Busulfan, melphalan and carfilzomib high-dose chemotherapy and autologous haematopoietic stem cell transplantation in multiple myeloma.

The standard of care for fit, newly diagnosed multiple myeloma patients includes induction therapy followed by consolidative high-dose chemotherapy with melphalan and autologous stem cell transplant (AHSCT). Intensified preparative regimens, such as busulfan and melphalan (BuMel), have shown promise to lengthen progression-free survival (PFS). We previously reported that the addition of bortezomib to BuMel improved PFS compared to melphalan alone in CIBMTR-matched controls. We now integrate the second-generation protease inhibitor, carfilzomib, before and after BuMel (BuMelCar) in a phase I/II trial with carfilzomib. Patients with NDMM, relapsed/refractory MM (RRMM) and those failing prior AHSCT were eligible. Primary end-points were safety and tolerability. Secondary end-points included minimal residual disease negativity rates, PFS and OS. The study enrolled 19 patients. 73% were high risk either due to R-ISS III status, adverse genetics or relapsed after prior AHSCT. The maximum tolerated dose (MTD) of carfilzomib was determined to be 36 mg/m2. Noted grade 3 toxicities were febrile neutropenia (79%), mucositis (21%) and diarrhoea (16%). The 2-year PFS for the whole cohort and MTD was 89% and 100% respectively. 80% of all patients and 82% of patients in the MTD cohort achieved MRD negativity. Further studies regarding this regimen are planned.

Prevalence of trauma history and symptoms in patients who have received vaginal brachytherapy as part of their endometrial cancer treatment.

OBJECTIVE: Vaginal brachytherapy (VBT) is an essential component of curative intent treatment for many patients with endometrial cancer. The prevalence of trauma history in this population is unknown and important to understand considering VBT requires patients to have an instrument vaginally inserted while in the vulnerable lithotomy position. We aim to identify patients treated with intracavitary VBT and collect survey data to assess trauma endpoints. METHODS: We retrospectively identified patients with endometrial cancer who underwent intracavitary VBT at our institution between 01/2017 and 08/2022. Patients were mailed and/or electronically mailed a survey that included demographics, psychosocial background, and validated trauma surveys to be filled out as they relate to their trauma experiences prior to VBT and again considering any trauma symptomatology related to VBT. Electronic medical record review was performed. Descriptive statistics as well as multivariate analysis were performed. RESULTS: 206 patients met inclusion criteria, 66 (32.1%) of whom returned the survey and were included for analysis. Thirty-two percent of patients self-reported a personal history of any prior mental health diagnosis. Eighty-eight percent of patients screened positive for a history of trauma exposure, 23% endorsed symptoms of PTSD related to their VBT experience, and 5% screened positive for a likely PTSD diagnosis from VBT. CONCLUSION: A majority of included patients had a history of trauma exposure prior to VBT. In a subset of patients, VBT re-induced trauma and was considered to be an independent traumatic event. This study highlights the importance of practicing trauma informed care, particularly in this patient population.

Evaluating outcomes and toxicities for a newly implemented MRI-based brachytherapy program for cervical cancer.

OBJECTIVE: We report an updated analysis of the outcomes and toxicities of MRI-based brachytherapy for locally advanced cervical cancer from a U.S. academic center. METHODS: A retrospective review was performed on patients treated with MRI-based brachytherapy for cervical cancer. EBRT was standardly 45 Gy in 25 fractions with weekly cisplatin. MRI was performed with the brachytherapy applicator in situ. Dose specification was most commonly 7 Gy for 4 fractions with optimization aim of D90 HR-CTV EQD2 of 85-95 Gyα/ß=10 Gy in 2 implants each delivering 2 fractions. RESULTS: Ninety-eight patients were included with median follow up of 24.5 months (IQR 11.9-39.8). Stage IIIA-IVB accounted for 31.6% of cases. Dosimetry results include median GTV D98 of 101.0 Gy (IQR 93.3-118.8) and HR-CTV D90 of 89 Gy (IQR 86.1-90.6). Median D2cc bladder, rectum, sigmoid, and bowel doses were 82.1 Gy (IQR 75.9-88.0), 65.9 Gy (IQR 59.6-71.2), 65.1 Gy (IQR 57.7-69.6), and 55 Gy (IQR 48.9-60.9). Chronic grade 3+ toxicities were seen in the bladder (8.2%), rectosigmoid (4.1%), and vagina (1.0%). Three-year LC, PFS, and OS were estimated to be 84%, 61.7%, and 76.1%, respectively. CONCLUSION: MRI-based brachytherapy demonstrates excellent local control and acceptable rates of high-grade morbidity. These results are possible in our population with relatively large volume primary tumors and extensive local disease.

