outcomes of ankle arthrodesis: a retrospective comparative monocentric study.

BACKGROUND: End-stage post-traumatic osteoarthritis of the ankle joint may require arthrodesis if conservative treatment fails and a decision against total ankle replacement is made. We aimed to compare the sex-specific differences in outcomes and objectify them using validated specific scores. METHODS: Between 2010 and 2021, 221 patients underwent ankle arthrodesis at our institution, including 143 men (MAA) and 78 women (FAA). In addition to demographic data, the aetiology of osteoarthritis, the Foot Function Index (FFI-D), the Olerud-Molander Score (OMAS), and the Short Form-12 questionnaire (SF-12) were collected in this monocentric study. The mean follow-up time was 5.8 years. End-stage osteoarthritis was mostly due to ankle fractures as a result of sprains, falls, and road traffic accidents. RESULTS: Post-operatively, the mean FFI-D for pain was 17.3 (MAA: 14.7; FAA 22.2) and 43.9 for function (MAA: 41.1; FAA 49.5); the mean OMAS was 58.2; and the mean SF-12 physical component score was 42.5. Women achieved significantly worse results in all scores; only the mental component summary of the SF-12 did not differ between the sexes (p > 0.05). Approximately 34% of women stated that the result in terms of gait pattern was worse than expected (MAA 16.1%; p < 0.05). Again, significantly more men stated that the result was better than expected (MAA: 48.3%; FAA: 31.5%, p < 0.05). CONCLUSIONS: The fact that the clinical results were significantly worse in women after ankle arthrodesis should be considered when determining the indication. However, the expectations of men and women also need to be individually adjusted.

Validation of the hip disability osteoarthritis outcome Score-12 shortform in a German cohort.

INTRODUCTION: To consider the inherent respondent burden of PROMs, the HOOS-12 as a shortform of the well-established HOOS questionnaire has been published. While the HOOS-12 has been validated in an initial study, further evaluation in other, non-English speaking cohorts is necessary. We therefore aimed to evaluate responsiveness, convergent construct validity, internal consistency, and floor and ceiling effects of the HOOS-12 in a cross-sectoral german cohort. MATERIALS AND METHODS: European Quality of Life 5 Dimensions scores and HOOS data of patients undergoing total hip arthroplasty (THA) were used for the analyses. HOOS-12 scores were calculated from the full length HOOS. Statistical analysis was conducted, investigating internal consistency, floor and ceiling effects, convergent and discriminant validity, responsiveness, and known-group comparisons. RESULTS: A ceiling effect was present for postoperative HOOS-12 score and its pain, function and QoL subscales. Internal consistency was high between baseline and all follow ups, inter-item correlation was high (Cronbach's alpha > 0.30) for HOOS-12 score and all subscales. Correlation of HOOS-12 pain with HOOS pain was high (r = 0.9). Correlation of HOOS-12 function with HOOS ADL and HOOS S/R was high (r = 0.89, r = 0.74). Correlation was moderate between HOOS-12 pain and HOOS-12 function with its respective EQ-5D score (r=-0.58, r=-0.59). CONCLUSION: The HOOS-12 showed good convergent construct validity and is responsive to changes in pain, function, QoL and hip impact between preoperatively and 1 year postoperatively. A substantial ceiling effect for all subscales at 1 year postoperatively limits the ability to capture variance across particularly well performing patients. TRIAL REGISTRATION: The Trial is registered with the German Clinical Trials Register ( https://www.drks.de ; DRKS00013972; 23 March 23, 2018).

Reliability of Angle Measurements Based on the Epiphyseal Scar for Knee Osteotomy: An International Multicenter Radiographic Study.

Background: The proximal tibial epiphyseal inclination can be used as a prognostic factor for good results after knee osteotomy and measured using the tibial bone varus angle (TBVA). This angle depends on the visibility of the epiphyseal plate, which has shown poor reproducibility when measured on standard radiographs by conventional methods. Purpose: To evaluate the measurement reliability of the TBVA and other angles based on the epiphyseal scar using a digital image display. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 100 whole-leg radiographs were analyzed twice by 3 orthopaedic surgeons from 2 countries in a blinded and randomized manner. Observers measured the hip-knee-ankle angle, mechanical lateral distal femoral angle, medial proximal tibial angle, and TBVA. The growth plate-tibial plateau (GPTP) angle, defined as the angle between the epiphyseal scar and tibial plateau, was measured; this angle has not yet been described for osteotomy. In addition, a modified version of the TBVA (mTBVA), defined as that between the epiphyseal scar, its center, and the center of the talus, was measured. The Ahlbäck score for osteoarthritis and a 3-grade score for epiphyseal scar visibility were also determined. The reliability of the angle measurements and scoring was evaluated using the Fleiss kappa and intraclass correlation coefficient (ICC). Results: The scores for epiphyseal scar visibility showed fair interobserver (Fleiss kappa correlation coefficient [κ] = 0.29-0.35) and strong intraobserver (Fleiss κ = 0.62-0.69) reliability. TBVA, GPTP angle, and mTBVA measurements showed good interobserver reliability (ICC, 0.76-0.77), while the GPTP angle achieved excellent intraobserver reliability (ICC, >0.9). Conclusion: Using digital image display, angles that depend on the epiphyseal scar-such as TBVA, GPTP angle, and mTBVA-can achieve acceptable measurement reliability despite the low agreement on the visibility of the epiphyseal scar.

