Integrated Compression Screw Stabilization of the Dorsal Lunate Facet in Intra-Articular Distal Radius Fractures.

PURPOSE: To evaluate outcomes of intra-articular distal radius fractures with displaced dorsal lunate facet fragments treated with a combination of volar plating and the use of a dorsal screw that integrates into the plate. METHODS: We reviewed a retrospective cohort of 22 patients who underwent open reduction and internal fixation of an intra-articular distal radius fracture with a volar plate in conjunction with the Frag-Loc Compression screw. Patient charts and radiographs were reviewed for clinical and radiographic outcomes. RESULTS: A total of 12 patients with a minimum 6-month follow-up who met all eligibility criteria were included in this study. There were 8 women and 4 men. The mean age was 55.2 years. Mean follow-up was 11.5 months (range, 6-21 months). The most common mechanism of injury was a fall from standing (75.0%). At final follow-up, all patients were able to return to their previous level of function. Bony union was achieved in all patients at the time of final follow-up. Average radiographic parameters at final follow-up were radial inclination 24.2° ± 5.3°, volar tilt 1.3° ± 5.2°, and ulnar variance 0.9 ± 1.7 mm. During the follow-up period, transient median nerve paresthesias were observed in 4 patients, with spontaneous resolution in 3 of 4 patients. Loss of articular reduction was not observed in any case. CONCLUSIONS: This study demonstrates satisfactory clinical and radiographic results and minimal complications with utilization of a new fixation device for distal radius fractures with displaced dorsal lunate facet fragments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

In Vivo Mechanical Function of the Distal Radial Ulnar Ligaments During Rotation of the Wrist.

PURPOSE: The purpose of this study was to investigate changes in length of the volar and dorsal radioulnar ligaments (VRULs and DRULs), and the distal radioulnar joint (DRUJ) space during unweighted and weighted rotation of the wrist using magnetic resonance imaging and biplanar fluoroscopy. METHODS: Fourteen wrists in 7 normal adult volunteers were imaged to define the 3-dimensional geometry of the DRUJ and the insertion sites of the superficial and deep bundles of the VRULs and DRULs. Subjects were imaged at 10 positions of forearm rotation ranging from full pronation to full supination, with or without a 5-pound weight. Lengths of the superficial and deep VRUL and DRUL bundles and DRUJ space were measured (in millimeters) at each position to evaluate ligament function and DRUJ stability. RESULTS: In the unweighted and weighted trials, maximal elongation of both deep and superficial VRUL bundles occurred in supination and maximal lengths of the deep and superficial DRUL bundles occurred in pronation. Maximum DRUJ space occurred during pronation and a minimum occurred in 30° of supination. In weighted trials, there was a significant increase in deep and superficial VRUL bundle length at positions between 30° of pronation and 30° of supination; however, there was no effect of weight on DRULs length. In weighted trials, there was a significant increase in DRUJ space at positions between full pronation and 15° of supination. CONCLUSIONS: This study demonstrates elongation of the VRULs in supination and the DRULs in pronation. There was no evidence of reciprocal loading of superficial/deep ligament bundles on either the dorsal or the volar aspects of the DRUJ. The effect of loading the wrist during rotation was apparent primarily in the VRULs, but not the DRULs. The DRUJ space was lowest at approximately 30° of supination. CLINICAL RELEVANCE: These results add information to the literature regarding the complicated biomechanics of the triangular fibrocartilage complex and DRUJ. Future work should evaluate changes in biomechanics caused by triangular fibrocartilage complex tears to determine how tear severity and location relate to clinical symptoms.

Analysis of complication rates following perioperative transfusion in shoulder arthroplasty.