Short and long-term follow-up and clinical outcomes in patients with celiac disease in a large private practice setting.

BACKGROUND: Celiac disease (CD) is caused by an immune response to gluten and treatment is adherence to a gluten-free diet. Guidelines from studies in large academic settings recommend registered dietitian (RD) referrals at time of diagnosis and periodic testing for micronutrient deficiencies. There is limited data to guide follow-up parameters in a large, community-based practice. The purpose of this study was to evaluate guideline adherence in this setting. METHODS: This retrospective study conducted in 2019 assessed CD care based on follow-up rates, micronutrient testing, symptoms, and serology results in cohorts with and without RD referrals. Patients in this study were followed at Rockford Gastroenterology Associates (RGA): a large, private GI practice. Patients were included if they had a diagnosis of CD from 1/2014 through 12/2018, based on positive serology and/or duodenal biopsy. Patient data was collected by chart review and analyzed through Microsoft Excel. Fisher's exact and Chi-square tests were used for the statistical analysis and were calculated through the Statistical Product and Service Solutions (SPSS) software. RESULTS: 320 patients were initially reviewed and a cohort of 126 patients met inclusion criteria. 69.8% had a RD referral. 65.9% had at least one lab test order for any of the 6 micronutrients. Of 63 patients tested for iron, 11 were iron deficient (8 with RD referral). Of 64 patients tested for vitamin D, 21 were deficient (17 with referral). 80.2% attended at least one follow-up appointment, but 34.9% had only one follow-up visit over a mean follow up duration of 5.82 months. 79 patients had follow-up data for symptoms or serology and were separated into 4 categories (with vs. without RD referral): (1) asymptomatic and negative serology (32% vs. 26%), (2) symptomatic and negative serology (28% vs. 16%), (3) asymptomatic and positive serology (27% vs. 32%), (4) symptomatic and positive serology (13% vs. 26%). Category 1 yielded a fisher exact test value of 2.62 (p = 0.466). CONCLUSIONS: RD referral, micronutrient testing, and close follow-up are important parameters that affect outcomes in patients with CD. Rates for dietitian referral, some micronutrient testing and follow-up visits were higher than 50%, though results from this study were not statistically significant. Further standardization of follow-up testing and monitoring for CD will help minimize discrepancies between community-based and large, academic GI practices.

Frontal Plane Rotation of the First Ray in Hallux Valgus using Standing Computerized Tomography (CT).

The purpose of the present study was to analyze the difference in frontal plane rotation of the entire first ray in patients with and without hallux valgus using standing weightbearing computed tomography (CT). Ten feet of 10 patients with hallux valgus and 36 feet of 36 patients without hallux valgus were examined. Standing weightbearing CT scans and radiographs were taken for all subjects. Frontal plane measurements of the sesamoid apparatus, first metatarsal head, first metatarsal base, and medial cuneiform were performed. Frontal plane rotation of the first tarsometatarsal joint and intrinsic first metatarsal torsion was calculated. An independent 2 sample t test was used to compare means of outcomes of interest across control and treatment groups. Statistical significance was set at an alpha level of 0.05. There was a significant increase in pronation of the sesamoid apparatus (23.49° vs 6.60°) and first metatarsal head (17.79° vs 9.81°) in patients with hallux valgus. There was a significant increase in first metatarsal torsion toward pronation in patients with hallux valgus (22.28° vs 13.52°). No significant difference was detected in the rotation at the first tarsometatarsal joint or the frontal plane orientations of the first metatarsal base and medial cuneiform. By examining the frontal plane position of the entire first ray during weightbearing using standing CT in patients with and without hallux valgus, we determined the level at which pronation originates to be within the first metatarsal bone rather than the first tarsometatarsal joint.

Clinical and Visual Outcomes of Four Presbyopia Correcting Intraocular Lenses.

