bluuebunny/crossref_metadata_2025 huggingface dataset:
I SISTEMI PARTITICI REGIONALI IN ITALIA DALLA PRIMA ALLA SECONDA REPUBBLICA
Authors: Mazzoleni Martino
Published: January 2022

Introduzione

Negli scorsi decenni sono state proposte nella letteratura politologica diverse descrizioni e classificazioni dei sistemi di partito, sulla base del loro formato e della loro meccanica interna. L'argomento della differenziazione territoriale dei sistemi partitici, però, è stato piuttosto trascurato nello studio di questa materia. E tuttavia «nei grandi stati vi sono in realtà relativamente pochi fenomeni politici che la popolazione sperimenta in maniera omogenea», e i dati nazionali sovente rappresentano solo delle «medie di esperienze soggiacenti abbastanza differenti» (Dunleavy e Margetts 1994). Questo saggio mira a sviluppare tale argomento con riferimento ad un caso specifico, la realtà politica italiana dal 1970 ad oggi. Si evidenzierà come ed in quale misura un sistema partitico nazionale possa comprendere vari sub-sistemi, costituiti dagli stessi soggetti ma al contempo diversificati in più aspetti.
Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA
Authors: Facon Thierry , Cook Gordon , Usmani Saad Z. , Hulin Cyrille , Kumar Shaji , Plesner Torben , Touzeau Cyrille , Bahlis Nizar J. , Basu Supratik , Nahi Hareth , Goldschmidt Hartmut , Quach Hang , Mohty Mohamad , Venner Christopher P. , Weisel Katja , Raje Noopur , Hebraud Benjamin , Belhadj-Merzoug Karim , Benboubker Lotfi , Decaux Olivier , Manier Salomon , Caillot Denis , Ukropec Jon , Pei Huiling , Van Rampelbergh Rian , Uhlar Clarissa M. , Kobos Rachel , Zweegman Sonja
Published: January 2022

In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10–5) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.
Drastic transitions of excited state and coupling regime in all-inorganic perovskite microcavities characterized by exciton/plasmon hybrid natures
Authors: Enomoto Shuki , Tagami Tomoya , Ueda Yusuke , Moriyama Yuta , Fujiwara Kentaro , Takahashi Shun , Yamashita Kenichi
Published: January 2022

Lead-halide perovskites are highly promising for various optoelectronic applications, including laser devices. However, fundamental photophysics explaining the coherent-light emission from this material system is so intricate and often the subject of debate. Here, we systematically investigate photoluminescence properties of all-inorganic perovskite microcavity at room temperature and discuss the excited state and the light–matter coupling regime depending on excitation density. Angle-resolved photoluminescence clearly exhibits that the microcavity system shows a transition from weak coupling regime to strong coupling regime, revealing the increase in correlated electron–hole pairs. With pumping fluence above the threshold, the photoluminescence signal shows a lasing behavior with bosonic condensation characteristics, accompanied by long-range phase coherence. The excitation density required for the lasing behavior, however, is found to exceed the Mott density, excluding the exciton as the excited state. These results demonstrate that the polaritonic Bardeen–Cooper–Schrieffer state originates the strong coupling formation and the lasing behavior.
Experimental investigations and model-based optimization of CZZ/H-FER 20 bed compositions for the direct synthesis of DME from CO2-rich syngas
Authors: Wild Stefan , Lacerda de Oliveira Campos Bruno , Zevaco Thomas A. , Guse David , Kind Matthias , Pitter Stephan , Herrera Delgado Karla , Sauer Jörg
Published: January 2022

Kinetic investigations and model-based optimization of CuO/ZnO/ZrO2 : H-FER 20 catalytic systems for direct DME synthesis from CO2-rich syngas.
Ten-year trends in mortality and complications following catheter ablation of atrial fibrillation
Authors: Ngo Linh , Ali Anna , Ganesan Anand , Woodman Richard , Adams Robert , Ranasinghe Isuru
Published: January 2022

Aims

Recent US studies report rising rates of mortality and in-hospital complications following catheter ablation of atrial fibrillation (AF), but whether this is a global phenomenon is uncertain. The aim of this study was to examine trends in 30-day mortality and complications following AF ablation in Australia and New Zealand (ANZ) from 2008 to 2017.