Bucket-Handle Meniscal Tears Might Not Be an Urgency: The Time to Meniscus Repair Does Not Seem to Affect the Mid-Term Outcome-A Retrospective Study of Sixty Tears with a Mean Follow-Up of 6 Years.

Background: Bucket-handle meniscal tears are mostly treated arthroscopically. However, there is no clear evidence as to whether the time to surgery impacts the outcome and whether or not lesions should be treated urgently. Methods: Sixty patients were interviewed about the current status of their knee with a mean follow-up of 6.1 years (SD = 3.5). Forty-one patients underwent meniscus repair, and fifteen patients received partial resections. The primary outcome was the rate of reoperation after meniscus repair. Secondary outcomes were pain at rest and during exercise, return to sports, and Tegner and Lysholm scores. Results: The average time to surgery was 14.4 days, with no significant impact of surgical timing on the rate of reoperation. Furthermore, no significant differences were found in pain levels, return to sports, or Tegner and Lysholm scores based on the timing of surgery. Conclusions: In our cohort, the time to surgery was not a prognostic factor for the reoperation rate or postoperative outcome in repairing bucket-handle meniscal tears. Therefore, arthroscopic repair should not be performed in an emergency setting but conducted after careful planning by experienced arthroscopy surgeons. Regarding the return to sports, postoperative factors such as rehabilitation protocols or surgical techniques could be more important than the time to surgery.

Proximal humeral fractures in children - controversies in decision making.

BACKGROUND: Proximal humeral fractures in children are rare and usually treated non-operatively, especially in children younger than ten. The decision between operative and non-operative treatment is mostly based on age and fracture angulation. In the current literature, diverging recommendations regarding fracture angulation that is still tolerable for non-operative treatment can be found. Besides, there is no consensus on how fracture angulation should be determined. This study aimed to determine whether leading experts in pediatric trauma surgery in Germany showed agreement concerning the measurement of fracture angulation, deciding between operative and non-operative treatment, and choosing a treatment modality. METHODS: Twenty radiographs showing a proximal humeral fracture and the patient's age were assessed twice by twenty-two senior members of the "Section of Pediatric Traumatology of the German Association for Trauma Surgery". Experts determined the fracture angulation and chose between several operative and non-operative treatment modalities. The mean of individual standard deviations was calculated to estimate the accuracy of single measurements for fracture angulation. Besides Intra-Class Correlation and Fleiss' Kappa coefficients were determined. RESULTS: For fracture angulation, experts showed moderate (ICC = 0.60) interobserver and excellent (ICC = 0.90) intraobserver agreement. For the treatment decision, there was fair (Kappa = 0.38) interobserver and substantial (Kappa = 0.77) intraobserver agreement. Finally, experts preferred ESIN over K-wires for operative and a Gilchrist over a Cuff/Collar for non-operative treatment. CONCLUSIONS: Firstly, there is a need for consensus among experts on how fracture angulation in PHFs in children should be reliably determined. Our data indicate that choosing one method everybody agrees to use could be more helpful than using the most sophisticated. However, the overall importance of fracture angulation should also be critically discussed. Finally, experts should agree on treatment algorithms that could translate into guidelines to standardize the care and perform reliable outcome studies. LEVEL OF EVIDENCE: III.

A Lightweight Browser-Based Tool for Collaborative and Blinded Image Analysis.

Collaborative manual image analysis by multiple experts in different locations is an essential workflow in biomedical science. However, sharing the images and writing down results by hand or merging results from separate spreadsheets can be error-prone. Moreover, blinding and anonymization are essential to address subjectivity and bias. Here, we propose a new workflow for collaborative image analysis using a lightweight online tool named Tyche. The new workflow allows experts to access images via temporarily valid URLs and analyze them blind in a random order inside a web browser with the means to store the results in the same window. The results are then immediately computed and visible to the project master. The new workflow could be used for multi-center studies, inter- and intraobserver studies, and score validations.

