bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Immune Checkpoint Inhibitor-associated Myocarditis
Authors: Heemelaar Julius C. , Louisa Maria , Neilan Tomas G.
Published: July 2023

Immune checkpoint inhibitors (ICIs) are a form immunotherapy where the negative regulators of host immunity are targeted, thereby leveraging the own immune system. ICIs have significantly improved cancer survival in several advanced malignancies, and there are currently more than 90 different cancer indications for ICIs. Most patients develop immune-related adverse events during ICI therapy. Most are mild, but a small subset of patients will develop severe and potentially fatal immune-related adverse events. A serious cardiovascular complication of ICI therapy is myocarditis. Although the incidence of myocarditis is low, mortality rates of up to 50% have been reported. The mainstay of ICI-associated myocarditis treatment is high-dose corticosteroids. Unfortunately, half of patients with myocarditis do not show clinical improvement after corticosteroid treatment. Also, high doses of corticosteroids may adversely impact cancer outcomes. There is an evidence gap in the optimal second-line treatment strategy. Currently, there is a paradigm shift in second-line treatment taking place from empirical corticosteroid-only strategies to either intensified initial immunosuppression where corticosteroids are combined with another immunosuppressant or targeted therapies directed at the pathophysiology of ICI myocarditis. However, the available evidence to support these novel strategies is limited to observational studies and case reports. The aim of this review is to summarize the literature, guidelines, and future directions on the pharmacological treatment of ICI myocarditis.
Oral Oncolytics and Cardiovascular Risk Management and Monitoring
Authors: White Raechel T. , Sirek Marie E. , Marrs Joel C.
Published: July 2023

Oral oncolytic treatment options have expanded over the last decade and have brought to light the need to monitor and manage cardiovascular (CV) disease in patients being treated with these therapies. There is a need to assess CV risk before patients receive oral oncolytic therapy with known potential to cause negative CV sequelae such as left ventricular dysfunction, hypercholesterolemia, hypertension, and arrhythmias. The review highlights the need to evaluate traditional CV risk factors and their association with the development and progression of cancer. In addition, this review suggests approaches to monitor for CV adverse events and manage CV disease during and after treatment with oral oncolytic therapy. Key guideline recommendations are reviewed and highlight specific approaches to minimize CV harm for patients exposed to oral oncolytic therapy. Careful monitoring and patient-centered decision making are key in choosing appropriate therapies. A multidisciplinary approach between oncologists, cardio-oncologists, pharmacists, and other members of the health care team is essential in navigating cardiac toxicities.
The Use of Botulinum Toxin in the Management of Hidradenitis Suppurativa: A Systematic Review
Authors: Geoghegan Luke , Rodrigues Raina , Harrison Conrad J. , Rodrigues Jeremy N.
Published: July 2023

Background:

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by suppurative infection, sinus tract, and abscess formation. International management guidelines are largely consensus-based. Botulinum toxin (BTX) has been widely used in the treatment of apocrine and eccrine gland disorders, such as hyperhidrosis, although the effectiveness of BTX in the treatment of HS remains unknown. The aim of this systematic review was to understand the published evidence of BTX safety and effectiveness in the management of HS.

Methods:

We conducted a PRISMA-compliant, prospectively registered (PROSPERO, CRD42021228732), systematic review. We devised bespoke search strategy and applied it to the Cochrane Central Register of Controlled Trials, Medline, Embase, and OpenGrey up until March 2022. We included all clinical studies that reported outcomes following BTX treatment in patients diagnosed with HS (both adult and pediatric).

Results:

A total of 4658 studies were identified, of which six met full inclusion criteria reporting data on 26 patients. The six identified studies included one randomized control trial, one case series, and four case studies. The one included randomized control trial demonstrated a significant reduction in the Dermatology Life Quality Index score at 3 months following treatment with BTX.

Conclusions:

The effectiveness and safety of BTX in the treatment of HS remain unknown. This systematic review identified a paucity of high-quality clinical data. Evidence of treatment effectiveness is likely to come from registry-based cohort studies using established core outcome sets in the first instance.
Role of nonneoplastic PVT in the natural history of patients with cirrhosis and first diagnosis of HCC
Authors: Senzolo Marco , Shalaby Sarah , Grasso Marco , Vitale Alessandro , Pizzirani Enrico , Barbiero Giulio , Zanetto Alberto , Feltracco Paolo , Simioni Paolo , Burra Patrizia , Cillo Umberto
Published: July 2023

Background and Aims:

HCC can increase the risk of nonneoplastic PVT in cirrhosis. However, the natural history of PVT and its prognostic role in HCC patients are unknown.

Approach and Results:

Consecutive HCC patients with cirrhosis undergoing laparoscopic ablation were retrospectively evaluated and followed up to 36 months. HCC and PVT characteristics and evolution were reviewed. PVT was categorized according to lumen occupancy (≤50%, >50% <100%, and = 100%) and extension to other veins. The evolution of thrombosis was considered at 1 year from diagnosis. Variables associated with the presence of PVT and evolution patterns were analyzed, as well as their impact on survival. In all, 750 patients were included, 88 of whom had PVT. On multivariate analysis, the occurrence of PVT at HCC diagnosis was associated with pretreatment total tumor volume (p < 0.001) and clinically significant portal hypertension (p = 0.005). During the follow-up, 46 de novo PVT occurred, 27/46 (58.7%) in the presence of a viable tumor. Among 115 PVT diagnosed in the presence of HCC, 83 had available radiological follow-up, and 22 were anticoagulated. The “complete/progressive” evolution pattern was associated with nonresponse to HCC treatment in non-anticoagulated patients. The presence of PVT was independently associated with lower overall survival, particularly when progressive or occlusive (p < 0.001). A higher competing risk of death emerged for “complete and progressive” PVT, both for HCC-related (p < 0.001) and non-HCC–related (p = 0.002) death.