Methods and results

We identified 37 243 AF (mean age 62.4 ± 11.5 years, 29.6% females, 94.5% elective procedures) ablations using national hospitalization data. The primary outcome was occurrence of any complication, including all-cause mortality, within 30 days of discharge. Trends were evaluated using logistic regression adjusting for changes in patient characteristics. The annual number of ablations increased from 1359 (2008) to 5115 (2017). Patients’ age and rates of heart failure (9.8–10.6%), diabetes (6.8–12.4%), and chronic kidney disease (2.2–4.1%) also increased over time. From 2008 to 2017, the overall rate of complications declined from 7.51% to 5.04% [adjusted odds ratio (aOR) 0.96 (95% confidence interval, CI, 0.94–0.97)/year]. Rates of pericardial effusion [1.69–0.70%, aOR 0.93 (0.89–0.97)], bleeding [4.49–2.74%, aOR 0.94 (0.92–0.96)], and vascular injury [0.52–0.16%, aOR 0.91 (0.85–0.98)] declined, but rates of acute kidney injury [0.15–0.68%, aOR 1.16 (1.08–1.25)] and infection [0.15–0.57%, aOR 1.07 (1.01–1.14)] increased over time. The overall 30-day mortality rate was low (0.11%) and unchanged [0.00–0.16%, aOR 0.99 (0.88–1.11)].

Conclusion

Despite a five-fold increase in AF ablations and the rising risk profile of patients, complications following AF ablation declined by 30% from 2008 to 2017 in ANZ. Procedure-related death was uncommon and occurred in less than 1 in 850 patients.
Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate
Authors: Chang Cheng-Chen , Chen Po See , Lin Jhih-Rong , Chen Yi-An , Liu Chin-San , Lin Ta-Tsung , Chang Hui Hua
Published: January 2022

Background

Bipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients.

Methods

Sixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale.

Results

BD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS.

Conclusions

The study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.
Aesthetics of the Narrative Climax in Contemporary TV Serials
Authors: Pérez Héctor J
Published: January 2022

This article draws on concepts from cognitive psychology to explore the significance of the narrative climax, focusing on the final climax of the series The Americans as a case study. Two aspects of the aesthetic experience are considered: the special intensity that climaxes elicit, and the diversity of the cognitive content they generate, which can include both aesthetic and non-aesthetic properties. The climax is experienced in a state of absorption triggered by a set of strategies of temporal prolongation related to the main suspenseful moments and plotlines, to character engagement, and to the multiplot structure, involving the content of the narrative itself (narrative absorption) and the aesthetic qualities that define it (artifact absorption). The source of this absorption during the climax lies in the interplay between emotion and cognition in a temporal process that may last for a whole series. To demonstrate this idea, this study identifies key narrative comprehension processes, drawing on the explanatory potential of mental model theory to clarify the importance of memory and interrelated inferential processes. The aim of this research is to contribute to explanations of the role of the climax in serialized television and other artistic works.
Postoperative hypofractionated–accelerated radiotherapy (HypoAR) for locally advanced rectal cancer
Authors: Koukourakis Michael I , Kavazis Christos , Giagtzidis Axiotis , Mamalis Panagiotis , Tsaroucha Alexandra , Botaitis Sotirios , Giatromanolaki Alexandra , Pitiakoudis Michael
Published: January 2022

Background

despite the advances in preoperative hypofractionated–accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46–50 Gy in 5 weeks) remains a standard adjuvant schedule. The role of hypofractionated–accelerated radiotherapy in a postoperative setting remains largely unexplored.

Methods

eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated–accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12 days. The follow-up of patients alive at the time of analysis ranges from 12–120 months (median 48).

Results

mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P = 0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P = 0.23).