Functional outcomes after intramedullary nailing (C-Nail®) of severe calcaneal fractures with mean follow-up of 36 months.

PURPOSE: Calcaneal fractures (CFs) are rare but potentially debilitating injuries. Apart from the open, far lateral or sinus tarsi approach, operative treatment can be performed minimally invasive and percutaneously with intramedullary nailing. In this study, we sought to investigate the functional outcome of severe CFs treated with the C-Nail® implant. METHODS: Twenty-two CFs (9 × Sanders III and 8 × Sanders IV), operated between 2016 and 2019, were followed up with a mean duration of 36 (± 11) months. The AOFAS score, pre- and postoperative Böhler angles, wound healing disorders, and patient-reported outcome measures (PROMs) like pain levels and return to work/sport levels were assessed. RESULTS: The mean AOFAS score was 72.0 (± 9.8). Four patients sustained wound healing disorders, yet no implant-associated surgical revision was required. Fifty percent of patients were pain-free within 1 year. Within 1 year, about 50% of the patients could return to sports, and about 80% of the patients could return to work. PROMs and functional results align with those from other implants reported in the literature. CONCLUSION: Intramedullary nailing of severe CFs with the C-Nail® implant can be considered a safe treatment alternative that yields acceptable results at mid-terms.

Radiographic Evidence of Sufficient Transverse Plane Alignment after Weil Osteotomy without Screw Fixation.

Weil osteotomy is a proven procedure to restore the harmonic distal parabola of the forefoot. In addition to the proximal displacement of the head in the sagittal plane, a displacement in the transverse plane may be necessary, with the refixation of the displaced metatarsal head historically performed by screw fixation. We aimed to determine the radiological differences among 136 feet of 127 patients with 256 Weil osteotomies retrospectively enrolled and divided into groups with (n = 182) and without (n = 74) screw fixation. Demographic data, radiographic union, pre- and postoperative metatarsal angles, and differences in the dorsoplantar view were evaluated. The mean follow-up period was 3.6 months. The mean preoperative metatarsophalangeal angle was 9.24°, and the mean postoperative angle was 12.99°. The restoration of the transversal alignment plane was equally successful in both groups, with a mean extent of angle correction of 10.58°. No nonunions of the osteotomized metatarsals were observed. The radiographic comparisons revealed no significant difference between the groups (p > 0.05). However, visibility of the joint space of the metatarsophalangeal joint was achieved significantly more often in the group without screw fixation (p < 0.05). In the absence of bony malunion and the satisfactory restoration of a harmonious parabola of the forefoot, apparently there does not appear to be a necessity for regular screw fixation after Weil osteotomy based on the available data from the present study.

[Disproportionately increased incidence of proximal femoral fractures in a level one trauma center : Epidemiological analysis from 2016 to 2022]. / Überproportional angestiegene Inzidenz proximaler Femurfrakturen in einem Level-One-Traumazentrum : Epidemiologische Analyse von 2016 bis 2022.

BACKGROUND: Proximal femoral fractures represent the most frequent fracture entity in Germany accounting for more than 20% of all fractures. According to a decision of the Federal Joint Committee from 2019, proximal femoral fractures also have to be surgically treated within 24 h. In order to quantify a subjectively perceived increase in workload in trauma surgery at a supraregional trauma center, a retrospective analysis of the number of surgically treated proximal femoral fractures was performed. Proximal femoral fractures were chosen due to their high incidence and homogeneous treatment. METHODS: Using ICD-10 codes, all surgically treated proximal femoral fractures from 2016 to 2022, including the patient's zip code, were retrieved from the database of the trauma center. RESULTS: The number of surgically treated proximal femoral fractures doubled from 2016 to 2022. The highest increase (60%) was recorded from 2020 to 2022. Heat maps show an increase in the catchment area radius as well. CONCLUSION: When compared (inter)nationally, a disproportionate increase in the amount of surgically treated proximal femoral fractures was recorded at the trauma center studied. The increase of the catchment area radius and the number of patients treated in the urban area show that less and less hospitals participate in emergency treatment. Possible explanations are a lack of resources aggravated by the recent COVID-19 pandemic and a lack of qualified personnel, interface problems between the federal states or the strict requirements of the Federal Joint Committee in the treatment of proximal femoral fractures. It must be assumed that there is a clearly increased workload for all professions involved in the trauma center investigated, although the infrastructure has remained unchanged.

Can we separately measure glenoid vs. humeral lateralization and distalization in reverse shoulder arthroplasty?