Conclusions:

HCC represents an independent risk factor for the occurrence and progression of PVT in cirrhosis. Since progressive and occlusive PVT seems to be an independent factor associated with mortality, screening and prompt treatment of this complication should be considered.
Chemotherapy with or without selective internal radiation therapy for intrahepatic cholangiocarcinoma: Data from clinical trials
Authors: Edeline Julien , Bridgewater John , Campillo-Gimenez Boris , Neveu Estelle , Phelip Jean-Marc , Neuzillet Cindy , Boudjema Karim , Rolland Yan , Valle Juan W. , Garin Etienne , Malka David , Lamarca Angela
Published: July 2023

Backgound and Aims:

In advanced, liver-only intrahepatic cholangiocarcinoma (iCCA), selective internal radiation therapy (SIRT) has been suggested as promising in nonrandomized studies. We aimed to compare data from patients with advanced, liver-only iCCA treated in the first line in clinical trials with either chemotherapy alone or the combination with SIRT.

Approach and Results:

We collected individual patients’ data from the ABC-01, ABC-02, ABC-03, BINGO, AMEBICA, and MISPHEC prospective trials. Data from patients with liver-only iCCA treated in chemotherapy-only arms of the first 5 trials were compared with data from patients treated with SIRT and chemotherapy in MISPHEC. Emulated target trial paradigm and Inverse Probability of Treatment Weighting (IPTW methods) using the propensity score were used to minimize biases. We compared 41 patients treated with the combination with 73 patients treated with chemotherapy alone, the main analysis being in 43 patients treated with cisplatin-gemcitabine or gemcitabine-oxaliplatin. After weighting, overall survival was significantly higher in patients treated with SIRT: median 21.7 months (95% CI: 14.1; not reached) versus 15.9 months(95% CI: 9.8; 18.9), HR = 0.59 (95% CI: 0.34; 0.99), p = 0.049. Progression-free survival was significantly improved: median 14.3 months (95% CI: 7.8; not reached) versus 8.4 months (95% CI: 5.9; 12.1), HR = 0.52 (95% CI: 0.31; 0.89), p < 0.001. Results were confirmed in most sensitivity analyses.

Conclusions:

This analysis derived from prospective clinical trials suggests that SIRT combined with chemotherapy might improve outcomes over chemotherapy alone in patients with advanced, liver-only iCCA. Randomized controlled evidence is needed to confirm these findings.
Itaconate inhibits CD103+ TRM cells and alleviates hepatobiliary injury in mouse models of primary sclerosing cholangitis
Authors: Li Yikang , Li Bo , Xiao Xiao , Qian Qiwei , Wang Rui , Lyu Zhuwan , Chen Ruiling , Cui Nana , Ou Yiyan , Pu Xiting , Miao Qi , Wang Qixia , Lian Min , Gershwin M. Eric , Tang Ruqi , Ma Xiong , You Zhengrui
Published: July 2023

Background and Aims:

Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease characterized by the infiltration of intrahepatic tissue-resident memory CD8+ T cells (TRM). Itaconate has demonstrated therapeutic potential in modulating inflammation. An unmet need for PSC is the reduction of biliary inflammation, and we hypothesized that itaconate may directly modulate pathogenic TRM.

Approach and Results:

The numbers of intrahepatic CD103+ TRM were evaluated by immunofluorescence in PSC (n = 32), and the serum levels of itaconate in PSC (n = 64), primary biliary cholangitis (PBC) (n = 60), autoimmune hepatitis (AIH) (n = 49), and healthy controls (n = 109) were determined by LC-MS/MS. In addition, the frequencies and immunophenotypes of intrahepatic TRM using explants from PSC (n = 5) and healthy donors (n = 6) were quantitated by flow cytometry. The immunomodulatory properties of 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) on CD103+ TRM were studied in vitro. Finally, the therapeutic potential of itaconate was studied by the administration of 4-OI and deficiency of immune-responsive gene 1 (encodes the aconitate decarboxylase producing itaconate) in murine models of PSC. Intrahepatic CD103+ TRM was significantly expanded in PSC and was positively correlated with disease severity. Serum itaconate levels decreased in PSC. Importantly, 4-OI inhibited the induction and effector functions of CD103+ TRM in vitro. Mechanistically, 4-OI blocked DNA demethylation of RUNX3 in CD8+T cells. Moreover, 4-OI reduced intrahepatic CD103+ TRM and ameliorated liver injury in murine models of PSC.

