Comparing Transcervical Balloon with Osmotic Dilators for Cervical Preparation Prior to Procedural Abortion: a Non-Inferiority Randomized Trial.

OBJECTIVE: To compare cervical preparation with transcervical balloon to osmotic dilators for second-trimester procedural abortions. STUDY DESIGN: We performed an unblinded, randomized, non-inferiority trial of people undergoing second-trimester procedural abortion at 18+0 to 23+6 weeks gestation. We randomized participants to either overnight osmotic dilators (Dilapan-S) or transcervical balloon (Foley). Both groups received overnight mifepristone and pre-procedural misoprostol. We powered the study on mean difference in procedure duration; non-inferiority limit 5 minutes. We compared pre-procedure cervical dilation; need for additional dilation; and, using 100-point visual analogue scale, measured physician satisfaction and ease of procedure, and participant pain and satisfaction. RESULTS: We recruited 32 participants at a single academic center. Although procedure time (minutes) was similar (balloon: 22.6+8.9 vs Dilapan-S: 22.4+12.8, p=0.96), non-inferiority was not met (mean difference, 0.2 minutes; 95% confidence interval, -7.8 to 8.2). Cervical dilation >2cm was more likely after Dilapan-S (100% vs 62.5%, p=0.02). Placement was well tolerated with similar time (minutes) for insertion (balloon: 4.8+1.0, Dilapan-S: 5.1+2.3, p=0.64) and maximum pain (median) with insertion (balloon 39 (5-78), Dilapan-S: 39 (0-100), p=0.92). Pain immediately post-insertion was higher for Dilapan-S (33 (0-100) vs 18 (0-50), p=0.046), and similar for maximum pain overnight, participant satisfaction, and likelihood to recommend. Complications were minor and similar between groups (p=0.60). CONCLUSION: While significantly more people with transcervical balloon required mechanical dilation, the difference in operative time was clinically negligible. The transcervical balloon was well tolerated and acceptable by participants. IMPLICATIONS: Clinicians experienced in mechanical dilation may consider a transcervical balloon as a lower-cost tool for second-trimester abortion cervical preparation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT05099991.

Relationship between 25-hydroxy Vitamin D level and surgical site infection in spine surgery.

Background: 25-hydroxy Vitamin D (25[OH]D) level has been shown to have antimicrobial and wound healing effects in animal models. Low preoperative 25(OH)D has been shown to correlate with surgical site infection (SSI) in thoracolumbar spine surgery. Methods: This study involved 545 patients undergoing thoracolumbar spine surgery from 2012 to 2019 at an academic medical center. We evaluated the serum 25(OH)D level (i.e., adequate level = level 30-60 ng/dL), along with SSI, body mass index, and smoking status. Statistical analysis was done using bivariate analysis with Fisher's exact, Wilcoxon rank-sum test and multivarible logisitic regression analyses. Results: We included 545 patients in the study, and there were no statistical differences in the average preoperative 25(OH)D between SSI and non-SSI groups. The average 25(OH)D in the non-SSI group was 31.6 ng/dL ± 13.6, and the SSI group was 35.7 ng/dL ± 20.2 (P = 0.63). Conclusion: SSI rates following thoracolumbar spine surgery were not affected by preoperative 25(OH)D levels.

Cervical preparation for second-trimester procedural abortion.

PURPOSE OF REVIEW: To review the evidence-informed options for cervical preparation prior to second-trimester dilation and evacuation (D&E). RECENT FINDINGS: As abortion restrictions increase and the number of abortion clinics and providers decreases, pregnant people are facing more barriers to abortion access. Those in need are now often required to travel for second-trimester abortion care, only to be faced with additional restrictions, such as mandatory waiting periods. Cervical preparation is recommended prior to D&E and takes time for effect. Given the increasing time required to obtain an abortion, patients and providers may prefer same-day cervical preparation to decrease the total time required. Options for same-day cervical preparation include misoprostol alone with single or serial doses, and misoprostol combined with osmotic dilators or transcervical balloon (Foley catheter). Same-day preparation may require additional clinical space to accommodate people after initiation of cervical preparation to manage side-effects and timing of the abortion. Overnight options are also used and more frequently later in the second trimester. Overnight options include mifepristone, osmotic dilators, and transcervical balloon and are often combined with same-day misoprostol. Medication alone preparation is well tolerated and effective in the second trimester, with the addition of mechanical methods with advancing gestation. With many options and combinations being safe and effective, providers can be dynamic and alter approach with supply shortages, adjust to different clinical settings, consider patient medical and surgical factors, and accommodate provider and patient preferences. SUMMARY: Multiple pharmacologic and mechanical options have been shown to be safe and effective for cervical preparation prior to D&E. Consideration for multiple factors should influence the method of cervical preparation and methods may vary by patient, provider and setting.

