Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy.

Standard-of-care treatment regimens have long been designed for maximal cell killing, yet these strategies often fail when applied to metastatic cancers due to the emergence of drug resistance. Adaptive treatment strategies have been developed as an alternative approach, dynamically adjusting treatment to suppress the growth of treatment-resistant populations and thereby delay, or even prevent, tumor progression. Promising clinical results in prostate cancer indicate the potential to optimize adaptive treatment protocols. Here, we applied deep reinforcement learning (DRL) to guide adaptive drug scheduling and demonstrated that these treatment schedules can outperform the current adaptive protocols in a mathematical model calibrated to prostate cancer dynamics, more than doubling the time to progression. The DRL strategies were robust to patient variability, including both tumor dynamics and clinical monitoring schedules. The DRL framework could produce interpretable, adaptive strategies based on a single tumor burden threshold, replicating and informing optimal treatment strategies. The DRL framework had no knowledge of the underlying mathematical tumor model, demonstrating the capability of DRL to help develop treatment strategies in novel or complex settings. Finally, a proposed five-step pathway, which combined mechanistic modeling with the DRL framework and integrated conventional tools to improve interpretability compared with traditional "black-box" DRL models, could allow translation of this approach to the clinic. Overall, the proposed framework generated personalized treatment schedules that consistently outperformed clinical standard-of-care protocols. SIGNIFICANCE: Generation of interpretable and personalized adaptive treatment schedules using a deep reinforcement framework that interacts with a virtual patient model overcomes the limitations of standardized strategies caused by heterogeneous treatment responses.

Peri-articular elbow fracture fixations with magnesium implants and a review of current literature: A case series.

BACKGROUND: In recent years, the use of Magnesium alloy implants have gained renewed popularity, especially after the first commercially available Conformité Européenne approved Magnesium implant became available (MAGNEZIX® CS, Syntellix) in 2013. AIM: To document our clinical and radiographical outcomes using magnesium implants in treating peri-articular elbow fractures. METHODS: Our paper was based on a retrospective case series design. Intra-operatively, a standardized surgical technique was utilized for insertion of the magnesium implants. Post - operatively, clinic visits were standardized and physical exam findings, functional scores, and radiographs were obtained at each visit. All complications were recorded. RESULTS: Five patients with 6 fractures were recruited (2 coronoid, 3 radial head and 1 capitellum). The mean patient age and length of follow up was 54.6 years and 11 months respectively. All fractures healed, and none exhibited loss of reduction or complications requiring revision surgery. No patient developed synovitis of the elbow joint or suffered electrolytic reactions when titanium implants were used concurrently. CONCLUSION: Although there is still a paucity of literature available on the subject and further studies are required, magnesium implants appear to be a feasible tool for fixation of peri-articular elbow fractures with promising results in our series.

Diabetic foot in primary and tertiary (DEFINITE) Care: A health services innovation in coordination of diabetic foot ulcer (DFU) Care within a healthcare cluster - 18-month results from an observational population health cohort study.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional and multi-disciplinary team (MDT) health systems innovation programme at a healthcare cluster in Singapore. We aim to achieve coordinated MDT care across primary and tertiary care for patients with diabetic foot ulcers (DFU), within our public healthcare cluster - an integrated network of seven primary care polyclinics and two acute care tertiary hospitals (1700-bed and 800-bed) with a total catchment population of 2.2 million residents. Results from prospective DEFINITE Care is referenced against a retrospective 2013-2017 cohort, which was previously published. Cardiovascular profile of the study population is compared against the same population's profile in the preceding 12 months. Between June 2020 and December 2021, there were 3475 unique patients with DFU with mean age at 65.9 years, 61.2% male, mean baseline HbA1c at 8.3% with mean diabetes duration at 13.3 years, mean diabetes complication severity index (DCSI) at 5.6 and mean Charlson Comorbidity Index (CCI) at 6.8. In the 12-months preceding enrolment to DEFINITE Care, 35.5% had surgical foot debridement, 21.2% had minor lower extremity amputation (LEA), 7.5% had major LEA whilst 16.8% had revascularisation procedures. At 18-months after the implementation of DEFINITE Care programme, the absolute minor and major amputation rates were 8.7% (n = 302) and 5.1% (n = 176), respectively, equating to a minor and major LEA per 100000 population at 13.7 and 8.0, respectively. This represents an 80% reduction in minor amputation rates (P < .001) and a 35% reduction in major amputation rates (P = .005) when referenced against a retrospective 2013-2017 cohort, which had minor and major LEA per 100000 population at 68.9 and 12.4, respectively. As compared to the preceding 12 months, there was also a significant improvement in cardiovascular profile (glycemic and lipid control) within the DEFINITE population, with improved mean HbAc1 (7.9% from 8.4%, P < .001), low-density lipoprotein (LDL) levels (2.1 mmol/L from 2.2, P < .001), total cholesterol (3.9 mmol/L from 4.1, P < .001) and triglycerides levels (1.6 mmol/L from 1.8, P = .002). Multivariate analysis revealed a history of minor amputation in the preceding 12 months to be an independent predictor for major and minor amputation within the study period of 18 months (Hazard Ratio 3.4 and 1.8, respectively, P < .001). In conclusion, within DEFINITE care, 18-month data showed a significant reduction of minor and major LEA rates, with improved medical optimisation and cardiovascular profile within the study population.