Purpose: To compare objective and subjective outcomes of the multifocal intraocular lenses ReSTOR SN6AD1 and Tecnis ZKB00, extended depth of focus IOL Symfony ZXR00, and trifocal IOL PanOptix TFNT00. Methods: This study included 262 patients (524 eyes) who had phacoemulsification with IOL implantation, 128 eyes with SN6AD1, 124 eyes with ZKB00, 136 eyes with ZXR00, and 136 eyes with TFNT00. Objective outcomes included one-month postoperative uncorrected (U) and corrected (C) distance (D) and near (N) visual acuities (VA). Subjective outcomes included photic phenomena, spectacle use, and spectacle-independent visual function. Results: Spectacle use (%) in the SN6AD1, ZKB00 ZXR00, and TFNT00 groups was 39, 64, 87, and 37 respectively (P < 0.0001). Presence of photic phenomena (%) for SN6AD1, ZKB00, ZXR00, and TFNT00 was 66, 61, and 67, and 73, respectively (P = 0.57). Spectacle-independent mean VF-14 score (%) for SN6AD1, ZKB00, ZXR00, and TFNT00 was 89.5, 87.2, 80.9, and 83.6, respectively (P < 0.01). Conclusion: All four IOLs provided excellent postoperative visual acuity and equally high rates of photic phenomena. SN6AD1 and TFNT00 provided the least spectacle use while ZXR00 had the highest spectacle use.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC. Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated. Results: Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort. Conclusion: IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

Randomized Controlled Trial of Intraocular Lens Orientation for Dysphotopsia.

PURPOSE: To evaluate whether orientation of the optic-haptic junction of an intraocular lens (IOL) during cataract surgery could decrease the incidence and/or severity of positive and negative dysphotopsia. DESIGN: Prospective, randomized controlled trial. METHODS: A total of 163 patients (326 eyes) in a private practice scheduled to have bilateral implantation of a Tecnis monofocal IOL (ZCB00) (Johnson & Johnson Vision) were randomly assigned to have the optic-haptic junction positioned vertically, horizontally, superonasally, or inferonasally. Patients with known visual field defects or best-corrected vision less than 20/80 were excluded. Patients were surveyed for positive and negative dysphotopsia symptoms at 1 week and 4-6 weeks after surgery. Patients were blinded to the orientation whereas researchers were not. Data were analyzed to compare the differences in positive and negative dysphotopsia incidence and severity. RESULTS: IOL oriented vertically in 82 eyes (25.2%), horizontally in 72 eyes (22.1%), superonasally in 94 eyes (28.8%), and inferonasally in 78 eyes (23.9%). Significant differences were noted between orientations in incidence of negative dysphotopsia at 1 week postoperatively (P = .019) and 4-6 weeks postoperatively (P = .002). Patients in the superonasal group had the worst outcome at both time periods, and the horizontal group had the best outcome at 4-6 weeks. No differences were noted for positive dysphotopsia incidence or severity. CONCLUSIONS: The orientation of the optic-haptic junction of a monofocal IOL was significantly associated with incidence of negative dysphotopsia after surgery, with the horizontal orientation performing best at 4-6 weeks.

21st Century Good Neighbor Program: An Easily Generalizable Program to Reduce Social Isolation in Older Adults.

Aim: In this once-in-a-lifetime humanitarian crisis, what does it mean to be a good neighbor? It means that as a community, we must address loneliness and barriers to care faced by vulnerable populations such as older adults. We share an inexpensive longitudinal experiential service-learning program implemented by health professions and undergraduate student volunteers that aims to help alleviate loneliness in older adults while imparting meaningful experiences to volunteers. Intervention Design and Setting: The 21st Century Good Neighbor Program is an observational cohort study of an experiential service-learning program started in May 2020, and this article shares the results collected after 1 year. This longitudinal, weekly phone call program was conducted in a single community setting in the Midwestern part of the United States. Older adults over the age of 60 served by a local community service agency (CSA) were invited to participate. Volunteers consisted of students 18 or older. Student volunteers made regular phone calls to a pair of older adults throughout the course of 1 year following standardized call scripts. The loneliness of the older adults was measured by volunteers using the 3-item UCLA Loneliness Assessment. Results: 261 older adults were engaged in conversations with a volunteer. A total of 1,391 calls were accepted by older adults and the median length of a welcomed call was 11 min. The average baseline loneliness score was 4.156 ± 1.41 and the prevalence of social isolation was 19.5%. There was no significant change in the UCLA loneliness score in the first year of follow up. However, a majority of volunteers (88%) agreed or strongly agreed that the program had a positive impact on them. In addition, the program identified 257 issues older adults faced that required follow-up. The most prevalent concerns referred to the community service agency by volunteers were issues related to utilities, food and transportation access. Conclusion: The 21st Century Good Neighbor Program is a unique intervention in which student volunteers and older adults paired by a community service agency forge relationships though a longitudinal phone call-based program. This easy-to-implement program provides another layer of support to identify and refer issues that impact social determinants of health. The added benefit of volunteer satisfaction in the setting of COVID 19 pandemic is heartening. We hope to continue to study the impact of this intervention on social isolation in this vulnerable population.