Perioperative Complications and Radiographic Outcomes Following Cervical Laminoplasty: A Review of 105 Cases from a Single Academic Center.

OBJECTIVE: To assess complications and to compare preoperative and postoperative radiographic measures in patients who underwent cervical laminoplasty. METHODS: We evaluated patients undergoing cervical laminoplasty between 2011 and 2022 at an academic medical center. Patient demographics, intraoperative and postoperative complications, and preoperative and postoperative radiographic parameters were recorded. RESULTS: Of 150 patients undergoing cervical laminoplasty during 2011-2022, 105 met the inclusion criteria. We identified 22 (21.0%) adverse events in 20 patients: 4 intraoperative (3.8%), 10 perioperative (9.5%), and 8 delayed postoperative (7.6%). Among adverse events, 13 (12.4%) were judged to be minor and 9 (8.6%) were judged to be major complications. Revision surgery was required in 6 (5.7%) patients. Both preoperative and postoperative cervical spine radiographic imaging was available in 47 (44.8%) of the 105 patients. Mean preoperative and postoperative C2-7 Cobb angles were 14.7° and 12.3°, respectively (P = 0.04). Mean preoperative and postoperative sagittal vertical axis measurements were 29.2 mm and 33.3 mm, respectively (P = 0.07). Mean preoperative and postoperative T1 slopes were 32.3° and 30.2°, respectively (P = 0.07). CONCLUSIONS: Cervical laminoplasty carries a significant risk of adverse events, the majority of which are minor, and has a low rate of reoperation (5.7%). The procedure does not result in significant changes in sagittal vertical axis or T1 slope. Cervical laminoplasty remains a valuable surgical option for selected patients with cervical myelopathy.

Progestins of today and tomorrow.

PURPOSE OF REVIEW: To review the current literature on the multiple types and uses of progestins in reproductive healthcare. RECENT FINDINGS: Progestins for contraceptive use are available in multiple forms, with the ongoing development of transdermal, intravaginal, and male contraception formulations. Noncontraceptive use of progestins often overlaps with contraceptive indications, which allows for simultaneous multipurpose progestin use, especially in reproductive-aged patients. More studies are needed to determine contraceptive doses of progestins used for noncontraceptive purposes. Side effect profiles of progestins are dependent on their formulation and cross-reactivity with other steroid receptors. Development of newer progestins includes manipulating pharmacologic properties to avoid undesired side effects. SUMMARY: Progestins have multiple uses in reproductive healthcare, including contraception, menstrual suppression, endometrial protection, and hormonal replacement therapy. The development of progestins for these indications can expand therapy for people with contraindications to estrogen-based hormonal therapy.

Role of GM-CSF in regulating metabolism and mitochondrial functions critical to macrophage proliferation.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) exerts pleiotropic effects on macrophages and is required for self-renewal but the mechanisms responsible are unknown. Using mouse models with disrupted GM-CSF signaling, we show GM-CSF is critical for mitochondrial turnover, functions, and integrity. GM-CSF signaling is essential for fatty acid ß-oxidation and markedly increased tricarboxylic acid cycle activity, oxidative phosphorylation, and ATP production. GM-CSF also regulated cytosolic pathways including glycolysis, pentose phosphate pathway, and amino acid synthesis. We conclude that GM-CSF regulates macrophages in part through a critical role in maintaining mitochondria, which are necessary for cellular metabolism as well as proliferation and self-renewal.

Pain management in outpatient surgical abortion.