BACKGROUND: Postoperative anemia requiring a blood transfusion is not uncommon following anatomic total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA). However, the potential complications in patients undergoing transfusion after shoulder arthroplasty remain unclear. The goal of this study was to examine the postoperative outcomes of patients receiving blood transfusions following TSA and RTSA. METHODS: Using the Medicare Standard Analytic Files database, we identified all patients undergoing TSA or RTSA between 2005 and 2010. Using International Classification of Diseases, Ninth Revision, Clinical Modification and Current Procedural Terminology codes, we identified the procedure, transfusion status, comorbidities, and postoperative complications of interest. Odds ratios and 95% confidence intervals were calculated. RESULTS: We identified 7,794 patients who received a perioperative blood transfusion following TSA or RTSA, as well as 34,293 age- and gender-matched controls, during the study period. Patients who received a perioperative transfusion had statistically significantly higher rates of myocardial infarction, pneumonia, systemic inflammatory response syndrome or sepsis, venous thromboembolic events, and cerebrovascular accidents at all time points in question. Patients who received a blood transfusion also showed an increased incidence of surgical complications, including periprosthetic infection and mechanical complications, up to 2 years postoperatively. CONCLUSION: To our knowledge, this represents the largest study to examine the relationship between the need for perioperative blood transfusion and postoperative medical and surgical outcomes following TSA and RTSA. The results observed in this study highlight the importance of preoperative counseling and medical optimization prior to shoulder arthroplasty, particularly in patients with preoperative anemia or multiple medical comorbidities.

Extraction-controlled terahertz frequency quantum cascade lasers with a diagonal LO-phonon extraction and injection stage.

We report an extraction-controlled terahertz (THz)-frequency quantum cascade laser design in which a diagonal LO-phonon scattering process is used to achieve efficient current injection into the upper laser level of each period and simultaneously extract electrons from the adjacent period. The effects of the diagonality of the radiative transition are investigated, and a design with a scaled oscillator strength of 0.45 is shown experimentally to provide the highest temperature performance. A 3.3 THz device processed into a double-metal waveguide configuration operated up to 123 K in pulsed mode, with a threshold current density of 1.3 kA/cm2 at 10 K. The QCL structures are modeled using an extended density matrix approach, and the large threshold current is attributed to parasitic current paths associated with the upper laser levels. The simplicity of this design makes it an ideal platform to investigate the scattering injection process.

Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors.

Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50=1.0 µM, cell IC50=1.8 µM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50=120 nM and cell potency to IC50=230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine.

Use of Liposomal Bupivacaine Instead of an Epidural Can Improve Outcomes Following Total Knee Arthroplasty.

The purpose of this study was to compare periarticular injection of liposomal bupivacaine (LB) to epidural analgesia as part of multimodal pain management strategy for total knee arthroplasty (TKA). A retrospective review of 50 patients undergoing TKA compared 25 patients who received LB to 25 patients who received an epidural. After postoperative day 1, patients who received LB exhibited significantly lower (p < .001) pain scores than those who received an epidural. Patients who received LB also had a significantly shorter length of hospital stay (p < .0001), greater range of motion on postoperative day 1, and walked significantly farther (p < .001) on postoperative day 1. LB appears to provide effective pain control leading to shorter hospital stays and improved early physical function compared with standard pain management with an epidural.

Comparison of Low-Dose Computed Tomography Versus Conventional-Dose Computed Tomography in the Evaluation of Distal Radius Fractures.

BACKGROUND: Distal radius fractures (DRFs) are common upper extremity fractures and often require surgical fixation when they are intraarticular. Preoperative computed tomography (CT) has emerged as a surgical planning tool to evaluate intraarticular DRFs. Although CT affords additional details, patients receive higher radiation doses than standard radiographs. We aim to develop a low-dose CT (LDCT) protocol, relative to the institutional standard-dose CT wrist for intraarticular DRFs although providing adequate detail for surgical decision-making. METHODS: A single-institution prospective study was conducted on patients with intraarticular DRFs who underwent closed reduction and below-elbow splinting who otherwise would undergo wrist CT. Observations were defined as total measurements taken, with each view undergoing 44 measurements. Patients underwent 2 scans with a standard dose and a 10× dose reduction. Articular step and gap measurements were recorded in the sagittal and coronal images. RESULTS: A total of 11 patients were enrolled (7 women and 4 men). The mean age was 55 years (SD = 20.1). There were a total of 4 reviewers: 1 attending surgeon, 2 resident physicians, and 1 student. When comparing LDCT and conventional-dose CT (CDCT), there were no significant differences in step and gap measurements across all reviewers. CONCLUSION: This study demonstrated that LDCT provides comparable imaging quality for surgical planning as a CDCT without significant diagnostic decay in the setting of DRFs. This comes with the added benefit of a 10-fold reduction in radiation exposure. These results suggest that LDCT is an opportunity to reduce effective radiation in patients although providing beneficial preoperative imaging.

