"Feed-and-wrap" technique versus deep sedation for neonatal magnetic resonance imaging: a retrospective comparative study.

OBJECTIVES: Neonatal MRI is usually performed under deep sedation, which is challenging-especially in low-weight premature patients. In addition, long-term side effects, such as neurotoxicity, are of concern. An alternative to sedation is to induce natural sleep by feeding and immobilising the child, the "feed-and-wrap" technique (FWT). The objective of this study was to evaluate differences in image quality between neonates examined under sedation and by using the FWT during the first four months of life. MATERIALS AND METHODS: We retrospectively assessed image quality (based on a 4-point semiquantitative scale) of all MRI examinations in neonates performed at our institution between July 2009 and August 2022. Differences in image quality between examinations under sedation versus FWT were evaluated. RESULTS: We included 432 consecutive patients, 243 (56%) using sedation and 189 (44%) using the FWT. Corrected age and body weight (mean ± SD: 3.7 ± 1.1 versus 4.5 ± 1.3 kg, p < 0.001) were significantly lower in the FWT group. The overall success rate in the FWT group was 95%. Image quality was slightly lower when using the FWT (mean ± SD: 3.7 ± 0.43 versus 3.96 ± 0.11, p < 0.001). Multivariate analysis showed a higher risk of acquiring sequences with diagnostic limitations in the FWT group (p < 0.001), increasing with corrected age (p = 0.048). CONCLUSION: The FWT is a highly successful method to perform MRI scans in term and preterm neonates. Overall image quality is only slightly lower than under sedation. Especially in immature low-weight preterm patients, the FWT is a reliable option to perform MRI studies without exposing the child to risks associated with sedation. CLINICAL RELEVANCE STATEMENT: The "feed-and-wrap" technique enables high-quality MRI examinations in neonates, including low-weight premature patients. Deep sedation for diagnostic MRI procedures in this age group, which has the risk of short- and long-term complications, can often be avoided. KEY POINTS: Deeply sedating neonates for MR examinations comes with risks. Image quality is only slightly lower when using the "feed-and-wrap" technique. The "feed-and-wrap" technique is feasible even in low-weight premature infants.

Autonomic activity, posttraumatic and nontraumatic nightmares, and PTSD after trauma exposure.

BACKGROUND: Nightmares are a hallmark symptom of posttraumatic stress disorder (PTSD). This strong association may reflect a shared pathophysiology in the form of altered autonomic activity and increased reactivity. Using an acoustic startle paradigm, we investigated the interrelationships of psychophysiological measures during wakefulness and PTSD diagnosis, posttraumatic nightmares, and nontraumatic nightmares. METHODS: A community sample of 122 trauma survivors were presented with a series of brief loud tones, while heart rate (HRR), skin conductance (SCR), and orbicularis oculi electromyogram (EMGR) responses were measured. Prior to the tone presentations, resting heart rate variability (HRV) was assessed. Nightmares were measured using nightmare logs. Three dichotomous groupings of participants were compared: (1) current PTSD diagnosis (n = 59), no PTSD diagnosis (n = 63), (2) those with (n = 26) or without (n = 96) frequent posttraumatic nightmares, and (3) those with (n = 22) or without (n = 100) frequent nontraumatic nightmares. RESULTS: PTSD diagnosis was associated with posttraumatic but not with nontraumatic nightmares. Both PTSD and posttraumatic nightmares were associated with a larger mean HRR to loud tones, whereas nontraumatic nightmare frequency was associated with a larger SCR. EMGR and resting HRV were not associated with PTSD diagnosis or nightmares. CONCLUSIONS: Our findings suggest a shared pathophysiology between PTSD and posttraumatic nightmares in the form of increased HR reactivity to startling tones, which might reflect reduced parasympathetic tone. This shared pathophysiology could explain why PTSD is more strongly related to posttraumatic than nontraumatic nightmares, which could have important clinical implications.

A case of severe, irreversible hypocalcemia after one dose of pamidronate administered for hypercalcemia of malignancy.