PURPOSE OF REVIEW: To review the current literature focusing on pain management and experiences during abortion care. RECENT FINDINGS: Analgesic options in abortion care address pain associated with the procedure, osmotic dilator insertion, and cervical preparation. The paracervical block (PCB) is effective for pain control in first and second trimester abortions. Lower volume PCBs demonstrate non inferiority with osmotic dilator placement compared with higher volume PCBs with lower potential for toxicity. Self-administered vaginal lidocaine gel is noninferior to PCB in first trimester abortions. Preoperative oral narcotics and sedation do not reduce pain in first trimester abortions; however, the latter may reduce anxiety. For second trimester abortions, narcotics or gabapentin do not improve postoperative pain, yet up to half of patients will use narcotics if offered. Nonpharmacological methods have shown success in pain management. Music and doula support do not improve pain; however, patients would recommend these modalities, indicating some benefit that went unmeasured. Auricular acupuncture and transcutaneous electrical nerve stimulation (TENS) reduce pain and anxiety during first trimester abortions. SUMMARY: Several modalities reduce pain during abortion care; however, pain alone does not reflect patient satisfaction. Development of multidimensional measures for pain control assessment has the potential to capture the patient's overall experience.

Risk Factors for Failed Nonsurgical Treatment Resulting in Surgery on Thumb Carpometacarpal Arthritis.

PURPOSE: The thumb carpometacarpal (CMC) joint is the second most common site of osteoarthritis in the hand, yet reported symptoms and ultimate treatment decisions are not simply a function of radiographic appearance. This study aimed to determine the patient- and/or disease-related factors associated with patients undergoing surgical treatment of thumb CMC arthritis. METHODS: This retrospective cohort study analyzed 1,994 patients with thumb CMC arthritis treated at 2 institutions between February 2015 and November 2018. Patient demographic and clinical information was obtained from medical records to characterize treatment modalities before hand surgeon evaluation, mental and physical comorbidities, and Patient-Reported Outcomes Measurement Information System assessments. After bivariate analysis, a multivariable logistic regression model evaluated factors associated with undergoing thumb CMC surgery. RESULTS: This cohort was predominately female (70%) and white (91%), mean age at first appointment, 62 ± 10 years. A total of 170 patients underwent surgery for thumb CMC arthritis (9%) at a median of 114 days (interquartile range, 27-328) after the first visit. Patient-Reported Outcomes Measurement Information System Depression scores correlated with Pain Interference and Physical Function scores. A history of diagnosed depression or anxiety was associated with less perceived Physical Function at presentation. However, only prior contralateral thumb CMC surgery, younger patient age, and treating institution were associated with undergoing surgery in regression modeling. CONCLUSIONS: Pain and functional limitations associated with thumb CMC arthritis are influenced by mental health comorbidities, but these factors do not predict surgical treatment. Instead, patients' prior surgical experience and surgeon attitudes toward thumb CMC arthritis appear to have a strong influence on the odds of patients undergoing surgery for thumb CMC arthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

A single-blinded randomized controlled trial evaluating pain and opioid use after dilator placement for second-trimester abortion.

OBJECTIVES: To compare pain levels and medication needs after placement of laminaria vs Dilapan-S, and after dilation and evacuation (D&E). STUDY DESIGN: We conducted a single-blinded randomized control trial of patients undergoing D&E at 15 0/7 to 23 6/7 weeks gestation, randomizing to cervical preparation with laminaria or Dilapan-S. We compared pain levels and medication usage following dilator placement (5 minutes; 2, 4, and 8 hours; the following morning) and D&E (1, 4, 24, and 48 hours). Our primary outcome was median change from baseline pain, and secondary outcomes included maximum pain timing and overall narcotic use. We compared baseline characteristics, median pain increases and quantities of narcotics used. RESULTS: We analyzed 67 participants with laminaria (n = 34) and Dilapan-S (n = 33). More Dilapan-S users had a prior vaginal delivery (n = 20, 60.6%) than laminaria users (n = 11, 32.4%), p = 0.02. Maximum median pain was not statistically different (Laminaria: +3.5 (interquartile range [IQR] +0.5, +6.5); Dilapan-S: +3 (IQR +1, +5); p = 0.42. Thirty-seven (63.8%) participants reported higher levels of pain following dilator placement than D&E. Overall, 26 (42.6%) participants used narcotics during their abortion episode, with no difference in median number of tablets between laminaria (2, range 1-8) and Dilapan-S (4.5, range 1-15) participants (p = 0.34). CONCLUSIONS: Median pain increase did not differ in participants receiving laminaria or Dilapan-S for cervical preparation prior to D&E. The majority of patients will use a small amount of narcotics if available. IMPLICATIONS: The lack of difference in pain between laminaria and Dilapan-S enhances the applicability of pain intervention research across dilator types. With over half of participants using a small amount of narcotics during their D&E episode, pain management should be individualized to patient needs.

