Surgical management of pain or infection secondary to calciphylaxis: a wound center's experience and algorithmic multidisciplinary approach.

BACKGROUND: The role of surgical management of calciphylaxis remains understudied. OBJECTIVE: This article reports a case series and algorithmic approach to the multidisciplinary management of calciphylaxis. METHODS: A single-center retrospective review of all adult patients with calciphylaxis treated surgically between January 2010 and November 2022 was performed. RESULTS: Eleven patients met inclusion criteria. The average age was 50.9 years ± 15.8 SD, and most patients were female (n = 7 [63.6%]). Surgery was indicated for infection (n = 6 [54.5%]) and/or intractable pain (n = 11 [100%]). Patients underwent an average of 2.9 excisional debridements during their hospital course. Following the final excision, wounds were left open in 5 cases (29.4%), closed primarily in 4 (23.5%), and local flaps were used in 3 (27.3%). Postoperatively, the mean time to healing was 57.4 days ± 12.6. Complications included dehiscence (n = 1 [9.1%]), progression to cellulitis (n = 2 [18.2%]), osteomyelitis (n = 1 [9.1%]), and lower extremity amputation (n = 2 [18.2%]). Of the 6 patients alive at the time of healing, 5 (83.3%) were no longer taking narcotic medications. At an average follow-up of 26.4 months ± 34.1, 7 patients (63.6%) were deceased, with an average time to mortality of 4.8 months ± 6.7. Of the 4 remaining patients, 3 (75.0%) were ambulatory by their most recent follow-up visit. CONCLUSION: While the morbidity and mortality associated with calciphylaxis are substantial, surgical excision is effective in reducing pain and improving quality of life in patients with this end-stage disease. Wound care centers are uniquely equipped with a variety of medical and surgical specialists with experience in treating chronic wounds and thus facilitate an efficient multidisciplinary model.

COVID-19 Vaccination Status and Capsular Contracture Following Prosthetic Breast Reconstruction: A Retrospective, Multicenter Nested Case-Control Study.

BACKGROUND: Capsular contracture (CC) is a common long-term complication following prosthetic-based breast reconstruction (PBBR). Seven cases of CC following mRNA vaccination for coronavirus 2019 (COVID-19) are reported in the literature. OBJECTIVES: The aim of this study was to determine whether receiving the COVID-19 vaccine was associated with CC development following PBBR. METHODS: A retrospective, multicenter nested case-control study was performed from January 2014 to July 2022 of adult female patients who underwent PBBR with acellular dermal matrix placement. Cases of CC were selected if no adjuvant radiation was received and they presented for follow-up between December 2020 and July 2022. Controls included patients who met inclusion criteria but who did not experience CC in either breast. Patient demographics, breast cancer characteristics, reconstructive surgery details, postoperative complications, and COVID-19 exposure details were analyzed and correlated with CC development. RESULTS: Of a total of 230 patients (393 breasts) who received PBBR, 85 patients (135 breasts) met inclusion criteria, of whom 12 patients (19 breasts) developed CC and 73 patients (116 breasts) did not. At the time of median follow-up of 18.1 months (n = 85; interquartile range, 12.2-33.6 months), no statistically significant differences were observed between the short- or long-term complications in cases or controls. There were no significant differences in COVID-19 vaccination status, number of vaccine doses, or vaccination type between cases and controls. Vaccination status was not associated with greater odds of CC development (odds ratio, 1.44; 95% CI, 0.42-5.37; P > .05). CONCLUSIONS: Direct association between CC and COVID-19 vaccination is difficult to prove. Given the known risk of severe COVID-19 infection among immunocompromised patients, those with breast cancer who undergo PBBR should be properly counseled on the benefits and risks of vaccination.

Cryopreservation of buffy coat derived platelets: Paired in vitro characterization using uncontrolled versus controlled freezing rate protocols.