Conclusions:

Itaconate exerted immunomodulatory activity on CD103+ TRM in both in vitro and murine PSC models. Our study suggests that targeting pathogenic CD103+ TRM with itaconate has therapeutic potential in PSC.
Novel Manifestation of Corneal Dystrophy After Keratorefractive Surgery
Authors: Yeh Tsai-Chu , Hsu Chih-Chien , Lu Yung-Hsiu , Chen Yun-Ru , Niu Dau-Ming , Lin Pei-Yu
Published: July 2023

Purpose:

This study aimed to report cases of bilateral corneal Bowman layer deposits in 4 patients with a history of keratorefractive surgery. To our knowledge, this condition has not previously been reported and should be distinguished from granular corneal dystrophy type 2 and other corneal dystrophies.

Methods:

We reviewed all available medical records that were collected between January 2010 and December 2021 at a tertiary referral center and performed whole-exome sequencing to provide diagnostic information.

Results:

Four patients exhibited similar bilateral corneal deposits that were observed more than 10 years after keratorefractive surgery. The patients' ages ranged from 36 to 53 years; 3 of the 4 patients were female. Three patients received laser in situ keratomileusis surgery, and 1 received radial keratotomy. All 4 patients denied having a family history of ocular diseases and reported an uneventful postoperative course. On examination, the best-corrected visual acuity ranged from 6/10 to 6/6 in all 4 patients. Slit-lamp examination revealed bilateral superficial corneal deposits involving the central cornea, and anterior segment optical coherence tomography revealed hyperreflective deposits located in the Bowman layer. Such unique manifestations suggested corneal dystrophy; thus, whole-exome sequencing was performed on all 4 patients. Only 1 patient exhibited a missense mutation in TGFBI. We further analyzed common de novo mutations to explore possible candidate genes associated with this presentation.

Conclusions:

We report a rare entity of presumed corneal dystrophy with deposits located in the Bowman layer in 4 patients who had received keratorefractive surgery. Clarifying the underlying pathophysiology and genetic predisposition of this disease may aid in diagnosing and preventing potential complications after keratorefractive surgery.
Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV
Authors: Chabala Chishala , Turkova Anna , Kapasa Monica , LeBeau Kristen , Tembo Chimuka H. , Zimba Kevin , Weisner Lubbe , Zyambo Khozya , Choo Louise , Chungu Chalilwe , Lungu Joyce , Mulenga Veronica , Crook Angela , Gibb Diana , McIlleron Helen ,   on behalf of the SHINE trial team
Published: July 2023

Background:

Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment.

Methods:

Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment.

Results:

Of 20 children enrolled; 15, 1–7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve0–24 55.32 mg/h/L [0.30–398.7 mg/h/L]; Cmax 3.04 mg/L [0.03–18.6 mg/L]; C8hr 0.90 mg/L [0.01–13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve24 121.63 mg/h/L [2.56–487.3 mg/h/L]; Cmax 9.45 mg/L [0.39–26.4 mg/L]; C12hr 3.03 mg/L [0.01–17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L.

Conclusions:

Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation.
Work-Life Balance and Mental Health Outcomes for Generation Z in Germany
Authors: Adedeji Adekunle , Langel Carlotta , Feick Amelie , Borges Greibaum Martha-Sofia , Rahimi Maryam , Hanft-Robert Saskia
Published: July 2023

Objective

Mental health can be negatively affected if work and private life demands are not balanced. This study proposes exploring work-life balance (WLB) as a predictor of Generation Z's mental health outcomes.

Methods

A cross-sectional online study was conducted to collect data on mental health outcomes and WLB from a sample of Generation Z (N = 134). Three regression models were calculated to examine the predictive effect of WLB on stress, anxiety, and depressive symptoms.

Results

The results show a strong statistically significant association between all three mental health outcomes. The regression model suggests work-life balance as a predictor of stress (β =.−0.404 P = 0.001, R2 = 0.16) and anxiety (β = .−256 P = 0.001, R2 = 0.06).

Conclusion

WLB must be considered a significant factor in mental health problems among Generation Z.
Transcanal Endoscopic Management of Middle Ear Paragangliomas
Authors: Surmelioglu Ozgur , Bajin Munir Demir , Kaya Isa , Okuyucu Semsettin , Ozturk Kayhan , Orhan Kadir Serkan , Karlıdag Turgut , Ardıc Fazil Necdet , Ozdek Ali , Yorgancılar Ediz , Dagkiran Muhammed , Celik Mehmet
Published: July 2023

Objective

To evaluate the clinical and audiological outcomes of transcanal endoscopic resection of middle ear paragangliomas.

Study Design

Retrospective multicenter study.

Setting

Tertiary referral center and private otology clinic.

Patients

Patients who underwent transcanal endoscopic surgery between January 2015 and September 2020.

Intervention(s)

Transcanal endocope-assisted resection of middle ear paragangliomas.

Main Outcome Measure(s)

Demographic data.

Results

Twenty-three patients (2 men, 21 women) with a mean (standard deviation [SD]) age of 50.5 (11.8) years and stage 1 or 2 disease were included in the study. The mean follow-up time was 2.7 years (range, 1–5 yr). Preoperatively, the mean (SD) air-conduction threshold was 33.8 (17.9) dB, and the mean (SD) air-bone gap was 13.1 (13.9) dB. Postoperatively, the mean (SD) air-conduction threshold was 25.7 (10.2) dB, the mean (SD) air-bone gap was 6.3 (6.1) dB. The mean (SD) hospital stay was 27.7 (9.9) hours. No tumor regrowth was detected on magnetic resonance imaging during postoperative follow-up.