Trajectory analysis quantifies transcriptional plasticity during macrophage polarization.

In recent years, macrophages have been shown to be tremendously plastic in both in vitro and in vivo settings; however, it remains unclear whether macrophages retain any persistent memory of past polarization states which may then impact their future repolarization to new states. Here, we perform deep transcriptomic profiling at high temporal resolution as macrophages are polarized with cytokines that drive them into "M1" and "M2" molecular states. We find through trajectory analysis of their global transcriptomic profiles that macrophages which are first polarized to M1 or M2 and then subsequently repolarized demonstrate little to no memory of their polarization history. We observe complete repolarization both from M1 to M2 and vice versa, and we find that macrophage transcriptional phenotypes are defined by the current cell microenvironment, rather than an amalgamation of past and present states.

Etonogestrel concentrations among contraceptive implant users in Botswana using and not using dolutegravir-based antiretroviral therapy.

OBJECTIVES: To evaluate whether etonogestrel concentrations are reduced to a level that could potentially reduce contraceptive efficacy when the etonogestrel contraceptive implant is used concomitantly with dolutegravir-based antiretroviral therapy (ART). STUDY DESIGN: We conducted a non-randomized, open-label, cross-sectional pharmacokinetic study among women using single-rod etonogestrel contraceptive implants in Botswana. We compared plasma etonogestrel concentrations, sampled at a single time-point between 3 and 12 months from implant insertion, among implant users living with HIV and receiving dolutegravir-based ART with HIV-negative implant users. We also assessed concentrations among implant users living with HIV and receiving efavirenz-based ART. We compared geometric mean etonogestrel concentrations analyzing data from 142 participants: 97 HIV-negative, 30 using dolutegravir, and 15 using efavirenz. RESULTS: The groups were similar. Duration of implant use was between 3 and 12 months (median = 5). Geometric mean etonogestrel plasma concentrations and 90% confidence intervals of the mean were 227.5(212.4-243.8), 289.6(251.8-333.0) and 76.4(63.9-91.4) pg/mL among the HIV-negative, dolutegravir- and efavirenz-based ART groups, respectively. All women in the HIV-negative and dolutegravir-based ART groups had etonogestrel concentrations above 90 pg/mL; 9/15 women (60%) using efavirenz-based ART had concentrations below 90 pg/mL. On average, etonogestrel levels were lower among individuals who had implants inserted for longer durations. CONCLUSIONS: Implant users receiving dolutegravir-based ART had a higher mean etonogestrel concentration compared to HIV-negative women, and none had etonogestrel concentrations below the posited threshold for ovulation suppression. In contrast, women in the efavirenz-group had much lower etonogestrel concentrations. Overall, these data provide evidence that the etonogestrel implant may be effectively combined with dolutegravir-based ART regimens. IMPLICATIONS: The etonogestrel implant remains a highly effective contraceptive option for women living with HIV who use dolutegravir-based ART.

Ankle Motion and Offloading in Short Leg Cast and Low and High Fracture Boots.