Mortality rates for hip fracture patients managed surgically and conservatively in a dedicated unit in Singapore.

INTRODUCTION: At our hospital, an unusually high proportion of patients and families opted for conservative management of hip fractures. This study aimed to compare the mortality rates of patients with hip fractures treated conservatively to that of operatively managed patients in a dedicated hip fracture unit. MATERIALS AND METHODS: Retrospective analysis was done for patients who were treated for hip fractures between January 2015 and October 2017 in a Hip Fracture Unit at a tertiary hospital. Patients were managed non-operatively or surgically after discussion with the multi-disciplinary team. RESULTS: 233 patients were treated conservatively and 781 underwent operative management for hip fractures. Patients managed non-operatively had a higher inpatient, 30-day and 1-year mortality rates. Inpatient mortality was 6.01% for conservatively managed compared to 0% for operative management. 30-day mortality for conservatively managed patients was 8.58% as compared to 0% for operatively managed patients, and 1-year mortality was 33.05% as opposed to 8.96%. There was an association seen with the type of management of hip fractures and that of inpatient death (p = 0.000), death in 30 days (p = 0.000) and death in 1 year (p = 0.000). The type of management was a predictive factor in 1-year mortality (p = 0.000). The average number of co-morbidities in conservatively managed patients was 5.2 compared to surgically managed patients of 4.0. Conservatively managed hip patients had a higher prevalence of stroke, chronic kidney disease and ischemic heart disease. Complications during hospital stay were comparable for both groups. The mean length of hospital stay was similar for both groups. CONCLUSION: Surgical intervention for hip fractures is associated with lower inpatient, 30-day and 1-year mortality rates. However, patient co-morbidities and pre-morbid conditions should also be considered. LEVEL OF EVIDENCE: IV.

Disseminated intravascular coagulation following femoral nailing in a metastatic prostate carcinoma patient - A case report.

INTRODUCTION: Disseminated intravascular coagulation (DIC) is a rare condition that is known to affect patients with metastatic prostate adenocarcinoma. In an unsuspecting orthopaedic surgeon, DIC could lead to significant morbidity and mortality. This article highlights another such case and discusses management strategies to help improve clinical outcomes for these patients. CASE: A 70-year-old male with metastatic prostate adenocarcinoma underwent prophylactic intramedullary nailing of an impending right femur pathological fracture. Surgery was uneventful, however postoperatively he was haemodynamically unstable with heavily soaked dressings. Laboratory investigations revealed DIC. Supportive treatment and correction of coagulopathy were undertaken. Ketoconazole was also initiated by Urology Services to treat the underlying condition of metastatic prostate carcinoma. Unfortunately, the patient responded poorly and passed away. CONCLUSION: DIC is rarely encountered in orthopaedic surgery, but carries significant morbidity and mortality risks. Patients with risk factors, in particular metastatic cancer, should be screened for non-overt pre-DIC state and coagulopathies corrected preoperatively. Initiating treatment of underlying condition can be considered preoperatively in established non-overt DIC. Operative technique can also be modified to minimise risk of fat or tumour emboli. Early recognition, prompt resuscitation and timely treatment of underlying condition may be able to improve the outcomes in these patients.

The management of concomitant septic arthritis of the knee and femoral osteomyelitis - A case series and literature review.