Conclusion

postoperative hypofractionated–accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated–accelerated radiotherapy.
A case report of superior mesenteric artery syndrome
Authors: van Rensburg Anzel Jansen , Ghadiri Marjan
Published: January 2022

Superior mesenteric artery (SMA) syndrome is a rare condition resulting in small bowel obstruction. The third part of the duodenum becomes compressed because of the narrow angle between the aorta and the SMA. Those at risk of developing SMA syndrome include patients who develop rapid weight loss, malignancy, eating disorders, burns, trauma and substance abuse. We present a case of a 73-year-old man that presented 5 days post a total hip replacement with abdominal pain and profuse bilious vomiting for 2 days. A computed tomography scan of his abdomen showed gross distension of his stomach with an abrupt occlusion of the duodenum at the level of the SMA which was consistent with SMA syndrome. The patient was treated conservatively and was later discharged from surgical services once his symptoms resolved and he was able to tolerate diet.
Asthma management updates
Authors: Galante Christine M.
Published: January 2022

This article discusses recent updates on the clinical management of asthma and outlines ways for nurses to engage patients in the management of their disease.
Hearing Features and Cochlear Implantation Outcomes in Patients With PathogenicMYO15AVariants: a Multicenter Observational Study
Authors: Chen Pey-Yu , Tsai Cheng-Yu , Wu Jiunn-Liang , Li Yi-Lu , Wu Che-Ming , Chen Kuang-Chao , Hwang Chung-Feng , Wu Hung-Pin , Lin Hung-Ching , Cheng Yen-Fu , Lo Ming-Yu , Liu Tien-Chen , Yang Ting-Hua , Chen Pei-Lung , Hsu Chuan-Jen , Wu Chen-Chi
Published: January 2022

Objectives:

Recessive variants in theMYO15Agene constitute an important cause of sensorineural hearing impairment (SNHI). However, the clinical features ofMYO15A-related SNHI have not been systemically investigated. This study aimed to delineate the hearing features and outcomes in patients with pathogenicMYO15Avariants.

Design:

This study recruited 40 patients with biallelicMYO15Avariants from 31 unrelated families. The patients were grouped based on the presence of N-terminal domain variants (N variants). The longitudinal audiological data and for those undergoing cochlear implantation, the auditory and speech performance with cochlear implants, were ascertained and compared between patients with different genotypes.

Results:

At the first audiometric examination, 32 patients (80.0%) presented with severe to profound SNHI. Patients with at least one allele of the N variant exhibited significantly better hearing levels than those with biallelic non-N variants (78.2 ± 23.9 dBHL and 94.7 ± 22.8 dBHL, respectively) (p= 0.033). Progressive SNHI was observed in 82.4% of patients with non-profound SNHI, in whom the average progression rate of hearing loss was 6.3 ± 4.8 dBHL/year irrespective of the genotypes. Most of the 25 patients who underwent cochlear implantation exhibited favorable auditory and speech performances post-implantation.

Conclusions:

The hearing features of patients with biallelic pathogenicMYO15Avariants are characterized by severe to profound SNHI, rapid hearing progression, and favorable outcomes with cochlear implants. Periodic auditory monitoring is warranted for these patients to enable early intervention.
Patient Heterogeneity and the J-Curve Relationship Between Time-to-Antibiotics and the Outcomes of Patients Admitted With Bacterial Infection*
Authors: Usher Michael G. , Tourani Roshan , Webber Ben , Tignanelli Christopher J. , Ma Sisi , Pruinelli Lisiane , Rhodes Michael , Sahni Nishant , Olson Andrew P. J. , Melton Genevieve B. , Simon Gyorgy
Published: January 2022

OBJECTIVES:

Sepsis remains a leading and preventable cause of hospital utilization and mortality in the United States. Despite updated guidelines, the optimal definition of sepsis as well as optimal timing of bundled treatment remain uncertain. Identifying patients with infection who benefit from early treatment is a necessary step for tailored interventions. In this study, we aimed to illustrate clinical predictors of time-to-antibiotics among patients with severe bacterial infection and model the effect of delay on risk-adjusted outcomes across different sepsis definitions.

DESIGN:

A multicenter retrospective observational study.

SETTING:

A seven-hospital network including academic tertiary care center.

PATIENTS:

Eighteen thousand three hundred fifteen patients admitted with severe bacterial illness with or without sepsis by either acute organ dysfunction (AOD) or systemic inflammatory response syndrome positivity.

MEASUREMENTS AND MAIN RESULTS:

The primary exposure was time to antibiotics. We identified patient predictors of time-to-antibiotics including demographics, chronic diagnoses, vitals, and laboratory results and determined the impact of delay on a composite of inhospital death or length of stay over 10 days. Distribution of time-to-antibiotics was similar across patients with and without sepsis. For all patients, a J-curve relationship between time-to-antibiotics and outcomes was observed, primarily driven by length of stay among patients without AOD. Patient characteristics provided good to excellent prediction of time-to-antibiotics irrespective of the presence of sepsis. Reduced time-to-antibiotics was associated with improved outcomes for all time points beyond 2.5 hours from presentation across sepsis definitions.