A central review of histopathology reports after breast cancer neoadjuvant chemotherapy in the neo-tango trial.

BACKGROUND: Neo-tAnGo, a National Cancer Research Network (NCRN) multicentre randomised neoadjuvant chemotherapy trial in early breast cancer, enroled 831 patients in the United Kingdom. We report a central review of post-chemotherapy histopathology reports on the surgical specimens, to assess the presence and degree of response. METHODS: A central independent two-reader review (EP and HME) of histopathology reports from post-treatment surgical specimens was performed. The quality and completeness of pathology reporting across all centres was assessed. The reviews included pathological response to chemotherapy (pathological complete response (pCR); minimal residual disease (MRD); and lesser degrees of response), laterality, the number of axillary metastases and axillary nodes, and the type of surgery. A consensus was reached after discussion. RESULTS: In all, 825 surgical reports from 816 patients were available for review. Out of 4125 data items there were 347 discrepant results (8.4% of classifications), which involved 281 patients. These involved grading of breast response (169 but only 9 involving pCR vs MRD); laterality (6); presence of axillary metastasis (35); lymph node counts (108); and type of axillary surgery (29). Excluding cases with pCR, only 45% of reports included any comment regarding response in the breast and 30% in the axillary lymph nodes. CONCLUSION: We found considerable variability in the completeness of reporting of surgical specimens within this national neoadjuvant breast cancer trial. This highlights the need for consensus guidelines among trial groups on histopathology reporting, and the participation of histopathologists throughout the development and analysis of neoadjuvant trials.

Lifetime of the Bose gas with resonant interactions.

We study the lifetime of a Bose gas at and around unitarity using a Feshbach resonance in lithium 7. At unitarity, we measure the temperature dependence of the three-body decay coefficient L(3). Our data follow a L(3)=λ(3)/T(2) law with λ(3)=2.5(3)(stat)(6)(syst)×10(-20) (µK)(2) cm(6) s(-1) and are in good agreement with our analytical result based on zero-range theory. Varying the scattering length a at fixed temperature, we investigate the crossover between the finite-temperature unitary region and the previously studied regime where |a| is smaller than the thermal wavelength. We find that L(3) is continuous across the resonance, and over the whole a<0 range our data quantitatively agree with our calculation.

Impact of Time to Fixation on Outcomes of Operative Treatment of Intra-articular Distal Radius Fractures.

BACKGROUND: The incidence of operative treatment of distal radius fractures (DRFs) has increased recently, but the optimal timing for surgical fixation remains unclear. We hypothesized that: (1) an increase in time to fixation of intra-articular DRFs would increase the likelihood of postoperative complications; and (2) increased time from injury to fixation would lead to longer surgical time and worse range of motion (ROM) outcomes. METHODS: We retrospectively reviewed 299 fractures in 284 adult patients who underwent open reduction and internal fixation (ORIF) of a closed, intra-articular DRF at our institution over a 10.5-year period. Demographic information, time to surgery (TTS) from injury, surgical time, tourniquet time, complications, and final postoperative ROM were collected for logistic regression modeling to predict the risk of postoperative complication. RESULTS: Twenty-seven (9.0%) patients experienced postoperative complications. The median TTS (Q1-Q3) for all patients was 7.0 (4.0-12.0) days. Patients who experienced an early postoperative complication had significantly longer median TTS (10.0 days) than those who did not (7.0 days). Patients with longer TTS were more likely to experience a complication (odds ratio, 1.11; 95% confidence interval, 1.04-1.19; P = .006). Tourniquet time and final wrist ROM were not related to TTS. A logistic regression analysis found that early complication rate doubles at 7.0 days after injury (from 3.5% to 6.9%). CONCLUSIONS: Patients with operative intra-articular distal radius fractures should ideally be fixed within 7 to 10 days of injury to minimize the risk of early postoperative complications. The tourniquet time and final ROM were not associated with time to surgery.