Conclusions

Endoscopic transcanal tumor resection is effective and feasible in the treatment of stage 1 and 2 tumors and is associated with short operative time, low risk of perioperative and postoperative complications, and rapid discharge.
Round-Window Vibroplasty: Systematic Review and Meta-Analysis of Audiological Effectiveness With Different Round-Window Coupling Techniques
Authors: Hundertpfund Julia , Dejaco Thomas , Meyer Jens Eduard , Óvári Attila
Published: July 2023

Objective

Active middle ear implants can be directly coupled to the round-window (RW) membrane via RW Vibroplasty. The objectives of this systematic review were to summarize data on different RW coupling techniques and to investigate their effect on audiological and safety outcomes using meta-analyses.

Databases reviewed

PubMed (MEDLINE), Cochrane Library, and Embase (DIMDI).

Methods

All publications reporting on audiological outcomes in human patients after RW Vibroplasty were included. Two independent reviewers carried out screening and data extraction. Meta-analyses and meta-regression were used to evaluate the potential effects of surgical and demographic parameters on primary audiological outcomes. Adverse events were extracted and tabulated for qualitative analysis.

Results

Fourteen different combinations of surgical coupling parameters were identified in 61 included publications. Overall, data from 23 publications could be used for meta-analyses. Significantly better aided sound-field thresholds were reported for RW Vibroplasty performed without a dedicated coupler and using fascia as interponate, compared with RW Vibroplasty with an RW coupler or without an interponate. These effects were not found in other outcomes (i.e., functional gain, word recognition score). Reporting of adverse events was relatively heterogeneous, with 32 explicit mentions of revision surgery after the loss of coupling efficacy.

Conclusion

There are numerous publications investigating the effectiveness of coupling active middle ear implants to the RW membrane. However, studies are typically undersampled and of low evidence level. Using meta-analyses, weighted means, and qualitative analyses enabled a summary of the existing literature on audiological and safety outcomes after RW Vibroplasty. Individual selection of the most appropriate coupling modality with standardized intraoperative measurement and careful patient follow-up may be considered key factors for achieving effective RW coupling.
Predictors of Career Placement Among American Neurotology Society Fellowship Graduates
Authors: Choe Erica , Hakimi Amir A. , Hoa Michael
Published: July 2023

Abstract and Objective

To identify predictors of practice type and location after neurotology fellowship based on demographics and educational history.

Study Design

Cross-sectional analysis.

Setting

Conference programs from the American Neurotology Society Spring Meeting from 2016 to 2022.

Main Outcome Measure

Percentage of neurotologists who pursued academic careers.

Results

A total of 114 neurotology fellows were identified. Of the 98 individuals included in final analysis, 64 (65%) pursued academic careers. Fellows most likely to enter academic practice trained at a residency program ranked in the top 50% based on Doximity residency rankings by reputation (74 versus 45%, p < 0.01) or graduated from a residency program with a neurotology fellowship (82 versus 56%, p < 0.01). Graduates from fellowship programs in the Northeast were most likely to enter academic careers (83%). Fifty percent of neurotologists practiced in the same region as their residency training, and 48% practiced the same region as their fellowship. The region with the highest number of practicing neurotology graduates was the South (47%).

Conclusion

Residency program ranking and residency institutions with neurotology fellowships were the leading predictors of academic career placement in the field of neurotology. Many neurotologists tend to stay in a similar geographical location to where they underwent medical training.
Speed of Information Processing and Verbal Working Memory in Children and Adolescents With Cochlear Implants
Authors: Herran Reid M. , Montgomery Caitlin J. , Henning Shirley C. , Herbert Carolyn J. , Ditmars Allison M. , Yates Catherine J. , Pisoni David B. , Kronenberger William G.
Published: July 2023

Background

Verbal working memory delays are found in many deaf children with cochlear implants compared with normal-hearing peers, but the factors contributing to these delays are not well understood. This study investigated differences between cochlear implant users and normal-hearing peers in memory scanning speed during a challenging verbal working memory task. To better understand variability in verbal working memory capacity within each sample, associations between memory scanning speed, speech recognition, and language were also investigated.

Methods

Twenty-five prelingually deaf, early implanted children (age, 8–17 yr) with cochlear implants and 25 normal-hearing peers completed the Wechsler Intelligence Scale for Children, Fifth Edition, Letter-Number Sequencing (LNS) working memory task. Timing measures were made for response latency and average pause duration between letters/numbers recalled during the task. Participants also completed measures of speech recognition, vocabulary, and language comprehension.

Results

Children with cochlear implants had longer pause durations than normal-hearing peers during three-span LNS sequences, but the groups did not differ in response latencies or in pause durations during two-span LNS sequences. In the sample of cochlear implant users, poorer speech recognition was correlated with longer pause durations during two-span sequences, whereas poorer vocabulary and weaker language comprehension were correlated with longer response latencies during two-span sequences. Response latencies and pause durations were unrelated to language in the normal-hearing sample.