CONCLUSIONS:

Antibiotic timing is a function of patient factors regardless of sepsis criteria. Similarly, we show that early administration of antibiotics is associated with improved outcomes in all patients with severe bacterial illness. Our findings suggest identifying infection is a rate-limiting and actionable step that can improve outcomes in septic and nonseptic patients.
Influencing factors for tracheostomy in patients with acute traumatic C3–C5 spinal cord injury and acute respiratory failure
Authors: Yu Wen-Kuang , Chen Yu-Chun , Chen Wei-Chih , Yi-Fong Su Vincent , Yang Kuang-Yao , Kou Yu Ru
Published: January 2022

Background:

Patients with traumatic spinal cord injury (SCI) at C3–C5 have a wide range of tracheostomy rates (27%-75%), and the influencing factors for tracheostomy remain unclear. We conducted a retrospective case-control study to identify the influencing factors for tracheostomy in this subset of patient population.

Methods:

A total of 101 acute traumatic C3–C5 SCI patients with acute respiratory failure requiring translaryngeal intubation and invasive mechanical ventilation (IMV) for more than 48 hours were identified and divided into the no tracheostomy (No-TCO, n = 59) and tracheostomy group (TCO, n = 42) groups. Clinical data were retrospectively reviewed and analyzed.

Results:

Compared with the No-TCO patients, the TCO patients had a higher proportion of C3 level injury, lower Glasgow Coma Scale (GCS), and lower blood hemoglobin levels at admission. During the first weaning attempt, the TCO patients had lower levels of maximal inspiratory pressure, maximal expiratory pressure, and minute ventilation but had a higher level of rapid shallow breathing index (RSBI). The TCO patients had longer durations of IMV, ICU stay, and hospitalization compared with the No-TCO patients. Moreover, due to prolonged IMV, the TCO patients had a higher incidence of complications, including ventilator-associated pneumonia, bacteremia, urinary tract infection, and acute kidney injury compared with the No-TCO patients. Multivariate logistic regression analysis revealed that low GCS at admission and high initial RSBI were independent risk factors for tracheostomy. Importantly, a combination of these two influencing factors synergistically increased the odds ratio for tracheostomy.

Conclusion:

Low GCS at admission and high initial RSBI are two independent influencing factors that synergistically impact tracheostomy in our patients. These findings are helpful for making the decision of performing tracheostomy in this subset of patient population.
SARS-CoV-2 vaccination in patients with inflammatory bowel disease: A systemic review and meta-analysis
Authors: Sung Kuan-Yi , Chang Tien-En , Wang Yen-Po , Lin Chun-Chi , Chang Chung-Yu , Hou Ming-Chih , Lu Ching-Liang
Published: January 2022

Background:

In the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination has been effective in preventing COVID-19 infections and related mortality. The SARS-CoV-2 vaccination was also recommended by the international society for patients with inflammatory bowel disease (IBD). However, IBD patients were not recruited in prospective randomized clinical vaccine studies. To evaluate the efficacy and safety of SARS-CoV-2 vaccination in IBD patients, we conducted this systemic review and meta-analysis.

Methods:

We systematically searched PubMed, Medline, and the Cochrane Library for studies published between January 1, 2019, and September 9, 2021. Studies written in English reported the efficacy, seroconversion (anti–SARS-CoV-2 anti-spike (S) antibody titer beyond the threshold) rate, and adverse events after the SARS-CoV-2 vaccination in IBD patients. We extracted the author, date, study design, country, types of SARS-CoV-2 vaccination, number of IBD patients receiving SARS-CoV-2 vaccinations, and study outcomes. Published data from the enrolled studies were pooled to determine effect estimates. The study protocol was registered in PROSPERO (CRD42021264993).