We present a case series comprising three patients with concomitant septic arthritis of the knee and osteomyelitis of the femur. Early advanced imaging rendered the accurate diagnosis of the condition and the appropriate surgical approach and technique used to treat the infection. Repeated extensive surgical debridement, irrigation and insertion of antibiotic-impregnated cement rod into the femur were required, in addition to long term antibiotics. The infection in all three cases was eradicated successfully. Following a period of physical rehabilitation, they had fairly preserved independent ambulatory function. We advocate a high index of suspicion of this condition with subsequent early advanced imaging for a timely diagnosis. In addition, we described our challenges in the fabrication process of the antibiotic-impregnated cement rod.

Return to work after surgically treated acetabular fractures in an Asian population.

BACKGROUND: Acetabular fractures are rare but are severe injuries that occur in younger patients with a significant economic impact. There is limited evidence describing the return to work rates in this group of patients. The aim of our study was to examine the rate and time to return to work (RTW) after surgical fixation of acetabular fractures. METHODS: We performed a retrospective study on all patients with surgically treated acetabular fractures at a single institution between 1 July 2010 and 31 December 2018. Medical records were reviewed to analyze demographics such as age, gender, occupation and RTW characteristics. RESULTS: There were 30 patients, with a mean age of 43.3 ± 12.7 years. There were 26 patients who were employed prior to injury. The most common mechanism of injury was from a road traffic accident (73.3%). The average ISS was 8.9 ± 5.2. The mean follow-up duration was 21.5 months ± 15.7. The rate of RTW was 80.8%. Eighteen patients (85.7%) returned to the same job and duties, while two (9.5%) returned with same job but lighter duties and one (4.8%) had to change job. Three patients (11.5%) retired. The average time to return to work was 8.3 months (range 2-57.5). RTW rates were 15.4%, 61.5%, 69.2% at 3, 6 and 12 months, respectively. CONCLUSION: Acetabular fractures can lead to loss of economic productivity, with 80.8% of patients returning to work. Work reintegration programs after acetabular fractures are important.

Risk factors for mechanical failure of intertrochanteric fractures after fixation with proximal femoral nail antirotation (PFNA II): a study in a Southeast Asian population.

INTRODUCTION: Intertrochanteric hip fractures pose a significant health problem. The proximal femur nail anti-rotation (PFNA IIDePuySynthes) is the most commonly used implant for intramedullary nailing of unstable intertrochanteric fractures at our institution. We aim to identify the risk factors predisposing to mechanical failure of intertrochanteric hip fractures fixation with PFNAII in our Southeast Asian population. MATERIALS AND METHODS: We retrospectively reviewed 295 consecutive patients who underwent PFNA fixation for intertrochanteric fractures of the proximal femur between January 2014 and June 2018 at our institution. Exclusion criteria included a follow-up period of less than 4 months and patients with polytrauma. 204 patients were eligible for analysis, of which 22 had mechanical failure of PFNAII. We compared these patients with respect to their demographics, medical co-morbidities, quality of reduction according to the Baumgartner scale, calcar restoration, blade position according to Cleveland Zones, the stability of fracture according to OTA/AO classification, neck-shaft-angle, tip-apex distance, as well as neck of femur bone mineral density T-score. Patients were followed up for a minimum of 4 months and until fracture union or complication had occurred. Logistic regression analysis was performed to determine the odds ratio for mechanical failure for selected variables. RESULTS: Good quality of reduction reduced risk of mechanical failure whilst posterior blade position in lateral hip X-ray predicted it, with odds ratios of 0.147 (95% confidence interval, 0.030-0.733; p = 0.019) and12.12 (95% confidence interval, 1.583-92.825; p = 0.016) respectively. On univariate analysis, the mechanical failure group were older, had poorer calcar restoration, more unstable fracture patterns, more varus neck-shaft angle, and trochanteric starting points that were lateral to or on the tip of the greater trochanter. However, these were not significant in multivariate analysis. Tip apex distance, the severity of osteoporosis, presence of diabetes, chronic kidney disease and serum vitamin D levels were not significant predictors of failure. CONCLUSIONS: To avoid mechanical failure, one should aim to achieve a good quality of reduction and centre blade position on lateral hip X-ray. Tip apex distance did not predict mechanical failure in our study.

Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and RAS Mutations.