Suspensionplasty for Revision Thumb Carpometacarpal Osteoarthritis Surgery: Comparing Suture Button Suspensionplasty to Ligament Reconstruction and Tendon Interposition.

SUMMARY: Several surgical procedures have been described to treat thumb carpometacarpal osteoarthritis, including suture button suspensionplasty and ligament reconstruction and tendon interposition. To date, no single procedure has demonstrated clinical superiority. Suture button suspensionplasty has achieved favorable outcomes at 5 years in primary cases, but has not been validated in revision surgery. In this study, it was evaluated for revision of failed thumb carpometacarpal osteoarthritis surgery, and outcomes were compared to ligament reconstruction and tendon interposition outcomes. A retrospective chart review identified patients who underwent suture button suspensionplasty or ligament reconstruction and tendon interposition after failure of previous thumb carpometacarpal osteoarthritis surgery since 2010. Eighteen patients were included, with nine patients in each group. Eighteen patients had mean final follow-up of 35 months. There were two complications in the ligament reconstruction and tendon interposition group and none in the suture button suspensionplasty group. No patients required additional surgery. The suture button suspensionplasty group had an average visual analogue scale pain score improvement of 2.9, compared to 2.4 in the ligament reconstruction and tendon interposition group. Average final Quick Disabilities of the Arms, Shoulder and Hand questionnaire score was 15.1 in the suture button suspensionplasty group, compared to 22.6 in the ligament reconstruction and tendon interposition group. Mean operative time of 86.3 minutes in the suture button suspensionplasty group was significantly shorter than the 121-minute mean in the ligament reconstruction and tendon interposition group. Suture button suspensionplasty is an effective treatment option for revision of previous thumb carpometacarpal osteoarthritis surgery, with outcomes comparable to revision using ligament reconstruction and tendon interposition, and the added benefit of shorter operative times and early mobilization. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Oral Microbiota Composition Predicts Early Childhood Caries Onset.

As the most common chronic disease in preschool children in the United States, early childhood caries (ECC) has a profound impact on a child's quality of life, represents a tremendous human and economic burden to society, and disproportionately affects those living in poverty. Caries risk assessment (CRA) is a critical component of ECC management, yet the accuracy, consistency, reproducibility, and longitudinal validation of the available risk assessment techniques are lacking. Molecular and microbial biomarkers represent a potential source for accurate and reliable dental caries risk and onset. Next-generation nucleotide-sequencing technology has made it feasible to profile the composition of the oral microbiota. In the present study, 16S ribosomal RNA (rRNA) gene sequencing was applied to saliva samples that were collected at 6-mo intervals for 24 mo from a subset of 56 initially caries-free children from an ongoing cohort of 189 children, aged 1 to 3 y, over the 2-y study period; 36 children developed ECC and 20 remained caries free. Analyses from machine learning models of microbiota composition, across the study period, distinguished between affected and nonaffected groups at the time of their initial study visits with an area under the receiver operating characteristic curve (AUC) of 0.71 and discriminated ECC-converted from healthy controls at the visit immediately preceding ECC diagnosis with an AUC of 0.89, as assessed by nested cross-validation. Rothia mucilaginosa, Streptococcus sp., and Veillonella parvula were selected as important discriminatory features in all models and represent biomarkers of risk for ECC onset. These findings indicate that oral microbiota as profiled by high-throughput 16S rRNA gene sequencing is predictive of ECC onset.

Identifying Factors Most Important to Lower Extremity Trauma Patients: Key Concepts from the Development of a Patient-Reported Outcome Instrument for Lower Extremity Trauma, The LIMB-Q.