Results:

We analyzed findings from 27 454 IBD patients who received SARS-CoV-2 vaccinations in 11 studies that met the inclusion criteria. The post–SARS-CoV-2 vaccination COVID-19 infection rate was comparable between the IBD patients and non-IBD patients (odds ratio [OR], 1.28 [95% CI, 0.96–1.71]) and higher in nonvaccinated IBD patients compared with vaccinated IBD patients (OR, 8.63 [95% CI, 5.44–13.37]). The adverse event rate, severe adverse events, and mortality after the SARS-CoV-2 vaccination were 69%, 3%, and 0%, respectively.

Conclusion:

The SARS-CoV-2 vaccine is effective and tolerated in preventing COVID-19 infections in IBD patients. Over 98% of patients had seroconversion after receiving all doses of the SARS-CoV-2 vaccination, and the influence of biologics on vaccination was limited. The SARS-CoV-2 vaccination is recommended for IBD patients.
Ischemic Pancreatitis Is an Important Cause of Acute Pancreatitis in the Intensive Care Unit
Authors: Baldursdottir Maria B. , Andresson Johannes A. , Jonsdottir Sigrun , Benediktsson Halldor , Kalaitzakis Evangelos , Bjornsson Einar S.
Published: January 2022

Background:

Ischemic pancreatitis (IP) has mainly been described in case reports. The aims of the study were to assess the frequency, clinical characteristics and outcomes in patients with IP among patients hospitalized in the intensive care unit (ICU) for acute pancreatitis (AP).

Methods:

All patients with first time AP between 2011 and 2018 in the ICU of Landspitali Hospital, Iceland were retrospectively included. IP as an etiology required a clinical setting of circulatory shock, arterial hypotension, hypovolemia and/or arterial hypoxemia [PaO2 of 60 mm Hg (8.0 kPa), or less] before the diagnosis of AP without prior history of abdominal pain to this episode. Other causes of AP were ruled out. IP patients were compared with patients with AP of other etiologies, also hospitalized in the ICU.

Results:

Overall 67 patients with AP were identified (median age 60 y, 37% females), 31% idiopathic, 24% alcoholic, 22% IP, 15% biliary, and 8% other causes. Overall, 15 (22%) fulfilled the predetermined criteria for IP, 9 males (64%), median age 62 years (interquartile range: 46 to 65). IP was preceded mainly by systemic shock (73%). Other causes included dehydration, hypoxia, or vessel occlusion to the pancreas. Necrosis of the pancreas was rare with one patient requiring pancreatic necrosectomy. Inpatient mortality was higher among patients with IP than in other patients with AP (33% vs. 14%, P=0.12).

Conclusions:

IP was found in a significant proportion of AP patients hospitalized in the ICU. The main causes of IP were systemic shock and hypoxia. IP was associated with ∼30% mortality.
Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms
Authors: Gala Khushboo , Stocker Abigail , Tu Yixi , Nguyen Vincent , McElmurray Lindsay , Cooper Kelly , Chhabra Garvit , Mathur Prateek , Vedanarayanan Vetta , Pinkston Christina , Abell Thomas L.
Published: January 2022

Introduction:

Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG.

Materials and Methods:

We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation.

Results:

Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P=0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P=0.09).

Conclusions:

In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.
The impact of compensated and decompensated cirrhosis on the postoperative outcomes of patients undergoing hernia repair: a propensity score-matched analysis of 2011–2017 US hospital database
Authors: Lee David Uihwan , Hastie David Jeffrey , Lee Ki Jung , Hongyuan Fan Gregory , Ann Addonizio Elyse , Kwon Jean , Karagozian Raffi
Published: January 2022

Background and aims

Since there is clinical overlap between populations with cirrhosis and those who require hernia repair (i.e. due to stretching of abdominal walls), we systematically evaluate the effects of cirrhosis on post-hernia repair outcomes.

Methods

2011–2017 National Inpatient Sample was used to identify patients who underwent hernia repair (included: inguinal, umbilical, and other abdominal hernia repairs). The population was stratified into those with compensated cirrhosis (CC), decompensated cirrhosis (DC), and no cirrhosis; hepatic decompensation was defined as those with portal hypertension, ascites, and varices. The propensity score was used to match the no-cirrhosis controls to CC and DC using the 1:1 nearest neighbor mechanism. Endpoints included mortality, length of stay, costs, and complications.