Background:RAS gene family mutations are the most prevalent in thyroid nodules with indeterminate cytology and are present in a wide spectrum of histological diagnoses. We evaluated differentially expressed genes and signaling pathways across the histological/clinical spectrum of RAS-mutant nodules to determine key molecular determinants associated with a high risk of malignancy. Methods: Sixty-one thyroid nodules with RAS mutations were identified. Based on the histological diagnosis and biological behavior, the nodules were grouped into five categories indicating their degree of malignancy: non-neoplastic appearance, benign neoplasm, indeterminate malignant potential, low-risk cancer, or high-risk cancer. Gene expression profiles of these nodules were determined using the NanoString PanCancer Pathways and IO 360 Panels, and Angiopoietin-2 level was determined by immunohistochemical staining. Results: The analysis of differentially expressed genes using the five categories as supervising parameters unearthed a significant correlation between the degree of malignancy and genes involved in cell cycle and apoptosis (BAX, CCNE2, CDKN2A, CDKN2B, CHEK1, E2F1, GSK3B, NFKB1, and PRKAR2A), PI3K pathway (CCNE2, CSF3, GSKB3, NFKB1, PPP2R2C, and SGK2), and stromal factors (ANGPT2 and DLL4). The expression of Angiopoietin-2 by immunohistochemistry also showed the same trend of increasing expression from non-neoplastic appearance to high-risk cancer (p < 0.0001). Conclusions: The gene expression analysis of RAS-mutant thyroid nodules suggests increasing upregulation of key oncogenic pathways depending on their degree of malignancy and supports the concept of a stepwise progression. The utility of ANGPT2 expression as a potential diagnostic biomarker warrants further evaluation.

Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies.

Deaths from cancer are mostly due to metastatic disease that becomes resistant to therapy. A mainstay treatment for many cancers is chemotherapy, for which the dosing strategy is primarily limited by patient toxicity. While this MTD approach builds upon the intuitively appealing principle that maximum therapeutic benefit is achieved by killing the largest possible number of cancer cells, there is increasing evidence that moderation might allow host-specific features to contribute to success. We believe that a "Goldilocks Window" of submaximal chemotherapy will yield improved overall outcomes. This window combines the complex interplay of cancer cell death, immune activity, emergence of chemoresistance, and metastatic dissemination. These multiple activities driven by chemotherapy have tradeoffs that depend on the specific agents used as well as their dosing levels and schedule. Here we present evidence supporting the idea that MTD may not always be the best approach and offer suggestions toward a more personalized treatment regime that integrates insights into patient-specific eco-evolutionary dynamics.

Cephalomedullary blade cut-ins: a poorly understood phenomenon.

OBJECTIVES: Proximal femoral nail antirotation (PFNA) cut-in is a unique phenomenon seen in pertrochanteric hip fractures treated with the PFNA. Cut-in refers to the superomedial migration of the proximal femoral blade into the femoral head and hip joint. We recognize that cut-in is a completely separate entity from the well-described cut-out failure. This study assesses relevant radiological and patient risks factors for cut-in. DESIGN: Retrospective multicenter study looking at patients with pertrochanteric hip fractures managed with the Synthes PFNA SETTING: Four tertiary hospitals over 7 years. PATIENTS: Patients with cut-ins were identified. OUTCOME MEASUREMENT: The radiological appearance of this mode of failure was assessed and compared to cut-outs. Patient demographics, fracture configuration, time to implant failure (cut-in), bone mineral density, tip-apex distance, neck-shaft angle and position of the tip of the helical blade in the femoral head were collected. RESULTS: There was a total of 1027 patients across 4 institutions with 23 patients with cut-in. Average neck-shaft angle was 133 degrees. 16 out of 19 patients had severe osteoporosis with BMD < - 2.5. 14 of 23 patients had poor placement of the blade. 13 of 23 had a tip-apex distance of more than 20 mm. CONCLUSION: We propose a standardized nomenclature of "cut-in" for the phenomenon of superomedial migration of the proximal femoral blade. An anatomical neck-shaft reduction, accurate blade placement and increased surveillance for patients with severe osteoporosis are required to reduce the incidence and morbidity of cut-in.

The Goldilocks Window of Personalized Chemotherapy: Getting the Immune Response Just Right.