Decreased Length of Postoperative Drain Use, Parenteral Opioids, Length of Stay, and Complication Rates in Patients Receiving Meshed versus Unmeshed Acellular Dermal Matrix in 194 Submuscular Tissue Expander-Based Breast Reconstructions: A Single-Surgeon Cohort Study.

BACKGROUND: Studies have cited possible complications and increased fluid accumulation in implant-based breast reconstruction using acellular dermal matrix. The authors propose a novel approach, manually meshing acellular dermal matrix using a skin graft mesher before use in expander-based breast reconstruction. The authors investigated postoperative drain time, complication rates, pain, and length of hospital stay in meshed versus unmeshed acellular dermal matrix cohorts. METHODS: One hundred fourteen patients and 194 reconstructed breasts were included overall. Of these, 99 patients were included in the pain and postoperative length of hospital stay analysis. Independent t test and chi-square analyses were used for bivariate comparisons. Multiple linear regression analyses were used to further delineate impact of meshing acellular dermal matrix on drain time, postoperative parenteral narcotic requirements, and length of stay between the two cohorts. RESULTS: The meshed acellular dermal matrix cohort had lower overall complication rates compared with the unmeshed cohort. Multiple linear regression analyses showed meshing the acellular dermal matrix alone decreased drain time by 7.3 days, and decreased postoperative parenteral narcotic requirements by 77 percent (20 mg morphine). Furthermore, it was the only significant predictor for a decrease in length of stay. CONCLUSIONS: Meshing acellular dermal matrix significantly decreased the time needed for postoperative drains. Statistical analysis showed significantly decreased overall and minor complication rates in the meshed cohort. Meshing significantly decreased parenteral narcotic requirements and, importantly, also decreased length of stay. All of these factors have important implications regarding cost and quality of care in expander-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Improved Nutrition Status in Patients With Advanced Heart Failure Implanted With a Left Ventricular Assist Device.

BACKGROUND: Left ventricular assist device (LVAD) implantation for advanced heart failure is known to improve survival, functional capacity, and quality of life. Most patients implanted with LVADs suffer from moderate to severe malnutrition and deconditioning due to their advanced disease. The Mini Nutritional Assessment (MNA) and the short form of the survey (MNA-SF) are 2 well-validated clinical tools, previously used to assess patient nutrition status in numerous conditions. Earlier work has demonstrated that low nutrition scores can independently predict mortality in the LVAD population. This study explored changes in MNA scores and other clinical markers following LVAD. METHODS: This retrospective study included 74 patients implanted with LVADs between 2012 and 2017. MNA or MNA-SF along with other clinical data and nutrition indices were assessed during the preoperative workup and reassessed on average 423.9 days post LVAD. Paired-samples t-tests were used to evaluate any changes. RESULTS: Despite an average body mass index of 30.8, 28.3% of patients were classified by MNA as malnourished, and 58.5% were considered at risk prior to LVAD implantation. Post LVAD implantation, MNA scores improved from an average of 19.2-23.0 (P < 0.001), with now only 3.8% classified as malnourished and 45.3% classified as at risk. MNA-SF and prognostic nutritional index also improved significantly. CONCLUSIONS: This study indicates that LVAD implantation is associated with a long-term improvement in nutrition status when compared with the preoperative heart failure state.

Use of a patient empowerment tool for hand hygiene.

BACKGROUND: Patient empowerment is recognized as an important component of a multimodal strategy to improve hand hygiene adherence. We examined the attitudes of adult patients and parents of pediatric patients toward a new patient empowerment tool (PET) at our hospital. We also surveyed physicians to determine their perceptions about the PET. METHODS: A cross-sectional survey was performed of hospitalized children's parents and adult patients in a 531-bed tertiary care teaching hospital in West Virginia. Surveys were anonymous and self-administered. A separate survey was administered via e-mail to resident and attending physicians from the departments of internal medicine, pediatrics, and family medicine. RESULTS: Most parents and adult patients felt it was their role to speak up if a provider did not perform hand hygiene, but a smaller number actually felt comfortable using the PET. Only 54.9% of physicians felt that patients should be involved in reminding providers to perform hand hygiene. Overall, physicians indicated that they would prefer a patient to use words rather than the PET to remind them to perform hand hygiene. CONCLUSIONS: In our study, parents and adult patients supported use of the PET, but physicians were less supportive. As the patient empowerment movement grows, we should work to improve physician acceptance of patient involvement if it is to be successful.