Conclusion

Children with cochlear implants have slower verbal working memory scanning speed than children with normal hearing. More robust phonological-lexical representations of language in memory may facilitate faster memory scanning speed and better working memory in cochlear implant users.
Health Insurance Coverage of Cochlear Implantation in Single-Sided Deafness and Asymmetric Hearing Loss
Authors: Sorkin Donna L. , Adunka Oliver F. , Westin Nichole
Published: July 2023

Objective

There is increasing interest in providing cochlear implants (CIs) in single-sided deafness (SSD) or asymmetric hearing loss (AHL). CI clinics have experienced a range of outcomes when seeking insurance coverage for patients. The study explored the extent to which CI clinics were able to secure insurance coverage and whether there were differences in successfully gaining such coverage.

Study Design

A SurveyMonkey questionnaire was used to collect data from US CI clinicians. Respondents were from all regions of the United States and represented a diversity of clinic types including hospitals, university-based clinics, private clinics, and schools. Data were collected during August–October 2021 from 105 respondents regarding their clinic's experience in gaining health insurance coverage for pediatric and adult patients who had SSD or AHL. Strategies that had been used for gaining coverage after an initial denial were explored. Interviews were conducted with some respondents to gain additional insights beyond the survey.

Results

There was a substantial increase in the number of SSD operations conducted after 2019, the year when the Food and Drug Administration (FDA) manufacturer criteria expanded to include CI in SSD and AHL. Respondents were grouped into four categories based on volume of SSD operations before 2019 (≤10, 11–29, 30–49, and ≥50). The number of SSD operations after 2019 went up in all categories except for the 10 or less category, which declined by 43%. A minority of respondents indicated that they were able to obtain SSD insurance coverage infrequently (5%) or almost never (8%). Peer-to-peer review was the most successful approach to overturning an initial denial. Many clinics note that they are nearly always declined for SSD coverage on the first submission and must appeal.

Conclusions

There is variability in CI coverage for SSD and AHL. Some health insurance coverage is available for patients of all ages, although some clinics note more difficulty gaining coverage for children younger than 5 years because of the FDA criteria. Clinicians are most successful at gaining coverage after an initial denial with peer-to-peer review, although the process is time-consuming and delays surgery. Efforts to expand access to CIs in SSD for children and adults who may benefit might best be addressed by reflecting on what was done to expand insurance coverage in bilateral deafness—a process that depended on relevant clinical research; research presented to the FDA for guidelines change; information sharing with the general public and constituencies in the hearing loss field including professionals, parent, and consumer organizations; and ongoing advocacy for change with insurers. To date, outcomes research in young children with CI in SSD is limited. Until such research is conducted and published, insurers will continue to argue that other rehabilitative options are approved and available.
Extracorporal Membrane Oxygenation in Nonintubated Patients (Awake ECMO) With COVID-19 Adult Respiratory Distress Syndrome: The Israeli Experience
Authors: Galante Ori , Hasidim Ariel , Almog Yaniv , Cohen Amir , Makhoul Maged , Soroksky Arie , Zikri-Ditch Meital , Fink Daniel , Ilgiyaev Eduard
Published: July 2023

In this retrospective multicenter observational study, we describe the Israeli experience with veno-venous extracorporeal membrane oxygenation (VV ECMO) for the treatment of COVID-19-induced severe adult respiratory distress syndrome (ARDS), in which ECMO cannulation was done while the patients were awake and spontaneously breathing without endotracheal tube, namely “awake ECMO.” We enrolled all adult patients with severe ARDS due to COVID-19, treated with VV ECMO between March 1, 2020, and November 30, 2021, in which cannulation was done while the patient was awake and spontaneously breathing. During the study period, 365 COVID-19 ARDS patients were treated with VV ECMO. Of these, 25 (6.8%) were treated as awake ECMO. The patient’s mean age was 52 years, and 80% were male. Nine of the 25 patients (36%) remained awake throughout their intensive care unit stay and were not sedated and mechanically ventilated at all. Sixteen (64%) were eventually intubated while being on ECMO. Six months survival was 76%. Median mechanical ventilation-free days on ECMO was 8 (interquartile range 5–12) days.

This hypothesis-generating study suggests that treating COVID-19 ARDS patients with VV ECMO without sedation and mechanical ventilation is feasible, yet, additional research will be required in order to determine if this modality offers a survival benefit and to identify who are the patients most likely to benefit from it.
Botox (onabotulinumtoxinA) mechanism of action
Authors: Brin Mitchell F. , Burstein Rami
Published: July 2023

Studies in the 1920s found that botulinum neurotoxin type A (BoNT/A) inhibited the activity of motor and parasympathetic nerve endings, confirmed several decades later to be due to decreased acetylcholine release. The 1970s were marked by studies of cellular mechanisms aided by use of neutralizing antibodies as pharmacologic tools: BoNT/A disappeared from accessibility to neutralizing antibodies within minutes, although it took several hours for onset of muscle weakness. The multi-step mechanism was experimentally confirmed and is now recognized to consist broadly of binding to nerve terminals, internalization, and lysis or cleavage of a protein (SNAP-25: synaptosomal associated protein-25 kDa) that is part of the SNARE (Soluble NSF Attachment protein REceptor) complex needed for synaptic vesicle docking and fusion. Clinical use of the BoNT/A product onabotulinumtoxinA was based on its ability to reduce muscle contractions via inhibition of acetylcholine from motor terminals. Sensory mechanisms of onabotulinumtoxinA have now been identified, supporting its successful treatment of chronic migraine and urgency in overactive bladder. Exploration into migraine mechanisms led to anatomical studies documenting pain fibers that send axons through sutures of the skull to outside the head—a potential route by which extracranial injections could affect intracranial processes. Several clinical studies have also identified benefits of onabotulinumtoxinA in major depression, which have been attributed to central responses induced by feedback from facial muscle and skin movement. Overall, the history of BoNT/A is distinguished by basic science studies that stimulated clinical use and, conversely, clinical observations that spurred basic research into novel mechanisms of action.
Autoimmune liver diseases and diabetes
Authors: Jensen Anne-Sofie H. , Ytting Henriette , Winther-Sørensen Marie , Burisch Johan , Bergquist Annika , Gluud Lise Lotte , Wewer Albrechtsen Nicolai J.
Published: July 2023