BACKGROUND: Severe lower extremity injuries are challenging to treat. The aspects of limb salvage and amputation most important to patients are not well-defined. This study's aim is to develop a conceptual framework for a patient-reported outcome instrument for lower extremity trauma patients, by defining issues and concepts most important to this patient population. METHODS: This is an interpretative description of transcripts collected from semistructured qualitative interviews at a single institution. High-energy lower extremity trauma patients were recruited by means of purposeful sampling to maximize variability. Thirty-three participant interviews were needed to reach content saturation. These participants were aged 19 to 79 years; 21 were men (63.6 percent); participation was after reconstruction [n= 15 (45.5 percent)], after amputation [n = 11 (33.3 percent)], or after amputation after failed reconstruction [n = 7 (21.2 percent)]. Interviews were recorded, transcribed, and coded line-by-line. Concepts were labeled with major and minor themes and refined through a process of constant comparison. Analysis led to the development of a conceptual framework and item pool to inform the development of a patient-reported outcome measure. RESULTS: In total, 2430 unique codes were identified and used to generate the conceptual framework covering 10 major themes: appearance, environment, finances, physical, process of care, prosthesis, psychological, sexual, social, and treatment. CONCLUSIONS: This study establishes a comprehensive set of concepts, identifying what is most important to severe lower extremity trauma patients. These findings can be used to inform and focus research and clinical care, and provides the framework to develop a lower extremity trauma-specific patient-reported outcome instrument: the LIMB-Q.

Scalable synthesis and isolation of the four stereoisomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate, useful intermediates for the synthesis of S1P1 receptor agonists.

The individual isomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate are useful intermediates for the synthesis of S1P1 receptor agonists. Herein we describe a scalable synthesis and isolation of each of the four stereoisomers of this compound in gram quantities with >98% ee and de. The utility of this approach is demonstrated by the synthesis of ((1R,3R)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol in 7 steps, 11% overall yield, and >98% ee and de.

Patient-reported Outcome Instruments in Lower Extremity Trauma: A Systematic Review of the Literature.

BACKGROUND: Advances in fracture fixation and soft tissue coverage continue to improve the care of patients after limb-threatening lower extremity (LE) trauma. However, debate continues regarding which treatment option-reconstruction or amputation-is most appropriate. Many authors have attempted to quantify the patient experience in this treatment paradigm; however, they have not used patient-reported outcome (PRO) instruments specific to this population. Our aim was to identify and evaluate PRO instruments developed specifically for LE trauma, applicable to reconstruction and amputation, using established PRO instrument development and validation guidelines. METHODS: A multidisciplinary team used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method to query PubMed, Medline Ovid, EMBASE, Cochrane, Medline Web of Science, and Psych Info databases from inception to November 2016. Publications were included that described the development and/or validation of a PRO instrument assessing satisfaction and/or quality of life in LE trauma, applicable to both amputation and reconstruction. Two authors independently reviewed each full-text citation. RESULTS: After removing duplicates, 6,290 abstracts were identified via the database query. Following a preliminary title and abstract screen, 657 full-text citations were reviewed. Of these references, none satisfied the previously established inclusion criteria. CONCLUSIONS: No studies were identified that described a PRO instrument developed to assess outcomes in LE trauma patients applicable to both reconstruction and amputation. There is thus a need for a PRO instrument designed specifically for patients who have sustained limb-threatening LE trauma to guide treatment decisions.

Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3.

Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in compounds with improved in-vitro species selectivity. Incorporation of an 8-quinoline amide and conformational rigidification of an aliphatic tether furnished potent compounds suitable for further lead optimization.

Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3.

High-throughput screening identified a low molecular weight antagonist of CXCR3 displaying micromolar activity in a membrane filtration-binding assay. Systematic modification of the benzimidazole core and tethered acetophenone moiety established tractable SAR of analogs with improved physicochemical properties and sub-micromolar activity across both human and murine receptors.

Association between Oral Candida and Bacteriome in Children with Severe ECC.