BACKGROUND: Short leg casts (SLCs) and fracture boots are used to treat foot and ankle injuries, but the decision to use one device over the other is often subjective. This study compared the impact of SLCs and low and high fracture boots on ankle motion and offloading. METHODS: Twenty healthy adults were prospectively studied. High-speed dynamic radiography was utilized to determine tibiotalar range of motion in the sagittal plane during nonweightbearing (NWB) and weightbearing (WB) gait in a shoe (control), SLC, and low and high fracture boots. Sensors captured peak plantar surface forces to determine ankle offloading. RESULTS: In NWB, the low fracture boot (2.2 ± 2.0 degrees), high fracture boot (2.3 ± 1.6 degrees), and SLC (2.3 ± 1.5 degrees) had significantly less motion compared with the control (3.6 ± 2.1 degrees; P ≤ .026). During WB, the SLC (3.4 ± 1.4 degrees) and high fracture boot (4.8 ± 2.0 degrees) had less motion compared with the low fracture boot (7.8 ± 3.4 degrees; P < .001). Finally, the SLC (172.6% ± 48.3% body weight [BW]) and low fracture (165.1% ± 36.2% BW) and high fracture (154.5% ± 32.9% BW) boots were associated with less peak plantar surface force compared with the control (195.0% ± 43.8% BW; P ≤ .087). CONCLUSION: The SLC and high fracture boot immobilized the ankle in NWB and offloaded and immobilized the ankle in WB. The low fracture boot also immobilized the ankle in NWB, but in WB, the low fracture boot only offloaded the ankle and did not immobilize it. CLINICAL RELEVANCE: The low fracture boot may be more suited for NWB or possibly immobilizing the foot in WB.

Clinical Characteristics and Long-term Outcomes After Septic Arthritis of the Native Glenohumeral Joint: A 20-Year Retrospective Review.

Septic arthritis of the native glenohumeral joint is rare, and there is little information available regarding the natural progression and long-term joint outcomes of this pathology. The authors performed a retrospective analysis of 97 patients with culture-positive glenohumeral septic arthritis between 1995 and 2015 at their institution with a mean clinical follow-up of 83.1 months. Patient records were reviewed to document demographic and laboratory data, clinical presentation, postoperative complications, recurrences, and subsequent shoulder arthroplasty. Common comorbidities uncovered included 20 immunocompromised patients (20.6%), intravenous drug use among 27 patients (27.8%), diabetes mellitus among 40 patients (41.2%), and 18 patients (18.5%) receiving hemodialysis. Staphylococcus aureus was the most common pathogen identified (61 patients; 62.8%), followed by streptococcal species (17 patients; 17.2%). Hematogenous spread of infection was the most common etiology of shoulder sepsis (40.2%). Seven patients (7.2%) developed shoulder sepsis of undetermined etiology in the absence of established risk factors, and 16 patients (16.4%) developed recurrent glenohumeral septic arthritis at a mean of 40 months following initial eradication of infection. Three patients (3.0%) eventually underwent same-side shoulder arthroplasty at a mean of 18 months following septic arthritis, with none experiencing a periprosthetic joint infection. Glenohumeral septic arthritis is highly unlikely in the absence of medical risk factors. Long-term recurrence after clinically successful treatment is low (16.5%), and few patients undergo elective arthroplasty following shoulder septic arthritis. However, orthopedic surgeons can expect 30% to 40% of patients to require multiple trips to the operating room to successfully treat the initial joint infection, regardless of treatment method. [Orthopedics. 2019; 42(1):e118-e123.].

iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice.

Induced pluripotent stem cell (iPSC)-derived hematopoietic cells represent a highly attractive source for cell and gene therapy. Given the longevity, plasticity, and self-renewal potential of distinct macrophage subpopulations, iPSC-derived macrophages (iPSC-Mφ) appear of particular interest in this context. We here evaluated the airway residence, plasticity, and therapeutic efficacy of iPSC-Mφ in a murine model of hereditary pulmonary alveolar proteinosis (herPAP). We demonstrate that single pulmonary macrophage transplantation (PMT) of 2.5-4 × 106 iPSC-Mφ yields efficient airway residence with conversion of iPSC-Mφ to an alveolar macrophage (AMφ) phenotype characterized by a distinct surface marker and gene expression profile within 2 months. Moreover, PMT significantly improves alveolar protein deposition and other critical herPAP disease parameters. Thus, our data indicate iPSC-Mφ as a source of functional macrophages displaying substantial plasticity and therapeutic potential that upon pulmonary transplantation will integrate into the lung microenvironment, adopt an AMφ phenotype and gene expression pattern, and profoundly ameliorate pulmonary disease phenotypes.

