Notch signaling determines cell-fate specification of the two main types of vomeronasal neurons of rodents.

The ability of terrestrial vertebrates to find food and mating partners, and to avoid predators, relies on the detection of chemosensory information. Semiochemicals responsible for social and sexual behaviors are detected by chemosensory neurons of the vomeronasal organ (VNO), which transmits information to the accessory olfactory bulb. The vomeronasal sensory epithelium of most mammalian species contains a uniform vomeronasal system; however, rodents and marsupials have developed a more complex binary vomeronasal system, containing vomeronasal sensory neurons (VSNs) expressing receptors of either the V1R or V2R family. In rodents, V1R/apical and V2R/basal VSNs originate from a common pool of progenitors. Using single cell RNA-sequencing, we identified differential expression of Notch1 receptor and Dll4 ligand between the neuronal precursors at the VSN differentiation dichotomy. Our experiments show that Notch signaling is required for effective differentiation of V2R/basal VSNs. In fact, Notch1 loss of function in neuronal progenitors diverts them to the V1R/apical fate, whereas Notch1 gain of function redirects precursors to V2R/basal. Our results indicate that Notch signaling plays a pivotal role in triggering the binary differentiation dichotomy in the VNO of rodents.

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Elongation of intercostal nerve cutaneous branches for breast and nipple neurotization during breast reconstruction after mastectomy for breast cancer: case-control study.

BACKGROUND: To restore sensation after breast reconstruction, a modified surgical approach was employed by identifying the cut fourth intercostal lateral cutaneous branch, elongating it with intercostal nerve grafts, and coapting it to the innervating nerve of the flap or by using direct neurotization of the spared nipple/skin. METHODS: This was a retrospective case-control study including 56 patients who underwent breast neurotization surgery. Breast operations included immediate reconstruction after nipple-sparing mastectomy (36 patients), skin-sparing mastectomy (8 patients), and delayed reconstruction with nipple preservation (7 patients) or without nipple preservation (5 patients). Patients who underwent breast reconstruction without neurotization were included as the non-neurotization negative control group. The contralateral normal breasts were included as positive controls. RESULTS: The mean(s.d.) monofilament test values were 0.07(0.10) g for the positive control breasts and 179.13(143.31) g for the breasts operated on in the non-neurotization group. Breasts that underwent neurotization had significantly better sensation after surgery, with a mean(s.d.) value of 35.61(92.63) g (P < 0.001). The mean(s.d.) sensory return after neurotization was gradual; 138.17(143.65) g in the first 6 months, 59.55(116.46) g at 7-12 months, 14.54(62.27) g at 13-18 months, and 0.37(0.50) g at 19-24 months after surgery. Two patients had accidental rupture of the pleura, which was repaired uneventfully. One patient underwent re-exploration due to a lack of improvement 1.5 years after neurotization. CONCLUSION: Using the lateral cutaneous branch of the intercostal nerve as the innervating stump and elongating it with intercostal nerve grafts is a suitable technique to restore sensation after mastectomy. This method effectively innervates reconstructed breasts and spares the nipple/skin with minimal morbidity.

Supramolecular Peptoid Structure Strengthens Complexation with Polyacrylic Acid Microgels.

We have studied the complexation between cationic antimicrobials and polyanionic microgels to create self-defensive surfaces that responsively resist bacterial colonization. An essential property is the stable sequestration of the loaded (complexed) antimicrobial within the microgel under a physiological ionic strength. Here, we assess the complexation strength between poly(acrylic acid) [PAA] microgels and a series of cationic peptoids that display supramolecular structures ranging from an oligomeric monomer to a tetramer. We follow changes in loaded microgel diameter with increasing [Na+] as a measure of the counterion doping level. Consistent with prior findings on colistin/PAA complexation, we find that a monomeric peptoid is fully released at ionic strengths well below physiological conditions, despite its +5 charge. In contrast, progressively higher degrees of peptoid supramolecular structure display progressively greater resistance to salting out, which we attribute to the greater entropic stability associated with the complexation of multimeric peptoid bundles.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

Nonpharmacologic and Pharmacologic Treatments of Adults in the Acute Phase of Major Depressive Disorder: A Living Clinical Guideline From the American College of Physicians.