The immune system is a robust and often untapped accomplice of many standard cancer therapies. A majority of tumors exist in a state of immune tolerance where the patient's immune system has become insensitive to the cancer cells. Because of its lymphodepleting effects, chemotherapy has the potential to break this tolerance. To investigate this, we created a mathematical modeling framework of tumor-immune dynamics. Our results suggest that optimal chemotherapy scheduling must balance two opposing objectives: maximizing tumor reduction while preserving patient immune function. Successful treatment requires therapy to operate in a "Goldilocks Window" where patient immune health is not overly compromised. By keeping therapy "just right," we show that the synergistic effects of immune activation and chemotherapy can maximize tumor reduction and control. SIGNIFICANCE: To maximize the synergy between chemotherapy and antitumor immune response, lymphodepleting therapy must be balanced in a "Goldilocks Window" of optimal dosing.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/20/5302/F1.large.jpg.

Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation.

Clonal hematopoiesis of indeterminate potential (CHIP) is a recently identified process where older patients accumulate distinct subclones defined by recurring somatic mutations in hematopoietic stem cells. CHIP's implications for stem cell transplantation have been harder to identify due to the high degree of mutational heterogeneity that is present within the genetically distinct subclones. In order to gain a better understanding of CHIP and the impact of clonal dynamics on transplantation outcomes, we created a mathematical model of clonal competition dynamics. Our analyses highlight the importance of understanding competition intensity between healthy and mutant clones. Importantly, we highlight the risk that CHIP poses in leading to dominance of precancerous mutant clones and the risk of donor derived leukemia. Furthermore, we estimate the degree of competition intensity and bone marrow niche decline in mice during aging by using our modeling framework. Together, our work highlights the importance of better characterizing the ecological and clonal composition in hematopoietic donor populations at the time of stem cell transplantation.

The Immune Checkpoint Kick Start: Optimization of Neoadjuvant Combination Therapy Using Game Theory.

PURPOSE: In an upcoming clinical trial at the Moffitt Cancer Center for women with stage 2/3 estrogen receptor-positive breast cancer, treatment with an aromatase inhibitor and a PD-L1 checkpoint inhibitor combination will be investigated to lower a preoperative endocrine prognostic index (PEPI) that correlates with relapse-free survival. PEPI is fundamentally a static index, measured at the end of neoadjuvant therapy before surgery. We have developed a mathematical model of the essential components of the PEPI score to identify successful combination therapy regimens that minimize tumor burden and metastatic potential, on the basis of time-dependent trade-offs in the system. METHODS: We considered two molecular traits, CCR7 and PD-L1, which correlate with treatment response and increased metastatic risk. We used a matrix game model with the four phenotypic strategies to examine the frequency-dependent interactions of cancer cells. This game was embedded in an ecological model of tumor population-growth dynamics. The resulting model predicts evolutionary and ecological dynamics that track with changes in the PEPI score. RESULTS: We considered various treatment regimens on the basis of combinations of the two therapies with drug holidays. By considering the trade off between tumor burden and metastatic potential, the optimal therapy plan was a 1-month kick start of the immune checkpoint inhibitor followed by 5 months of continuous combination therapy. Relative to a protocol giving both therapeutics together from the start, this delayed regimen resulted in transient suboptimal tumor regression while maintaining a phenotypic constitution that is more amenable to fast tumor regression for the final 5 months of therapy. CONCLUSION: The mathematical model provides a useful abstraction of clinical intuition, enabling hypothesis generation and testing of clinical assumptions.

A Comparison of Two Designs of Postoperative Shoe on Function, Satisfaction, and Back Pain After Hallux Valgus Surgery.

Background. The reverse camber shoe is commonly used after hallux valgus corrective surgery to offload the forefoot but is associated with back pain and poor compliance. Recent designs of postoperative shoes may obviate the need for a reverse camber. The purpose of this study was to compare the effects of a reverse camber shoe and a noncambered shoe with transitional rigidity after hallux valgus correction. Methods. A cohort of 80 feet was prospectively studied undergoing surgery at a single NHS trust. The first 40 feet received the reverse cambered Jura Medical Off-loader Heel shoe and the subsequent 40 feet received the noncambered DonJoy Podalux shoe. No demographic differences existed between the groups and data were collected at 2 weeks, 6 weeks, and 6 months. The Manchester-Oxford Foot Questionnaire (MOXFQ), a 5-question survey and dichotomous question about back pain was used to assess clinical outcome and radiographs were reviewed by 2 orthopaedic surgeons to monitor for loss of correction. Results. Both groups experienced comparable improvements in MOXFQ and shoe satisfaction from 2 weeks compared with 6 weeks. Six patients experienced back pain in the reverse cambered shoe group and none in the noncambered shoe group. Five patients stopped using the reverse cambered shoe during the first 6 weeks after surgery and none stopped using their prescribed noncambered shoe. No loss of corrections were observed in either group. Conclusion. Both shoe designs gave equal foot specific functional and radiological outcomes, but the noncambered shoe with transitional rigidity was associated with less back pain and better compliance. Levels of Evidence: Level II: Prospective comparative study.