Single-cell transcriptome sequencing: recent advances and remaining challenges.

Single-cell RNA-sequencing methods are now robust and economically practical and are becoming a powerful tool for high-throughput, high-resolution transcriptomic analysis of cell states and dynamics. Single-cell approaches circumvent the averaging artifacts associated with traditional bulk population data, yielding new insights into the cellular diversity underlying superficially homogeneous populations. Thus far, single-cell RNA-sequencing has already shown great effectiveness in unraveling complex cell populations, reconstructing developmental trajectories, and modeling transcriptional dynamics. Ongoing technical improvements to single-cell RNA-sequencing throughput and sensitivity, the development of more sophisticated analytical frameworks for single-cell data, and an increasing array of complementary single-cell assays all promise to expand the usefulness and potential applications of single-cell transcriptomic profiling.

Mesenteric vascular thrombosis associated with disseminated abdominal visceral hemangiosarcoma in a cat.

An adult castrated male cat was evaluated because of a 4 day history of lethargy and partial anorexia. Physical examination revealed abdominal pain with a palpable fluid wave. Cytologic and biochemical analyses of peritoneal effusion were suggestive of septic peritonitis. On surgical exploration of the abdomen, the mesenteric vessels had no palpable pulses and they contained gross thromboses. The intestines were white with no visible peristalsis. Necropsy findings included disseminated, poorly differentiated hemangiosarcoma throughout the abdomen. Mesenteric arterioles contained fibrin thrombi. To the author's knowledge, no previous reports exist of complete mesenteric vascular thrombosis associated with disseminated abdominal visceral hemangiosarcoma in a cat.

Evaluation of risk factors for morbidity and mortality after pylorectomy and gastroduodenostomy in dogs.

OBJECTIVES: To (1) identify and describe the type and frequency of postoperative complications after pylorectomy and gastroduodenostomy in dogs and (2) identify preoperative and intraoperative risk factors, including the presence of neoplasia, prognostic for patient mortality after surgery. STUDY DESIGN: Case series. ANIMALS: Dogs (n=24) treated by pylorectomy and gastroduodenostomy. METHODS: Medical records (2000-2007) for 2 teaching hospitals of dogs treated that had pylorectomy and gastroduodenostomy were reviewed. Pre-, intra-, and postoperative data were obtained from the medical record. RESULTS: Of the 24 dogs, 75% survived 14 days, but 10 (41%) died by 3 months. Overall median survival time (MST) was 578 days. On log-rank univariate analysis, preoperative weight loss (P=.001) and malignant neoplasia (P=.01) were associated with decreased survival time. Dogs with malignant neoplasia had a MST of 33 days. Common postoperative morbidity included hypoalbuminemia (62.5%) and anemia (58.3%). CONCLUSIONS: Pylorectomy with gastroduodenostomy has a good short-term outcome but long-term survival time is poor in dogs with malignant neoplasia. CLINICAL RELEVANCE: Overall, most dogs treated with pylorectomy and gastroduodenostomy survived the postoperative period; however, preoperative weight loss and malignant neoplasia were associated with decreased survival time. Because dogs with malignant neoplasia have markedly shortened survival times, pertinent preoperative, diagnostics steps should be exhausted to identify underlying neoplasia.

Outcome following splenectomy in cats.

No studies have yet examined whether there are prognostic factors for survival for cats undergoing splenectomies. The medical records of 19 cats that had complete splenectomy were reviewed for information on preoperative, intraoperative, and postoperative factors. The most common presenting signs were a palpable abdominal mass in 58% and anorexia in 47% of the cats. Mast cell tumors were the most common reason for splenectomy and were found in 10/19 cats (53%); followed by hemangiosarcoma in 4/19 (21%); and lymphoma in 2/19 (11%). The Kaplan-Meier median survival time (MST) was 197 days, with a range from 2 days to 1959 days. Three cats were noted to have preoperative weight loss, and this was the only factor that had prognostic significance for survival following surgery. For cats with weight loss the MST was 3 days, for cats with no weight loss noted the MST was 293 days (P=0.008).