Autoimmune liver diseases include autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. They are chronic, heterogenous diseases affecting the liver which is a key metabolic organ that ensures glucose homeostasis. It is well known that patients with other chronic liver diseases such as cirrhosis and nonalcoholic fatty liver disease (NAFLD) display glucose disturbances like insulin resistance and have an increased risk of diabetes. Previous evidence on glucose disturbances in patients with autoimmune liver disease is scarce but does point towards a potentially increased risk of type 1 diabetes and type 2 diabetes. The underlying mechanisms are unknown but may reflect genetic predisposition, concurrent NAFLD and or cirrhosis development, and treatment (steroid) related impairment of glucose homeostasis. Therefore, increased awareness and surveillance of diabetes development in patients with autoimmune liver disease may be important. Overall, detection and treatment of diabetes generally follow the usual diabetes guidelines; however, in patients with advanced liver cirrhosis, HbA1c may not be a reliable marker of average glucose levels, and treatment with insulin is generally recommended. In addition, it has recently been suggested that sodium–glucose cotransporter 2 inhibitors may be beneficial in treating refractory ascites. Further research on diabetes risk in autoimmune liver disease is warranted.
A meta-analysis of microbiome therapies for hepatic encephalopathy
Authors: Gao Jie , Nie Rui , Chang Hong , Yang Wei , Ren Qian
Published: July 2023

Microbiome therapies may be reported to be effective in hepatic encephalopathy (HE). We thus did a meta-analysis of randomized controlled trials to assess the effect of microbiome therapies for HE. We systematically searched PubMed, Web of Science, EMBASE, and Cochrane Library for randomized controlled trials that compared the different treatments for HE including probiotics, symbiotics, and fecal microbiota transplant (FMT). Meta-analysis was performed to calculate pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Twenty-one studies met our inclusion criteria (N = 1746 participants). Probiotics, synbiotics and FMT significantly reversed minimal HE (MHE) (OR: 0.41, 95% CI: 0.19–0.90, P = 0.03), reduced overt HE (OHE) development (OR, 0.41; 95% CI: 0.28–0.61 P < 0.00001)and the frequency of serious adverse events(SAEs) (OR:0.14, 95% CI: 0.04–0.47, P = 0.001), meanwhile decreased ammonia levels (WMD: −9.26, 95% CI: −16.92 to −1.61; P = 0.02), NCT level (MD = −4.41, 95% CI: −0.87 to −0.22, P = 0.04) and hospitalization rates (OR, 0.38; 95% CI: 0.19–0.79, P = 0.009) compared with placebo/no treatment. Finally, we conclude that microbiome therapies were more effective in improving MHE and preventing progression to OHE, reducing the frequency of SAEs, and decreasing ammonia levels, NCT level, and hospitalization rates when compared to placebo/no treatment.
Gastric cancer risk in the elderly is associated with omeprazole use and inversely associated with aspirin use
Authors: Gingold-Belfer Rachel , Issa Nidal , Boltin Doron , Beloosesky Yichayaou , Koren-Morag Nira , Meyerovitch Joseph , Sharon Eran , Peleg Noam , Schmilovitz-Weiss Hemda
Published: July 2023

Background

The association between long-term omeprazole use and gastric cancer (GC) risk is controversial. The aim of this study was to investigate the incidence of GC in elderly community-dwelling omeprazole chronic users with/without aspirin compared to non-users.

Methods

The registry of a large health management organization was searched for all community-dwelling members aged ≥65 years from January 2002 to December 2016. Data on demographics, background parameters, and chronic omeprazole and aspirin use (>11 prescriptions/year) were retrieved. Those diagnosed with new-onset GC during the study period (from January 2003) were identified.

Results

Of 51 405 subjects who met the inclusion criteria, 197 were diagnosed with GC during a mean follow-up period of 8.74 ± 4.16 years. This group accounted for 0.7% of PPI chronic users (72/11 008) and 0.3% (125/40 397) of nonusers (P < 0.001). GC risk was directly associated with omeprazole chronic use [hazard ratio (HR) 2.03, 95% confidence interval (CI): 1.51–2.73, P < 0.001] and inversely associated with aspirin chronic use (HR 0.55, 95% CI: 0.40–0.75, P < 0.001). Each year of omeprazole use increased GC risk by 9%, and each year of aspirin use decreased GC risk by 10% among omeprazole chronic users. The lowest rate of GC was found in omeprazole nonusers/ aspirin chronic users, and the highest, in omeprazole chronic users/aspirin nonusers.