This is a case report of a patient who developed severe, irreversible hypocalcemia after receiving one dose of pamidronate 90 mg for hypercalcemia of malignancy. Hypocalcemia is a known risk of bisphosphonate treatments, but the incidence of severe hypocalcemia is rare, and the risk factors are well established. However, in the treatment of hypercalcemia of malignancy, the treatment objective is to reduce the elevated serum calcium level, and the bisphosphonate is usually given as one time dose only. The potential for developing severe hypocalcemia may not be considered a significant concern in this setting compared to the setting of the treatment of bone metastasis, where the baseline serum calcium level is not elevated and the bisphosphonate is administered at a regular interval of every three to four weeks. Furthermore, there is unawareness of prevalence of vitamin D deficiency in cancer patients, especially in those with advanced cancer, which may lead to inadvertent, severe hypocalcemia from bisphosphonate treatment. The objective of this case report is to bring awareness to the risk of severe hypocalcemia in patients with hypercalcemia of malignancy and the high prevalence of unrecognized vitamin D deficiency in cancer patients.

Clinical anatomic considerations of the zygomaticus minor muscle based on the morphology and insertion pattern.

BACKGROUND: The zygomaticus minor muscle (Zmi) is involved in the expression of many different facial emotions. However, the details of its insertion pattern and morphology are not well described. OBJECTIVE: The aim of this study was to clarify the morphology and insertion pattern of the Zmi, and to provide clinical anatomic information that will help elucidate its roles in animation. MATERIALS AND METHODS: Fifty-four embalmed adult hemifaces (18 men and 12 women; mean age, 67.4 years) from 30 cadavers were used in this study. The dissection was performed with the aid of a surgical microscope. RESULTS: This muscle could be classified into 3 types (A-C). Type A, in which the Zmi attached only to the upper lip, was observed in 63.0% of cases (34/54) and could be subdivided into 2 types: straight (A-1; 31.5%, 17 cases) and curved (A-2; 31.5%, 17 cases). Type B, in which the Zmi was attached to both the upper lip and the lateral alar region, occurred in 27.8% of cases (15/54). In Type C (9.2% of cases, 5/54), there was either no or only undeveloped Zmi fibers. CONCLUSION: The present finding of Zmi fibers being attached to the alar region in many cases (27.8%) suggests that this muscle is involved in elevation of both the nose ala and upper lip during various facial animations.

Human Papillomavirus as Non-Traditional Cardiovascular Risk Factors: Fact or Fiction? Part 1.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and worldwide, with more than 42 million Americans infected with types of HPV that are known to cause disease. While the link between HPV and the development of a variety of cancers has been strongly established, recent literature has demonstrated a potential association between HPV and increased risk of cardiovascular disease. Nevertheless, despite plausible mechanisms for the development of cardiovascular disease with HPV infection, a causative relationship has yet to be firmly established, in part due to potential confounding risk factors between the two. In this 2-part series, we discuss the emerging relationship between HPV and cardiovascular disease. In part 1, we focus on the pathophysiology of HPV infection and potential mechanisms for the development of cardiovascular disease.

Acute Myocardial Infarction in Pregnancy.

Pregnancy-associated myocardial infarction is an overall uncommon event, but can be associated with significant maternal and fetal morbidity and mortality. In contrast to myocardial infarction in the general nonpregnant population, the mechanism of pregnancy-associated myocardial infarction is most commonly due to nonatherosclerotic mechanisms such as coronary dissection, vasospasm, or thromboembolism. The diagnosis of pregnancy-associated myocardial infarction can be challenging, requiring a high index of suspicion for prompt recognition and management. Furthermore, the management of pregnancy-associated myocardial infarction can be complex due to maternal and fetal considerations and may vary based on the specific underlying mechanism of the myocardial infarction. This review aims to review the recent literature on pregnancy-associated myocardial infarction and summarize the epidemiology, mechanisms, diagnosis, and treatment strategies for this uncommon entity.

Classification of Maxillofacial Morphology by Artificial Intelligence Using Cephalometric Analysis Measurements.

The characteristics of maxillofacial morphology play a major role in orthodontic diagnosis and treatment planning. While Sassouni's classification scheme outlines different categories of maxillofacial morphology, there is no standardized approach to assigning these classifications to patients. This study aimed to create an artificial intelligence (AI) model that uses cephalometric analysis measurements to accurately classify maxillofacial morphology, allowing for the standardization of maxillofacial morphology classification. This study used the initial cephalograms of 220 patients aged 18 years or older. Three orthodontists classified the maxillofacial morphologies of 220 patients using eight measurements as the accurate classification. Using these eight cephalometric measurement points and the subject's gender as input features, a random forest classifier from the Python sci-kit learning package was trained and tested with a k-fold split of five to determine orthodontic classification; distinct models were created for horizontal-only, vertical-only, and combined maxillofacial morphology classification. The accuracy of the combined facial classification was 0.823 ± 0.060; for anteroposterior-only classification, the accuracy was 0.986 ± 0.011; and for the vertical-only classification, the accuracy was 0.850 ± 0.037. ANB angle had the greatest feature importance at 0.3519. The AI model created in this study accurately classified maxillofacial morphology, but it can be further improved with more learning data input.