DESCRIPTION: The purpose of this guideline from the American College of Physicians (ACP) is to present updated clinical recommendations on nonpharmacologic and pharmacologic interventions as initial and second-line treatments during the acute phase of a major depressive disorder (MDD) episode, based on the best available evidence on the comparative benefits and harms, consideration of patient values and preferences, and cost. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of the evidence. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes clinicians caring for adult patients in the acute phase of MDD in ambulatory care. The patient population includes adults in the acute phase of MDD. RECOMMENDATION 1A: ACP recommends monotherapy with either cognitive behavioral therapy or a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (strong recommendation; moderate-certainty evidence). RECOMMENDATION 1B: ACP suggests combination therapy with cognitive behavioral therapy and a second-generation antidepressant as initial treatment in patients in the acute phase of moderate to severe major depressive disorder (conditional recommendation; low-certainty evidence). The informed decision on the options of monotherapy with cognitive behavioral therapy versus second-generation antidepressants or combination therapy should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences. RECOMMENDATION 2: ACP suggests monotherapy with cognitive behavioral therapy as initial treatment in patients in the acute phase of mild major depressive disorder (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests one of the following options for patients in the acute phase of moderate to severe major depressive disorder who did not respond to initial treatment with an adequate dose of a second-generation antidepressant: • Switching to or augmenting with cognitive behavioral therapy (conditional recommendation; low-certainty evidence) • Switching to a different second-generation antidepressant or augmenting with a second pharmacologic treatment (see Clinical Considerations) (conditional recommendation; low-certainty evidence) The informed decision on the options should be personalized and based on discussion of potential treatment benefits, harms, adverse effect profiles, cost, feasibility, patients' specific symptoms (such as insomnia, hypersomnia, or fluctuation in appetite), comorbidities, concomitant medication use, and patient preferences.

Quality-of-Life Outcomes in Oral Cancer Patients Reconstructed With Double Free Flaps: A Preoperative and Postoperative Assessment.

PURPOSE: This study aimed to evaluate quality of life (QOL) in patients with locally advanced oral cancer who underwent surgical resection followed by simultaneous double free flap reconstruction. METHODS: Institutional database was reviewed from 2015 to 2021 and prospectively collected University of Washington Quality of Life data that were extracted for patients who met the inclusion criteria. Mean, composite, and best percentage scores were computed. Wilcoxon signed rank test was used to analyze differences between groups. RESULTS: Thirteen patients completed the assessment, all of them being male with a mean follow-up of 2.2 ± 1.2 years. Most common double free flap combination was fibula osteoseptocutaneous flap and anterolateral thigh flap (n = 11). Improvement in pain ( P = 0.01) domain score with decline in speech ( P = 0.01) and taste ( P = 0.02) was noted along with an overall decline in QOL ( P = 0.001) after cancer diagnosis. A decrease in physical function was seen postoperatively. Chewing and saliva were the most cited postoperative patient-reported domain affecting QOL. CONCLUSIONS: In double free flap reconstructed patients, in the postoperative phase, pain scores improved, whereas speech and taste scores declined. The overall health-related QOL declined compared with before cancer diagnosis.

Evaluation of Concomitant Facial Fracture in Traumatic Brain Injury Patients-Simplification and External Validation of a Prediction Model.

BACKGROUND: Patients with traumatic brain injuries (TBIs) often experience concurrent facial bone fractures. In 2021, a prediction model with 10 variables was published and precisely predicted concomitant facial fractures in TBI patients. Herein, external validation and simplification of this model was performed. METHODS: Traumatic brain injury patients treated at a major referral trauma center were retrospectively reviewed for 1 year. The original prediction model (published in 2021), which was developed from a rural level II trauma center, was applied for external validation. A new and simplified model from our level I trauma center was developed and backwardly validated by rural level II trauma center data. RESULTS: In total, 313 TBI patients were enrolled; 101 (32.3%) had concomitant facial fractures. When the previous prediction model was applied to the validation cohort, it achieved acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.713 and good precision, with a Brier score of 0.083. A new and simplified model with 6 variables (age, tooth rupture, epistaxis, facial lesion, eye injury, and intracranial hemorrhage) was created with excellent discrimination (AUC = 0.836) and good precision (Brier score of 0.055). The backward validation of this new model also showed excellent discrimination in the cohort used to develop the original model (AUC = 0.875). CONCLUSION: The original model provides an acceptable and reproducible prediction of concomitant facial fractures among TBI patients. A simplified model with fewer variables and the same accuracy could be applied in the emergency department and at higher- and lower-level trauma centers.