BACKGROUND: Lateralization and distalization in reverse shoulder arthroplasty (RSA) can be measured on anteroposterior (AP) radiographs using 2 previously described angles: lateralization shoulder angle (LSA) and distalization shoulder angle (DSA). However, these 2 angles measure global lateralization and distalization but do not allow to differentiate how much lateralization or distalization are attributable to the glenoid and the humerus. We hypothesized that new angles could allow us to separately measure glenoid vs. humeral lateralization and distalization. A more precise understanding of independent glenoid and humeral contributions to lateralization and distalization may be beneficial in subsequent clinical research. METHOD: Retrospective analysis of postoperative AP radiographs of 100 patients who underwent primary RSA for cuff-tear arthropathy, massive cuff tear, or glenohumeral osteoarthritis were analyzed. The new angles that we proposed use well-known bony landmarks (the acromion, glenoid, and humerus) and the most lateral point of the glenosphere, which we termed the "glenoid pivot point" (GPP). For lateralization, we used the GPP to split LSA into 2 new angles: glenoid lateralization angle (GLA) and humeral lateralization angle (HLA). For distalization, we introduced the modified distalization shoulder angle (mDSA) that can also be split into 2 new angles: glenoid distalization angle (GDA) and humeral distalization angle (HDA). Three orthopedic surgeons measured the new angles, using the online tool Tyche. Mean values with overall and individual standard deviations as well as intraclass correlation coefficients (ICCs) were calculated. RESULTS: Because the angles form a triangle, the following equations can be made: LSA = GLA + HLA, and mDSA = GDA + HDA. All angles showed excellent inter- and intraobserver reliability (ICC = 0.92-0.97) with low means of individual standard deviations that indicate a precision of 2° for each angle. CONCLUSION: Use of the most lateral part of the glenosphere (termed glenoid pivot point) allows us to separately measure glenoid vs. humeral lateralization and distalization. The 4 new angles (HLA, GLA, GDA, HDA) described in the present study can be used on true AP radiographs, routinely obtained after shoulder replacement, and the measured angles may be used with all types of reverse prostheses available.

A Novel Tool for Collaborative and Blinded Orthopedic Image Analysis.

Image analysis plays a central role in orthopedics and research but comes with many challenges, including anonymization, bias, and achieving efficient analyses using multiple independent observers. Appropriate software is still lacking. Tyche is a free online tool that displays images in a random order without showing any metadata. Additionally, when using Tyche, observers can store results in the same window, and the final results are immediately visible to the project manager. In this study, we compared results from Tyche with those from a validated tool. One hundred pelvic radiographs were analyzed separately by five orthopedic surgeons using both Tyche and the validated software. Common orthopedic measurement modalities and scores were determined. The methods were compared using intra-class correlations and Fleiss' kappa coefficients as well as Bland-Altman plots. Significant correlations ranging from r = 0.17 (Kallgren and Lawrence Score) to r = 0.99 (area measurements) were calculated for inter- and intraobserver agreements between the two tools for all measurements. The Bland-Altman plots indicated the non-inferiority of either tool. The images were analyzed significantly faster when Tyche was used. We conclude that Tyche is a valid tool for use in orthopedic image analysis. Tyche could be utilized for determining inter- and intraobserver agreements, in multicenter studies and for score validations.

Restoration of preoperative tibial alignment improves functional results after medial unicompartmental knee arthroplasty.

PURPOSE: The alignment obtained after unicompartmental knee arthroplasty (UKA) influences the risk of failure. Kinematic alignment after UKA based on Cartier angle restauration is likely to improve clinical outcomes compared with mechanical alignment. The purpose of this study is to analyze the influence of implant alignment and native knee restoration after UKA using the conventional techniques on clinical outcomes. METHODS: This retrospective study included 144 medial UKA patients from 2015 to 2020. Radiographic measurements were performed pre- and postoperatively. Outliers were defined as follows: Δ Cartier > 3° (difference between the preoperative and postoperative Cartier angle); Δ MPTA (Medial Proximal Tibial angle) and postoperative TCA (Tibial Coronal component Angle) > 3° (difference between the positioning of the tibial implant and the preoperative proximal tibial deformity). The Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Society (IKS) Function and Knee score, the Forgotten Joint Score (FJS), and the Subjective Knee Value (SKV) were evaluated. A Student t test or a non-parametric Wilcoxon test was used for non-normal data to compare pre- and postoperative values for functional scores and angular measurements. The correlation of postoperative angles with functional outcomes was assessed by the Spearman's rank correlation coefficient. RESULTS: During the inclusion period, 214 patients underwent medial UKA, 71 patients were excluded, and 19 were lost to follow-up leaving 124 patients with 144 knees (20 bilateral UKA) included for analysis with a mean follow-up of 54.7 months ± 22.1 (24-95). The Δ Cartier was significantly correlated with IKS function (R2 = 0.06, p < 0.001) and FJS (R2 = 0.05, p < 0.01) scores. The Δ preoperative MPTA-TCA was significantly correlated (p < 0.001) with KOOS (R2 = 0.38), IKS Knee (R2 = 0.17), IKS function (R2 = 0.34), SKV (R2 = 0.08), and FJS (R2 = 0.37) scores. In subgroup analysis, non-outliers (< 3°) for Δ preoperative MPTA-TCA had better KOOS score (Δ = 23.5, p < 0.001) and IKS Function (Δ = 17.7, p < 0.001) compared to outliers (> 3°) patients. CONCLUSION: Functional results after medial UKA can be influenced by implant alignment in the coronal plane with slight clinical improvement when positioning the tibial implant close to the preoperative tibial deformity, rather than by restoring the Cartier angle. This series suggests the interest of a more personalized alignment strategy, but these results will have to be confirmed by other controlled studies. LEVEL OF EVIDENCE: IV, retrospective case series.