BACKGROUND: Cryopreserved platelets show a reduced recovery and viability after freezing and thawing including several ultrastructural and phenotypic deteriorations compared with liquid-stored platelets. It is suggested that using Controlled-Rate Freezing (CRF) can reduce variability and optimize the functionality profile for cells. The objective of the study is to compare cellular, metabolic, phenotypic and functional effects on platelets after cryopreservation using different freezing rate protocols. STUDY DESIGN AND METHODS: To evaluate the possible effects of different freezing rate protocols a two-experimental study comparing diverse combinations was tested with a pool and split design. Uncontrolled freezing of platelets in materials with different thermal conductivity (metal vs cardboard) was evaluated in experiment 1. Experiment 2 evaluated uncontrolled vs a controlled-rate freezing protocol in metal boxes. All variables were assessed pre and post cryopreservation. RESULTS: Directly after thawing, no major differences in platelet recovery, LDH, ATP, Δψ, CD62P, CD42b, platelet endothelial cell adhesion molecule and sCD40L were seen between units frozen with different thermal conductivity for temperature. In contrast, we observed signs of increased activation after freezing using the CRF protocol, reflected by increased cell surface expression of CD62P, PAC-1 binding and increased concentration of LDH. Agonist induced expression of a conformational epitope on the GPIIb/IIIa complex and contribution to blood coagulation in an experimental rotational thromboelastometry setup were not statistically different between the groups. CONCLUSION: The use of a uncontrolled freezing rate protocol is feasible, creating a platelet product comparable to using a controlled rate freezing equipment during cryopreservation of platelets.

Development and Optimization of Chromosomally-Integrated Fluorescent Mycobacterium tuberculosis Reporter Constructs.

Mycobacterium tuberculosis resides in the lungs in various lesion types with unique microenvironmental conditions. This diversity is in line with heterogeneous disease progression and divergent drug efficiency. Fluorescent reporter strains can be used to decipher the micromilieu and to guide future treatment regimens. Current reporters using replicating plasmids, however, are not suitable for long-term mouse infections or studies in non-human primates. Using a combination of recombinant DNA and protein optimization techniques, we have developed reporter strains based on integrative plasmids, which exhibit stimulus-response characteristics and fluorescence intensities comparable to those based on replicating plasmids. We successfully applied the concepts by constructing a multi-color reporter strain able to detect simultaneous changes in environmental pH, Mg2+ concentrations, and protein expression levels.

Amount of naloxone used to reverse opioid overdoses outside of medical practice in a city with increasing illicitly manufactured fentanyl in illicit drug supply.

Background: Illicitly manufactured fentanyl (IMF) prevalence has increased. However, there is uncertainty about naloxone dose(s) used by nonmedical bystanders to reverse opioid overdoses in the context of increasing IMF. Methods: We used community naloxone distribution program data about naloxone doses and fatal opioid overdoses from the Allegheny County Medical Examiner. From January 2013 to December 2016, staff interviewed participants who administered naloxone in response to 1072 overdoses. We calculated frequencies, percentages, and conducted a 1-way analysis of variance (ANOVA). Results: Despite increases in fentanyl-contributed deaths, there were no statistically significant differences between any of the 4 years (2013-2016) on average number of naloxone doses used by participants to reverse an overdose (F = 0.88; P = .449). Conclusion: Even though IMF is more potent than heroin and is a rapidly increasing contributor to drug overdose deaths in Allegheny County, the average dose of naloxone administered has not changed. Our findings differ from studies in different areas also experiencing increasing IMF prevalence. Additional investigations are needed to clarify the amount of naloxone needed to reverse opioid overdoses in the community caused by new synthetic opioids.

From Peers to Lay Bystanders: Findings from a Decade of Naloxone Distribution in Pittsburgh, PA.

Distribution of the opioid overdose reversal drug naloxone has been central to efforts to combat the ongoing opioid epidemic in the United States. This report presents data from Prevention Point Pittsburgh (PPP), a public health advocacy and direct service organization that has operated an overdose prevention program (OPP) with naloxone distribution since 2005. The program initially provided naloxone training and distribution only to people who use opioids (PWUO). In 2015, a change to state law enabled PPP to provide naloxone to anyone in a position to respond to an opioid-related overdose. This report examines the characteristics and naloxone-related experiences of 1330 PWUO trained in overdose prevention and naloxone administration by PPP between January 1, 2006, and December 31, 2015, and compares rates of return for a naloxone refill by PWUO and the 619 non-users trained between January 1, 2015, and December 31, 2015. While larger numbers of individuals obtained naloxone after state law changed, PWUO-especially heroin users-were significantly more likely to reverse an overdose and return to PPP for a naloxone refill. Based on these findings, we recommend that resource-limited, community-based organizations prioritize the distribution of naloxone to PWUO.

Cost effectiveness of enhanced recovery after surgery programme for vaginal hysterectomy: a comparison of pre and post-implementation expenditures.