Improved Pain and Function With Triamcinolone Acetonide Extended-Release and Cryoneurolysis for Knee Osteoarthritis: Use of a New Real-World Registry.

BACKGROUND: Knee osteoarthritis (OA) affects 19% of American adults aged more than 45 years and costs $27+ billion annually. A wide range of nonoperative treatment options are available. This study compared 6 treatments: cryoneurolysis with deep genicular nerve block (Cryo-Deep/Both), cryoneurolysis with superficial nerve block (Cryo-Superficial), intra-articular hyaluronic acid (IA-HA) injections, nonsteroidal anti-inflammatory drug injections (IA-NSAIDs), IA-corticosteroids (IA-CS) injections, or IA-triamcinolone extended release (IA-TA-ER) injections over 4 months for: (1) pain severity and analgesic use; and (2) physical function (from Knee Injury and Osteoarthritis Outcome Score for Joint Replacement). METHODS: Patients who had unilateral knee OA and received nonoperative intervention were enrolled in the Innovations in Genicular Outcomes Research registry, a novel, multicenter real-world registry, between September 2021 and February 2024. A total of 480 patients were enrolled. Both pain and functional outcomes were assessed at baseline, weekly, and monthly, which were analyzed by overall trend, magnitude changes pretreatment to post-treatment, and distribution-based minimally clinically important difference (MCID) score. Multivariate linear regressions with adjustments for 7 confounding factors were used to compare follow-up outcomes among 6 treatment groups. RESULTS: Use of IA-TA-ER injections was associated with the lowest pain, greatest pain reduction, and highest prevalence of patients achieving MCID relative to other treatments (P < .001). Deep/Both-Cryo and IA-CS were associated with a higher prevalence of achieving MCID than IA-HA, IA-NSAIDs, and Cryo-Superficial (P ≤ .001). Use of IA-TA-ER was also associated with the greatest functional score, improvement from baseline, and highest prevalence of patients achieving MCID than other treatments (P ≤ .003). CONCLUSIONS: The IA-TA-ER appears to outperform other treatments in terms of pain relief and functional improvement for up to 4 months following treatment. In addition, outcomes in the novel cryoneurolysis and conventional IA-CS were similar to one another and better than those in IA-HA and IA-NSAIDs.

Cryoneurolysis Associated With Improved Pain, Function, and Sleep in Patients Following total Knee Arthroplasty: Use of a New Real-World Registry.

BACKGROUND: Total knee arthroplasty (TKA) is performed on approximately 790,000 patients annually in the United States and is projected to increase to 1.5 million by 2050. This study aimed at assessing the use of preoperative cryoneurolysis on patients undergoing TKA by analyzing: (1) pain severity; (2) opioid use; (3) functional status; and (4) sleep disturbance (SD) over 6 months following discharge. METHODS: Patients enrolled in the Innovations in Genicular Outcomes Registry between September 2021 and February 2024 were followed for 6 months. Our analyses included patients undergoing unilateral primary TKA with no preoperative opioid prescription, who either received cryoneurolysis, or did not. Baseline patient demographics were collected before TKA and tabulated. Pain management was assessed via the Brief Pain Inventory-Short Form instrument for pain severity. SD was measured using the patient-reported outcomes measurement information system questionnaire. Each outcome measure was assessed prior to TKA, weekly, and at monthly follow-up. Data were analyzed by a generalized linear mixed-effect regression model to compare cryoneurolysis versus control patients, with a P < .05 as significant. RESULTS: There were 80 patients who were treated with preoperative cryoneurolysis, while 60 control patients did not have treatment. Patients receiving cryoneurolysis experienced significantly lower pain severity and SD over the 6-month follow-up than control patients (P = .046). Cryoneurolysis was also associated with a trend toward greater functional improvement that did not reach statistical significance (P = .061). Further, patients who underwent cryoneurolysis were 72% less likely than control group patients to take opioids over 6 months following discharge (P < .001). CONCLUSIONS: Preoperative cryoneurolysis therapy in opioid-naive patients undergoing TKA is associated with improved pain, decreased opioid use, and improved SD for 6 months postoperatively. Cryoneurolysis, a nonopioid pain relief modality administered preoperatively, demonstrated substantial benefits in patients who underwent TKA.