A fatal case of Pneumocystis jirovecii pneumonia in a breast cancer patient receiving weekly paclitaxel and trastuzumab.

Pneumocystis jirovecii (formerly carinii) pneumonia (PJP) is an opportunistic infection well-recognized in patients with profound T cell immunodeficiency. It is much less common in patients with solid tumors unless they have other major predisposing factors such as prolonged treatment with corticosteroids or T4 lymphocyte counts of less than 200 cells/mm(3). We present a previously unreported case of fatal PJP in a breast cancer patient with bone metastases who was receiving a first-line treatment with weekly paclitaxel, trastuzumab, and dexamethasone as premedication for paclitaxel. She had received eight doses of paclitaxel at 80 mg/m(2), trastuzumab 2 mg/m(2), and dexamethasone 10 mg for just over 7 weeks when she was diagnosed with PJP. While the patient's granulocyte counts were normal throughout her treatment, the total lymphocyte counts reached the nadir of 400 cells/mm(3) a few days after the eighth dose of chemotherapy - around the time of PJP diagnosis. Both dexamethasone and the total lymphocyte nadir predisposed this patient to PJP.

Chemotherapy-induced infiltrative pneumonitis cases in breast cancer patients.

A number of chemotherapy drugs are well known to cause various histopathologic patterns of lung injury. The incidence of chemotherapy-induced infiltrative pneumonitis is rare and the diagnosis is difficult due to the nonspecific clinical and radiological presentations. However, it can cause significant morbidity and mortality in cancer patients. There is no consensus on the treatment of this adverse event, but prompt diagnosis and intervention is important as fatal outcomes have been reported. We present five cases of chemotherapy-induced infiltrative pneumonitis in breast cancer patients involving docetaxel, paclitaxel, gemcitabine and cyclophosphamide.

Sensor-Based Nerve Compression Measurement: A Scoping Review of Current Concepts and a Preclinical Evaluation of Commercial Microsensors.

Background: Chronic nerve compression is the most common indication for nerve surgery. However, the clinical diagnosis still relies on surrogate parameters since devices for direct nerve compression pressure measurement (DNCPM) are clinically unavailable yet. Objectives: To review previous approaches to DNCPM and evaluate presently available microsensor systems for their feasibility and reliability in preclinical nerve compression models. Methods: A scoping literature review was conducted in accordance with the PRISMA-ScR guidelines. A subsequent market research aimed at identifying commercially available sensor systems potentially suitable for DNCPM. Sensors were evaluated for feasibility and safety of perineural sensor positioning, tissue compatibility and measurement reliability in a synthetic nerve compression model and an ex-vivo chicken leg model. Results: A scoping literature review identified 197 potentially eligible studies of which 65 were included in the analysis. Previous approaches to DNCPM predominantly used pressure sensing catheters designed for fluid- or intra-compartmental pressure measurement. A market research identified two piezoresistive sensor systems (IntraSense, SMi, United States; Mikro-Cath, Millar, United States) as potentially suitable for intraoperative DNCPM. In both preclinical models, the detected compression pressure differed significantly between sensors and systems showed substantial measurement variability with a median percent coefficient of variation between 15.5% and 32%. Sensor position was accountable for up to 99.1% of the variance. Conclusion: Measurement variability caused by unreliable sensor positioning is a key limitation of presently available sensors when applied for nerve compression measurements. Redesigned systems with small, flat-shaped and longitudinally oriented sensors and dedicated introducers would facilitate sensor positioning and therefore may allow for reliable measurements.

Interleukin-1ß and tumor necrosis factor are essential in controlling an experimental orthopedic implant-associated infection.