Normo-or slightly overcorrection show better results after medial closing wedge high tibial osteotomy.

PURPOSE: The objectives of this study were to evaluate functional results, revision-free survival, and the influence of postoperative alignment on outcomes after MCWHTO. METHODS: This retrospective study included 27 MCWHTO operated on from 2009 to 2021. Radiographic measurements were performed pre- and postoperatively. The HKA (Hip-Knee-Ankle angle), MPTA (Medial Proximal Tibial angle), LDFA (Lateral Distal Femoral Angle), JLO (Joint Line Obliquity), and JLCA (Joint Line Convergence Angle) were evaluated. The Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Society (IKS) Function and Knee Score, and the Subjective Knee Value (SKV) as well as revision-free survival were evaluated. Postoperative alignment and its influence on clinical outcomes were also analysed. RESULTS: The mean follow-up was 61.9 months ± 31.4 (13-124). The HKA, MPTA, and JLCA angles were decreased post-operatively (respectively, Δ = 5.9° ± 2.6, p < 0.001; Δ = 6.1° ± 3.2, p < 0.001 and Δ = 2.5° ± 1.9, p < 0.001). LDFA and JLO were unchanged, post-operatively (respectively, Δ = 0.1° ± 2.2, p = 0.93 and Δ = 1.2° ± 3.3, p = 0.23). Postoperative HKA correlated with knee IKS (R = - 0.15, p = 0.04) and function IKS (R = - 0.44, p = 0.03). Postoperative LDFA correlated with knee IKS(R = 0.8, p < 0.01). Patients with postoperative HKA ≤ 180° had better KOOS (Δ = 12.3, p = 0.04) and IKS function (Δ = 28.1, p < 0.01) than those with HKA > 180°. CONCLUSION: Functional results and revision-free survival after MCWHTO are satisfactory when the deformity is located in the proximal tibia. The joint line obliquity is not significantly altered with small tibial correction and, obtaining an overall neutral or slightly varus alignment under the conditions of this study allowed an improvement in the postoperative clinical scores. The literature is still inconclusive on the ideal alignment for valgus deformities and larger series are needed to draw definitive conclusions. LEVEL OF EVIDENCE: IV, case series.

The Controversial Definition of Normal Toe Alignment.

"Normal" and "abnormal" are frequently used in surgical planning and to evaluate surgical results of the forefoot. However, there is no objectifiable value of metatarsophalangeal angles (MTPAs) 2-5 in the dorsoplantar (DP) view with which to objectively evaluate lesser toe alignment. We aimed to determine which angles are considered to be "normal" by orthopedic surgeons and radiologists. Thirty anonymized radiographs of feet were submitted twice in randomized order to determine the respective MTPAs 2-5. After six weeks, the anonymized radiographs and photographs of the same feet without apparent affiliation were presented again. The terms "normal," "borderline normal," and "abnormal" were assigned by the observers. Viewers considered MTP-2 alignment from 0° to -20° to be normal, and below -30° abnormal; MTP-3, 0° to -15° to be normal and below -30° abnormal; MTP-4, 0° to -10° normal and below -20° abnormal. Between 5° valgus and 15° varus was the range of MTP-5 recognized as normal. High intra-observer but low interobserver reliability with overall low correlation of clinical and radiographic aspects was observed. The assessment of the terms "normal" or "abnormal" are subject to a high degree of variation. Therefore, these terms should be used cautiously.

Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery.

The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson's disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.