Cadaveric experiments to evaluate pressure wave generated by radial shockwave treatment of plantar fasciitis.

BACKGROUND: Shockwave treatment is increasingly used for plantar fasciitis and Achilles tendinopathy. To be effective it is believed that high pressure must be achieved in the tissues. We report on the first human cadaveric experiments to characterize pressure from radial shockwave therapy (rSWT) for plantar fasciitis. METHODS: The pressure from rSWT was measured in two cadaveric feet using a needle hydrophone. Maximal pressure and energy flux were calculated from the measurements. RESULTS: The pressure persisted longer than supposed, for up to 400µs. The peak negative pressure was up to two Mega Pascal. The predicted energy in the tissue strongly depended on the time interval used in calculations. CONCLUSIONS: The measured pressure may be sufficiently high to cause cavitation in the tissue, which is one of the proposed healing mechanisms associated with rSWT. The results suggest that the energy is imparted to the tissues for much longer than previously thought.

A Retrospective Study Comparing Crossed and Lateral Wire Configurations in Paediatric Supracondylar Fractures.

BACKGROUND: Supracondylar fractures are common in children and are associated with significant morbidity. The purpose of our study was to assess and compare the clinical and radiological outcome of management of supracondylar fractures by both wire configurations, along with identifying factors that predispose to complications. MATERIALS & METHODS: We retrospectively reviewed all paediatric cases admitted with a supracondylar fracture over a five year period. We reviewed case notes, theatre records and radiographs to determine the age of the patient, classification of fracture, treatment method, delay to theatre, duration of surgery, wire configuration, Baumann´s angle, radiocapitellar alignment, anterior humeral alignment and complications. RESULTS: During the five year period we admitted 132 patients and complete notes were available for 123 patients for analyses. For all the patients managed with wire stabilisation 23% developed complications, including 13% with significant complications including nerve injuries and fracture displacements. All five nerve injuries had crossed wires, whereas all for fracture displacements had lateral wires. Baumann´s angle was 76.7 degrees in the group with no complication and 72.2 degrees in the significant complication group (p=0.02). Radiocapitellar line and anterior humeral line were not satisfactory in 5% and 15% of the group with no complications, and 17% and 33% of the group with significant complications. CONCLUSION: We found more complications in lateral pinning configurations, although all nerve injuries were in patients with crossed wire configurations. The factors we believe are associated with a higher likelihood of complications are inadequate post-operative radiological appearance.

Genomic and Gene-Expression Comparisons among Phage-Resistant Type-IV Pilus Mutants of Pseudomonas syringae pathovar phaseolicola.

Pseudomonas syringae pv. phaseolicola (Pph) is a significant bacterial pathogen of agricultural crops, and phage Φ6 and other members of the dsRNA virus family Cystoviridae undergo lytic (virulent) infection of Pph, using the type IV pilus as the initial site of cellular attachment. Despite the popularity of Pph/phage Φ6 as a model system in evolutionary biology, Pph resistance to phage Φ6 remains poorly characterized. To investigate differences between phage Φ6 resistant Pph strains, we examined genomic and gene expression variation among three bacterial genotypes that differ in the number of type IV pili expressed per cell: ordinary (wild-type), non-piliated, and super-piliated. Genome sequencing of non-piliated and super-piliated Pph identified few mutations that separate these genotypes from wild type Pph--and none present in genes known to be directly involved in type IV pilus expression. Expression analysis revealed that 81.1% of gene ontology (GO) terms up-regulated in the non-piliated strain were down-regulated in the super-piliated strain. This differential expression is particularly prevalent in genes associated with respiration--specifically genes in the tricarboxylic acid cycle (TCA) cycle, aerobic respiration, and acetyl-CoA metabolism. The expression patterns of the TCA pathway appear to be generally up and down-regulated, in non-piliated and super-piliated Pph respectively. As pilus retraction is mediated by an ATP motor, loss of retraction ability might lead to a lower energy draw on the bacterial cell, leading to a different energy balance than wild type. The lower metabolic rate of the super-piliated strain is potentially a result of its loss of ability to retract.