Orthopedic implant-associated infection (OIAI) is a major complication that leads to implant failure. In preclinical models of Staphylococcus aureus OIAI, osteomyelitis and septic arthritis, interleukin-1α (IL-1α), IL-1ß, and tumor necrosis factor (TNF) are induced, but whether they have interactive or distinctive roles in host defense are unclear. Herein, a S. aureus OIAI model was performed in mice deficient in IL-1α, IL-1ß, or TNF. Mice deficient in IL-1ß or TNF (to a lesser extent) but not IL-1α had increased bacterial burden at the site of the OIAI throughout the 28-day experiment. IL-1ß and TNF had a combined and critical role in host defense as mice deficient in both IL-1R and TNF (IL-1R/TNF-deficient mice) had a 40% mortality rate, which was associated with markedly increased bacterial burden at the site of the OIAI infection. Finally, IL-1α- and IL-1ß-deficient mice had impaired neutrophil recruitment whereas IL-1ß-, TNF-, and IL-1R/TNF-deficient mice all had impaired recruitment of both neutrophils and monocytes. Therefore, IL-1ß and TNF contributed to host defense against S. aureus OIAI and neutrophil recruitment was primarily mediated by IL-1ß and monocyte recruitment was mediated by both IL-1ß and TNF.

In vivo delivery of synthetic DNA-encoded antibodies induces broad HIV-1-neutralizing activity.

Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased neutralization breadth. Two dmAbs, PGDM1400 and PGT121, were advanced into nonhuman primates for study. High peak-circulating levels (between 6 and 34 µg/ml) of these dmAbs were measured, and the sera of all animals displayed broad neutralizing activity. The dmAb approach provides an important local delivery platform for the in vivo generation of HIV-1 bNAbs and for other infectious disease antibodies.

A pan-genotypic Hepatitis C Virus NS5A amplification method for reliable genotyping and resistance testing.

BACKGROUND: Chronic infection with the Hepatitis C Virus (HCV) is associated with the risk of progressive liver disease. Although, HCV treatment options and viral cure rates have tremendously increased over the last decade, all currently licensed combination therapies contain inhibitors of the replication complex NS5A. Resistance-associated substitutions (RAS) in NS5A can limit the efficacy of therapy; however, resistance testing is routinely not recommended for all patients. Notably, pan-genotypic combinations have been approved, however the correct identification of the HCV genotype is still required for treatment decisions and is a good predictor for treatment success. OBJECTIVE: The aim of this study was the establishment of a pan-genotypic NS5A amplification method for reliable genotyping and simultaneous resistance testing in a fast and cheap routine diagnostic setup. STUDY DESIGN: Pan-genotypic degenerated nested PCR primer were designed and tested in 262 HCV-patients. The collection included samples from genotypes 1-7 and the median viral load was 1.07 × 106 IU/ml (range 248-21 × 106 IU/ml). RESULTS: Amplification of the expected 747bp fragment was successful in 257 of 262 (98.1%) samples including samples <1000 IU/ml. The direct comparison of the genotype information obtained with core sequencing to those obtained by NS5A prediction showed high concordance (97.3%) and discrepancies occurred only for relatively rare subtypes. Resistance analysis using Geno2Pheno[HCV] showed NS5A-RAS in 23 of 257 (8.9%) of samples. CONCLUSIONS: We successfully developed a routine diagnostic method for pan-genotypic amplification of NS5A. This amplicon can be used for simultaneous genotyping and resistance testing for enhancing and improving routine HCV diagnostic.

Influenza vaccination for immunocompromised patients: summary of a systematic review and meta-analysis.

Vaccination of immunocompromised patients is recommended in many national guidelines to protect against severe or complicated influenza infection. However, due to uncertainties over the evidence base, implementation is frequently patchy and dependent on individual clinical discretion. We conducted a systematic review and meta-analysis to assess the evidence for influenza vaccination in this patient group. Healthcare databases and grey literature were searched and screened for eligibility. Data extraction and assessments of risk of bias were undertaken in duplicate, and results were synthesised narratively and using meta-analysis where possible. Our data show that whilst the serological response following vaccination of immunocompromised patients is less vigorous than in healthy controls, clinical protection is still meaningful, with only mild variation in adverse events between aetiological groups. Although we encountered significant clinical and statistical heterogeneity in many of our meta-analyses, we advocate that immunocompromised patients should be targeted for influenza vaccination.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

BACKGROUND: Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. METHODOLOGY/PRINCIPAL FINDINGS: Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; p<0.001) and laboratory confirmed influenza infection (OR=0.15; 95% CI=0.03-0.63; p=0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. CONCLUSIONS/SIGNIFICANCE: Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.