Enhanced Recovery After Surgery programmes were first conceived to optimise perioperative patient care and have been delivered by surgical specialities in the UK for over a decade. Although their safety and acceptability have been ratified in many surgical fields including gynaecology and colorectal surgery, the cost effectiveness of its implementation in benign vaginal surgery remains unclear. In this case-control study, the perioperative expenditure for 45 women undergoing vaginal hysterectomy at a North London teaching hospital after implementation of an enhanced recovery pathway was compared with 45 matched controls prior to implementation. Frequency of catheter use (84.4% vs. 95.6%) and median length of stay (23.5 vs. 42.9 h) were significantly lower following implementation of pathway (both p < 0.05). Although enhanced recovery patients were more likely to attend the accident and emergency department for minor symptoms following discharge (15.6% vs. 0%, p < 0.05), the inpatient readmission rate (6.7% vs. 0.0%, p > 0.05) was similar in both groups. Establishing the programme incurred additional expenditures including delivering a patient-orientated gynaecology 'school' and employing a specialist enhanced recovery nurse, but despite these, we demonstrated a saving of 15.2% (or £164.86) per patient. The cost efficiency savings, coupled with increased satisfaction and no rise in morbidity, offers a very attractive means of managing women undergoing vaginal hysterectomy. We believe that our data can be reproduced in other centres and recommend that the pathway be used routinely in women undergoing these procedures.

Can enhanced recovery pathways improve outcomes of vaginal hysterectomy? Cohort control study.

STUDY OBJECTIVE: To assess the effect of enhanced recovery pathway implementation on patient outcomes after vaginal hysterectomy (VH) performed to treat benign indications. DESIGN: Case-control study examining outcome measures including length of stay, pain scores, postoperative morbidity, and readmission rates after implementation of the Enhanced Recovery after Surgery (ERAS) program for VH (Canadian Task Force classification II). SETTING: Teaching hospital. PATIENTS: Fifty patients who underwent VH after implementation of ERAS were compared with 50 control patients before ERAS. Patients were matched for age, indication for surgery, American Society of Anesthesiologists grade, and surgeon. INTERVENTION: ERAS pathway. MEASUREMENTS AND MAIN RESULTS: Length of stay, percentage of patients discharged within 24 hours, use of urinary catheter and vaginal packing, and readmission rates were determined. Perioperative expenditures were compared, and cost-effectiveness of ERAS was assessed. Median patient vs control age (49.0 vs 51.0 years), parity (2.0 vs 2.0), and body mass index (26.5 vs 28.3) were statistically comparable. After ERAS implementation, the median length of stay was reduced by 51.6% (22.0 vs 45.5 hours; p < .01), and the percentage of patients discharged within 24 hours was increased by 5-fold (78.0 vs 15.6%; p < .05). Frequency of catheter use (82.0% vs 95.6%) and use of vaginal packing (52.0 vs 82.2%) were significantly lower in the post-ERAS group, and these devices were removed earlier (14.5 vs 23.7 hours and 16.0 vs 23.0 hours, respectively; p < .05 in all cases). Attendance in the Accident and Emergency Department (12.0% vs 0%; p > .05) and inpatient readmission rate (4.0% vs 0%; p > .05) were similar in both groups. Despite having to start a "gynecology school" and employ a specialist Enhanced Recovery nurse, a cost savings of 9.25% per patient was demonstrated. CONCLUSION: The ERAS program in benign VH reduces length of stay by 51.6% and enables more women to be discharged within 24 hours, with no increase in patient readmissions rates.

Characteristics of an overdose prevention, response, and naloxone distribution program in Pittsburgh and Allegheny County, Pennsylvania.

Prevention Point Pittsburgh (PPP) is a public health advocacy organization that operates Allegheny County's only needle exchange program. In 2002, PPP implemented an Overdose Prevention Program (OPP) in response to an increase in heroin-related and opioid-related overdose fatalities in the region. In 2005, the OPP augmented overdose prevention and response trainings to include naloxone training and prescription. The objective of our study is to describe the experiences of 426 individuals who participated in the OPP between July 1, 2005, and December 31, 2008. Of these, 89 individuals reported administering naloxone in response to an overdose in a total of 249 separate overdose episodes. Of these 249 overdose episodes in which naloxone was administered, participants reported 96% were reversed. The data support findings from a growing body of research on similar programs in other cities. Community-based OPPs that equip drug users with skills to identify and respond to an overdose and prescribe naloxone can help users and their peers prevent and reverse potentially fatal overdoses without significant adverse consequences.