Candida albicans is an opportunistic fungal organism frequently detected in the oral cavity of children with severe early childhood caries (S-ECC). Previous studies suggested the cariogenic potential of C. albicans, in vitro and in vivo, and further demonstrated its synergistic interactions with Streptococcus mutans. In combination, the 2 organisms are associated with higher caries severity in a rodent model. However, it remains unknown whether C. albicans influences the composition and diversity of the entire oral bacterial community to promote S-ECC onset. With 16s rRNA amplicon sequencing, this study analyzed the microbiota of saliva and supragingival plaque from 39 children (21 S-ECC and 18 caries-free [CF]) and 33 mothers (17 S-ECC and 16 CF). The results revealed that the presence of oral C. albicans is associated with a highly acidogenic and acid-tolerant bacterial community in S-ECC, with an increased abundance of plaque Streptococcus (particularly S. mutans) and certain Lactobacillus/Scardovia species and salivary/plaque Veillonella and Prevotella, as well as decreased levels of salivary/plaque Actinomyces. Concurrent with this microbial community assembly, the activity of glucosyltransferases (cariogenic virulence factors secreted by S. mutans) in plaque was significantly elevated when C. albicans was present. Moreover, the oral microbial community composition and diversity differed significantly by disease group (CF vs. S-ECC) and sample source (saliva vs. plaque). Children and mothers within the CF and S-ECC groups shared microbiota composition and diversity, suggesting a strong maternal influence on children's oral microbiota. Altogether, this study underscores the importance of C. albicans in association with the oral bacteriome in the context of S-ECC etiopathogenesis. Further longitudinal studies are warranted to examine how fungal-bacterial interactions modulate the onset and severity of S-ECC, potentially leading to novel anticaries treatments that address fungal contributions.

Identifying Predictors of Time to Soft-Tissue Reconstruction following Open Tibia Fractures.

BACKGROUND: Controversy remains regarding the optimal timing of soft-tissue coverage following severe lower extremity trauma. This study identifies nationwide practice patterns and factors associated with discrepancies in time to first flap surgery following open tibia fractures. METHODS: A retrospective analysis was performed on the National Trauma Databank from 2008 to 2015 to identify patients who presented with an open tibia fracture and underwent subsequent flap reconstruction. A least absolute shrinkage and selection operator algorithm was performed, revealing those factors most significantly associated with differences in time to flap surgery from hospitalization. RESULTS: A total of 3297 patients were included in the analysis. Mean ± SD and median times to first flap surgery were 230.1 ± 246.7 hours and 169.1 hours, respectively. Older age, nonwhite race, treatment in the South, and non-private insurance status were all independently associated with an increased time to flap surgery. In addition, more surgical débridements; a higher Injury Severity Score and/or Abbreviated Injury Scale score; and a nerve, vascular, and/or crush injury were independent predictors of an increased time to flap surgery. CONCLUSIONS: Most patients who present with open tibia fractures requiring soft-tissue coverage undergo flap reconstruction after the historical 72-hour window. Specific sociodemographic and clinical factors were independently predictive of an increased time to flap surgery. These findings suggest that not all patients in the United States are receiving the same level of care in lower extremity trauma reconstruction, emphasizing the need to develop more explicit national standards. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Susceptibility to fluorescent light-induced chromatid breaks associated with DNA repair deficiency and malignant transformation in culture.

The increased susceptibility of mouse cells to fluorescent light-induced chromatid damage following their spontaneous malignant transformation in culture could result from loss or inactivation of catalase that decomposes the photoproduct H2O2 or from impaired capacities to repair DNA damage. No consistent change in catalase activity with respect to neoplastic state could be established. To interpret the cytogenetic damage in terms of DNA strand breaks, we determined the incidence of chromatid breaks induced by light exposure during the G1 and late S-G2 phases of the cell cycle in normal and malignant derivatives of a C3H mouse cell line. Chromatid breaks at metaphase following light exposure during G1 would result from DNA strand breaks, cross-links, or base damage, whereas breaks following exposure during late S-G2 would result from single-or double-strand breaks. Both G1 and late S-G2 were susceptible in malignant cells but only G1 in normal. Since caffeine inhibits DNA repair, we compared its effects on light-induced chromatid damage in the normal and malignant cells to assess their DNA repair capacities. Treatment of normal cells with caffeine (50 microgram/ml) directly following five hr of light exposure in G1 increased the chromatid damage to that in malignant cells exposed with or without caffeine. Similarly, treatment of normal cells with caffeine during late S-G2 exposure increased chromatid damage to a level not significantly different from that in malignant cells exposed without caffeine. Caffeine had little influence on chromatid damage in malignant cells. The increased susceptibility of malignant mouse cells to fluorescent light-induced chromatid breaks thus appears to result from impaired capacities to repair DNA damage.