Sequential free fibula transfers: Quality of life and systematic review.

BACKGROUND: Successive osteoseptocutaneous fibula transfers for jaws reconstruction are rare but important options. This study contributes patient-reported and clinical outcomes, as well as systematically reviews all existing reports. METHODS: All sequential fibula transfers performed by the senior author were reviewed from a prospectively managed database, including University of Washington quality of life (UWQoL). Systematic review was conducted in PubMed and Cochrane databases for similar publications. RESULTS: Eighteen patients (average age 51.5 years) received sequential fibulas (mean 4.7 years between reconstructions). Secondary fibulas more often had benign indications (72.2% vs. 33.3%, p = .04), most commonly osteoradionecrosis (38.9%). At a mean follow-up of 30.5 months, the average interincisal distance increased from 21.8 to 27.6 mm, and 92.3% tolerated an oral diet following the second fibula. Eight patients completed the UW-QoL before and after the second fibula, and three prior to the first fibula. Composite physical function was significantly decreased from 96.7 prefibula reconstruction to 63.3 following the first (p < .001) and 64.2 after the second fibula (p < .001). There were no differences in other domains. The systematic review yielded six articles reporting 56 patients (mean 39 months between fibulas). Secondary fibulas were performed for repeat malignancy (45%) and osteoreadionecrosis (39%), resulting in elevated tube feeding from 20% following the first to 39% following the second, but overall high quality of life in two studies. CONCLUSIONS: Sequential osteoseptocutaneous fibula reconstructions of jaws are often performed for benign indications such as osteoradionecrosis. Overall function and QoL are comparable with those following the first fibula transfer.

Between good and evil: Complexation of the human cathelicidin LL-37 with nucleic acids.

The innate immune system provides a crucial first line of defense against invading pathogens attacking the body. As the only member of the human cathelicidin family, the antimicrobial peptide LL-37 has been shown to have antiviral, antifungal, and antibacterial properties. In complexation with nucleic acids, LL-37 is suggested to maintain its beneficial health effects while also acting as a condensation agent for the nucleic acid. Complexes formed by LL-37 and nucleic acids have been shown to be immunostimulatory with a positive impact on the human innate immune system. However, some studies also suggest that in some circumstances, LL-37/nucleic acid complexes may be a contributing factor to autoimmune disorders such as psoriasis and systemic lupus erythematosus. This review provides a comprehensive discussion of research highlighting the beneficial health effects of LL-37/nucleic acid complexes, as well as discussing observed detrimental effects. We will emphasize why it is important to investigate and elucidate structural characteristics, such as condensation patterns of nucleic acids within complexation, and their mechanisms of action, to shed light on the intricate physiological effects of LL-37 and the seemingly contradictory role of LL-37/nucleic acid complexes in the innate immune response.

Smad4-dependent morphogenic signals control the maturation and axonal targeting of basal vomeronasal sensory neurons to the accessory olfactory bulb.

The vomeronasal organ (VNO) contains two main types of vomeronasal sensory neurons (VSNs) that express distinct vomeronasal receptor (VR) genes and localize to specific regions of the neuroepithelium. Morphogenic signals are crucial in defining neuronal identity and network formation; however, if and what signals control maturation and homeostasis of VSNs is largely unexplored. Here, we found transforming growth factor ß (TGFß) and bone morphogenetic protein (BMP) signal transduction in postnatal mice, with BMP signaling being restricted to basal VSNs and at the marginal zones of the VNO: the site of neurogenesis. Using different Smad4 conditional knockout mouse models, we disrupted canonical TGFß/BMP signaling in either maturing basal VSNs (bVSNs) or all mature VSNs. Smad4 loss of function in immature bVSNs compromises dendritic knob formation, pheromone induced activation, correct glomeruli formation in the accessory olfactory bulb (AOB) and survival. However, Smad4 loss of function in all mature VSNs only compromises correct glomeruli formation in the posterior AOB. Our results indicate that Smad4-mediated signaling drives the functional maturation and connectivity of basal VSNs.