Conclusion

Higher GC rate was associated with omeprazole chronic use and inversely associated with aspirin chronic use relative to omeprazole nonuse in community-dwelling elderly.
Meditation—A Slippery Slope for Psychosis
Authors: Yadav Jagriti , Bhardwaj Akansha , Jangid Purushottam , Singh Priti , Gupta Rajiv
Published: July 2023

The practice of meditation has been traditionally viewed as a self-regulatory approach that aids in psychological well-being. Over the last decade, mindfulness-based meditation has gained a separate therapeutic significance in various mental health conditions. There has also been considerable understanding of the adverse effects of meditation over the years. Despite this, there is still underreporting of the altered behavioral presentations arising possibly because of intensive and unguided meditation practices. We present two cases of meditation-related psychosis with different clinical presentations. The write-up highlights the need for tailoring the meditation practices after evaluation of mental state of the individuals and early detection of “at-risk” mental states. There should be regular screening of emergence of any unwanted effects during the course of meditation and the guides should be able to detect the early warning signs of psychosis.
Pornography Consumption and Cognitive-Affective Distress
Authors: Privara Michal , Bob Petr
Published: July 2023

According to recent studies, the growing consumption of Internet pornography mainly in male population becomes an increasing problem, which is closely linked to compulsive sexual behavior. Some findings also suggest that Internet pornography consumption might represent a defense mechanism against excessive stress, which enables to cope with stressful events, helps in mood regulation, and decreases depression and anxiety. Users of online pornography involved in these activities also reported that their self-exposition to pornographic material may create guilty feelings and internal conflict in themselves with respect to their own “involuntary” sexual behavior, which suggest that psychosocial stress and possibly traumatic experiences may play a significant role in Internet pornography addiction. Taken together, these findings show that stressful experiences, anxiety, and depression are strongly related to pornography consumption. In addition, conflicting emotional experiences as well as identity problems significantly increase vulnerability to addictive sexual behavior and pornography consumption.
Evaluation of the Levels of Low-dose Topical Atropine (0.01%) in Aqueous and Vitreous Humor in Human Eyes
Authors: Kumar Prakash , Saxena Rohit , Dhiman Rebika , Phuljhele Swati , Kumar Vinod , Chawla Rohan , Velpandian Thirumurthy
Published: July 2023

SIGNIFICANCE

This is the first human study that confirmed penetration of 0.01% topical atropine in aqueous and vitreous humor in live human eyes. This supports the possible mode of action of atropine via posterior ocular structures. This knowledge will help improve the outcomes in myopia management.

PURPOSE

The purpose of this study was to evaluate penetration of low-dose atropine 0.01% in aqueous and vitreous humor.

METHODS

In this cross-sectional interventional pilot study, 48 cataract cases were divided into four groups (12 each), and 30 epiretinal membrane/macular hole cases were divided into three groups (10 each). One drop of 0.01% atropine was put in the eye to be operated. Aqueous humor samples were taken from patients undergoing cataract surgery at 60 ± 15 minutes in group 1, 120 ± 15 minutes in group 2, 240 ± 15 minutes in group 3, and 360 ± 15 minutes in group 4. Vitreous humor samples were taken from patients undergoing vitreoretinal surgery for epiretinal membrane/macular hole at 120 ± 15 minutes in group 1, 240 ± 15 minutes in group 2, and 360 ± 15 minutes in group 3. The assay of atropine was performed using liquid chromatography–mass spectrometry.

RESULTS

Median concentrations of atropine in aqueous samples were 1.33 ng/mL (min-max, 0.6 to 6.46 ng/mL; interquartile range [IQR], 3.05 ng/mL) at 60 minutes, 2.60 ng/mL (min-max, 0.63 to 4.62 ng/mL; IQR, 1.97 ng/mL) at 120 minutes, 1.615 ng/mL (min-max, 0.1 to 3.74 ng/mL; IQR, 1.62 ng/mL) at 240 minutes, and 1.46 ng/mL (min-max, 0.47 to 2.80 ng/mL; IQR, 1.73 ng/mL) at 360 minutes, and those in vitreous samples were 0.102 ng/mL (min-max, 0 to 0.369 ng/mL; IQR, 0.366 ng/mL) at 120 minutes, 0.1715 ng/mL (min-max, 0 to 0.795 ng/mL; IQR, 0.271 ng/mL) at 240 minutes, and 0.2495 ng/mL (min-max, 0 to 0.569 ng/mL; IQR, 0.402 ng/mL) at 360 minutes, respectively.