Simulations of rate of genetic gain in dry bean breeding programs.

KEY MESSAGE: A reference study for breeders aiming at maximizing genetic gain in common bean. Depending on trait heritability and genetic architecture, conventional approaches may provide an advantage over other frameworks. Dry beans (Phaseolus vulgaris L.) are a nutrient dense legume that is consumed by developed and developing nations around the world. The progress to improve this crop has been quite steady. However, with the continued rise in global populations, there are demands to expedite genetic gains. Plant breeders have been at the forefront at increasing yields in the common bean. As breeding programs are both time-consuming and resource intensive, resource allocation must be carefully considered. To assist plant breeders, computer simulations can provide useful information that may then be applied to the real world. This study evaluated multiple breeding scenarios in the common bean and involved five selection strategies, three breeding frameworks, and four different parental population sizes. In addition, the breeding scenarios were implemented in three different traits: days to flowering, white mold tolerance, and seed yield. Results from the study reflect the complexity of breeding programs, with the optimal breeding scenario varying based on trait being selected. Relative genetic gains per cycle of up to 8.69% for seed yield could be obtained under the use of the optimal breeding scenario. Principal component analyses revealed similarity between strategies, where single seed descent and the modified pedigree method would often aggregate. As well, clusters in the direction of the Hamming distance eigenvector are a good indicator of poor performance in a strategy.

Putting Evidence Into Practice: An Update on the US Preventive Services Task Force Methods for Developing Recommendations for Preventive Services.

PURPOSE: The US Preventive Services Task Force (USPSTF) is an independent body that makes evidence-based recommendations regarding preventive services to improve health for people nationwide. Here, we summarize current USPSTF methods, describe how methods are evolving to address preventive health equity, and define evidence gaps for future research. METHODS: We summarize current USPSTF methods as well as ongoing methods development. RESULTS: The USPSTF prioritizes topics on the basis of disease burden, extent of new evidence, and whether the service can be provided in primary care and going forward will increasingly consider health equity. Analytic frameworks specify the key questions and linkages connecting the preventive service to health outcomes. Contextual questions provide information on natural history, current practice, health outcomes in high-risk groups, and health equity. The USPSTF assigns a level of certainty to the estimate of net benefit of a preventive service (high, moderate, or low). The magnitude of net benefit is also judged (substantial, moderate, small, or zero/negative). The USPSTF uses these assessments to assign a letter grade from A (recommend) to D (recommend against). I statements are issued when evidence is insufficient. CONCLUSIONS: The USPSTF will continue to evolve its methods for simulation modeling and to use evidence to address conditions for which there are limited data for population groups who bear a disproportionate burden of disease. Additional pilot work is underway to better understand the relations of the social constructs of race, ethnicity, and gender with health outcomes to inform the development of a USPSTF health equity framework.

Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the role of colonoscopy for diagnostic evaluation of colorectal cancer (CRC) after a presumed diagnosis of acute left-sided colonic diverticulitis and on the role of pharmacologic, nonpharmacologic, and elective surgical interventions to prevent recurrence after initial treatment of acute complicated and uncomplicated left-sided colonic diverticulitis. This guideline is based on the current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee (CGC) based these recommendations on a systematic review on the role of colonoscopy after acute left-sided colonic diverticulitis and pharmacologic, nonpharmacologic, and elective surgical interventions after initial treatment. The systematic review evaluated outcomes rated by the CGC as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with recent episodes of acute left-sided colonic diverticulitis. RECOMMENDATION 1: ACP suggests that clinicians refer patients for a colonoscopy after an initial episode of complicated left-sided colonic diverticulitis in patients who have not had recent colonoscopy (conditional recommendation; low-certainty evidence). RECOMMENDATION 2: ACP recommends against clinicians using mesalamine to prevent recurrent diverticulitis (strong recommendation; high-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either uncomplicated diverticulitis that is persistent or recurs frequently or complicated diverticulitis (conditional recommendation; low-certainty evidence). The informed decision whether or not to undergo surgery should be personalized based on a discussion of potential benefits, harms, costs, and patient's preferences.

Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to provide clinical recommendations on the diagnosis and management of acute left-sided colonic diverticulitis in adults. This guideline is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. METHODS: The ACP Clinical Guidelines Committee (CGC) developed this guideline based on a systematic review on the use of computed tomography (CT) for the diagnosis of acute left-sided colonic diverticulitis and on management via hospitalization, antibiotic use, and interventional percutaneous abscess drainage. The systematic review evaluated outcomes that the CGC rated as critical or important. This guideline was developed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. TARGET AUDIENCE AND PATIENT POPULATION: The target audience is all clinicians, and the target patient population is adults with suspected or known acute left-sided colonic diverticulitis. RECOMMENDATION 1: ACP suggests that clinicians use abdominal CT imaging when there is diagnostic uncertainty in a patient with suspected acute left-sided colonic diverticulitis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2: ACP suggests that clinicians manage most patients with acute uncomplicated left-sided colonic diverticulitis in an outpatient setting (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians initially manage select patients with acute uncomplicated left-sided colonic diverticulitis without antibiotics (conditional recommendation; low-certainty evidence).

Phrenic Nerve as an Alternative Donor for Nerve Transfer to Restore Shoulder Abduction in Severe Multiple Root Injuries of the Adult Brachial Plexus.

PURPOSE: Nerve transfer is the gold standard to restore shoulder abduction in acute brachial plexus injuries. The aim of this study was to compare the phrenic nerve (Ph) to the spinal accessory nerve (XI) as the donor nerve for this purpose. METHODS: A retrospective chart review was performed on 136 patients with acute brachial plexus injuries who received a nerve transfer of the shoulder with either the Ph (94 patients) or XI (42 patients). Each group was divided into 3 subgroups based on the recipient nerve. The maximum degree of shoulder abduction was recorded after 2 years of postoperative follow-up. A generalized estimating equation model was performed to examine the variables affecting shoulder abduction over time. RESULTS: The maximum degrees of shoulder abduction achieved were 61.9° ± 38.7° in patients with Ph and 51.1° ± 37.3° in patients with XI. More than M3 shoulder abduction was achieved by 67% of patients with Ph versus 59% of patients with XI. The regression analysis showed that the age at the time of surgery correlated more with the functional outcome over time than the choice of donor nerve. CONCLUSIONS: In multiple root brachial plexus injuries, the Ph exhibited similar outcomes to the XI for shoulder abduction. Our routine exploration of the supraclavicular plexus exposes the Ph conveniently for nerve transfer. The phrenic nerve should be considered as an alternative when the XI is not available or is reserved for secondary reconstruction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Skin Cancer Screening: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Skin cancer is the most common cancer type and is a major cause of morbidity. Objective: To systematically review the benefits and harms of screening for skin cancer to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from June 1, 2015, through January 7, 2022; surveillance through December 16, 2022. Study Selection: English-language studies conducted in asymptomatic populations 15 years or older. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant data from fair- or good-quality studies; results were narratively summarized. Main Outcomes and Measures: Morbidity; mortality; skin cancer stage, precursor lesions, or lesion thickness at detection; harms of screening. Results: Twenty studies in 29 articles were included (N = 6 053 411). Direct evidence on screening effectiveness was from 3 nonrandomized analyses of 2 population-based skin cancer screening programs in Germany (n = 1 791 615) and suggested no melanoma mortality benefit at the population level over 4 to 10 years' follow-up. Six studies (n = 2 935 513) provided inconsistent evidence on the association between clinician skin examination and lesion thickness or stage at diagnosis. Compared with usual care, routine clinician skin examination was not associated with increased detection of skin cancer or precursor lesions (5 studies) or stage at melanoma detection (3 studies). Evidence on the association between clinician skin examination and lesion thickness at detection was inconsistent (3 studies). Nine studies (n = 1 326 051) found a consistent positive association between more advanced stage at melanoma detection and increasing risk of melanoma-associated and all-cause mortality. Two studies (n = 232) found little to no persistent cosmetic or psychosocial harms associated with screening. Conclusions and Relevance: A substantial nonrandomized evidence base suggests a clear association between earlier stage at skin cancer detection and decreased mortality risk. However, nonrandomized studies suggest little to no melanoma mortality benefit associated with skin cancer screening with visual skin examination in adolescents or adults and no association between routine clinician skin examination and earlier stage at melanoma detection. Evidence is inconsistent regarding whether clinician skin examination is associated with thinner melanoma lesions at detection.