CONCLUSIONS

Measurable concentration of low-dose topical atropine (0.01%) was noted in aqueous and vitreous humor after instillation of a single drop of low-dose atropine. Muscarinic receptors located in the posterior segment such as the choroid and retina could be the possible site of action of low-dose atropine in myopia.
Digital Papillary Adenocarcinoma in Nonacral Skin
Authors: Kervarrec Thibault , Imbeaud Sandrine , Veyer David , Pere Helene , Puech Julien , Pekár-Lukacs Agnes , Markiewicz Dorota , Coutts Michael , Tallet Anne , Collin Christine , Berthon Patricia , Bravo Ignacio G. , Seris Alice , Jouary Thomas , Macagno Nicolas , Touzé Antoine , Cribier Bernard , Battistella Maxime , Calonje Eduardo
Published: July 2023

Digital papillary adenocarcinoma (DPA) is a rare sweat gland neoplasm that has exceptionally been reported outside acral locations. Recently, human papillomavirus 42 was identified as the main oncogenic driver of DPA. Herein, we report 5 tumors arising in extra-acral locations predominantly in the female anogenital skin. Four patients were female and 1 patient was male. The mean age at the diagnosis time was 65 years (range: 55 to 82 y). Tumors were located on the vulva (n=3), perianal area (n=1), and forearm (n=1). Histologically, all tumors were lobular and mainly solid and composed of sheets of cells with rare focal papillae and frequent glandular structures in a “back-to-back” pattern and lined by atypical basophilic cells. Immunohistochemistry showed diffuse positivity for SOX10. Epithelial membrane antigen and carcinoembryonic antigen highlighted the luminal cells and staining for p63 and p40 revealed a consistent and continuous myoepithelial component around glandular structures. Follow-up was available in 3 cases (mean duration: 12 mo [range: 8 to 16 mo]). One patient developed local recurrence and 1 experienced regional lymph node metastases. HPV Capture Next-generation sequencing revealed the presence of the HPV42 genome in all samples. Viral reads distributions were compatible in the 5 cases with an episomal nature of the viral genome, with a recurrent deletion in the E1 and/or E2 open reading frames. In conclusion, this study demonstrates that digital DPA may rarely present in nonacral locations mainly in the female anogenital area, usually with a more solid pattern as compared with those cases presenting on the digits and it is also associated with HPV42.
Racial and Educational Disparities in Cumulative Exposure to Hardships of the 2008 Great Recession and Inflammation
Authors: Kirsch Julie A. , Coe Christopher , Ryff Carol D.
Published: July 2023

Objective

This cross-sectional analysis examined self-reported economic hardships of the 2008 Great Recession, race/ethnicity, educational attainment, and psychological well-being (PWB) as predictors of systemic inflammatory physiology at midlife. We also tested for differential vulnerability in the relationship between recession hardship and inflammatory physiology by race/ethnicity, education, and PWB.

Methods

Adults from the Midlife in the United States Refresher sample completed a survey and biomedical assessments after the recession (n = 592 non-Hispanic White respondents, n = 158 Black/African American respondents, n = 108 respondents with other race/ethnicity). Cumulative recession hardship was the sum of financial, housing, and employment-related events. Outcomes included circulating levels of interleukin 6 and C-reactive protein. General linear regression models tested main effects interactions between primary predictor variables.

Results

Educational attainment was inversely associated with recession hardships (b = −0.18, 95% confidence interval = −0.26 to −0.11, p < .001). Black/African American respondents reported more recession hardships than White respondents (b = 1.17, 95% confidence interval = 0.67 to 1.68, p < .001). More recession hardships predicted higher levels of interleukin 6 (b = 0.06, p < .001) and C-reactive protein (b = 0.04, p = .004). Analyses did not support race/ethnicity, education, and PWB as moderators of the association between recession hardship and inflammatory markers.

Conclusions

Race/ethnicity and education independently predicted disparities in cumulative recession hardship exposure. Recession hardship predicted higher blood levels of inflammatory proteins associated with long-term health. The lack of findings for differential vulnerability in the relationship between recession hardship and inflammatory markers by race/ethnicity, education, or PWB was possibly due to the limited sample size.
Postpartum Insomnia and Poor Sleep Quality Are Longitudinally Predictive of Postpartum Mood Symptoms
Authors: Okun Michele L. , Lac Andrew
Published: July 2023

Objective

Insomnia and poor sleep quality are frequently reported by perinatal women. Both are noted to increase the risk of postpartum depression, with less known about their association with postpartum anxiety. This study sought to assess whether perinatal sleep disturbances predicted depression and anxiety symptoms across each month of the first 6 months postpartum in women with a history of depression.

Methods

Pregnant women without active depression at enrollment (N = 159), 18 to 45 years of age, were recruited. In late pregnancy and for up to 6 months postpartum, women completed monthly online questionnaires including the Insomnia Symptom Questionnaire, Pittsburgh Sleep Quality Index, Edinburgh Postnatal Depression Scale, and Generalized Anxiety Disorder-7. Repeated-measures multilevel models were used to predict depression and anxiety across the postpartum.

Results

The prevalence of insomnia was 20.4%, and the prevalence of poor sleep quality was 67.8% across the first 6 months postpartum. Postpartum insomnia and poor sleep quality at the between-subject and within-subject levels tended to uniquely predict greater depressive and anxiety symptoms, even after controlling for demographic characteristics, prenatal insomnia, and prenatal poor sleep quality.

Conclusions

Most of the women in our sample had sleep disturbances across the perinatal period. Consistent with the extant literature, postpartum insomnia and poor sleep quality, but not prenatal measures of sleep, longitudinally predicted greater postpartum depression and anxiety symptoms. The chronic sleep deprivation of insomnia and the subjective experience of poor sleep quality are uniquely relevant risks of postpartum mood disorders. Evaluation and mitigation of perinatal sleep disturbance are ideal opportunities to reduce postpartum mood disorders and subsequent health outcomes.