Results

Postmatch, there were 392/446 CC/DC with equal number controls in those undergoing inguinal hernia repair, 714/1652 CC/DC with equal number controls in those undergoing umbilical hernia repair, and 784/702 CC/DC. In multivariate, for inguinal repair, there was no difference in mortality [CC vs. no-cirrhosis aOR 2.61, 95% confidence interval (CI) 0.50–13.52; DC vs. no-cirrhosis: aOR 1.75, 95% CI 0.84–3.63]. For umbilical repair, there was no difference in mortality for CC vs. no-cirrhosis: aOR 0.94, 95% CI 0.36–2.42); however, DC had higher mortality (aOR 2.86, 95% CI 1.76–4.63) when comparing DC vs. no-cirrhosis. For other abdominal repairs, there was no difference in mortality for CC vs. no-cirrhosis (aOR 1.10, 95% CI 0.54–2.23); however, DC had higher mortality (P < 0.001, aOR 2.58, 95% CI 1.49–4.46) when comparing DC vs. no-cirrhosis.

Conclusion

This study demonstrates that the presence of DC affects postoperative survival in patients undergoing umbilical or other abdominal hernia repair surgery.
De-escalation of biological therapy in inflammatory bowel disease patients following prior dose escalation
Authors: Thomas Pepijn W. A. , Smits Lisa J. T. , Te Groen Maarten , West Rachel L. , Russel Maurice G. V. M. , Jansen Jeroen M. , Römkens Tessa E. H. , Hoentjen Frank
Published: January 2022

Background

Limited data are available on biological therapy de-escalation after prior escalation in inflammatory bowel disease (IBD) patients. This study aimed to assess the frequency and success rate of de-escalation of biological therapy in IBD patients after prior dose escalation and to evaluate which measures are used to guide de-escalation.

Methods

This multicentre retrospective cohort study enrolled IBD patients treated with infliximab (IFX), adalimumab (ADA) or vedolizumab (VEDO) in whom therapy was de-escalated after prior biological escalation. De-escalations were considered pharmacokinetic-driven if based on clinical symptoms combined with therapeutic or supratherapeutic trough levels, and disease activity-driven if based on faecal calprotectin less than or equal to 200 µg/g or resolution of perianal fistula drainage or closure or endoscopic remission. Successful de-escalation was defined as remaining on the same or lower biological dose for greater than or equal to 6 months after de-escalation without the need for corticosteroids.

Results

In total, 206 IFX users, 85 ADA users and 55 VEDO users underwent therapy escalation. Of these patients, 34 (17%) on IFX, 18 (21%) on ADA and 8 (15%) on VEDO underwent therapy de-escalation. De-escalation was successful in 88% of IFX patients, 89% of ADA and 100% of VEDO. The probability of remaining on the de-escalated regimen or further de-escalation after 1 year was 85% for IFX, 62% for ADA and 100% for VEDO. Disease activity-driven de-escalations were more often successful (97%) than pharmacokinetic- and no marker-driven de-escalations (76%); P = 0.017.

Conclusion

De-escalation after biological dose escalation was successful in the majority of carefully selected IBD patients. Objective assessment of remission increased the likelihood of successful de-escalation.
Financial Hardship and Quality of Life Among Patients With Advanced Cancer Receiving Outpatient Palliative Care
Authors: Belcher Sarah M. , Lee Haerim , Nguyen Janet , Curseen Kimberly , Lal Ashima , Zarrabi Ali John , Gantz Lindsay , Rosenzweig Margaret Q. , Hill Jennifer L. , Yeager Katherine A.
Published: January 2022

Background

Patients with advanced cancer are increasingly experiencing financial hardship (FH) and associated negative health outcomes.

Objective

The aims of this study were to describe FH and explore its relationship to quality of life (QOL) in patients with advanced cancer receiving outpatient palliative care (PC).

Methods

Validated questionnaires assessed FH, QOL dimensions, symptom burden, and sociodemographic and clinical characteristics. Descriptive statistics characterized the sample and described FH. Pearson correlation and linear regression assessed relationships between FH and QOL.

Results

The average participant (n = 78) age was 56.6 (SD, 12.2) years. Most were female (56.4%), White (50%) or Black (46.2%), and had a range of education, partner statuses, and cancer diagnoses. Median time since cancer diagnosis was 35.5 months (interquartile range, 9-57.3 months). Highest mean symptom burden scores were for pain (2.5 [SD, 1.0]) and fatigue (2.0 [SD, 1.1]), on a 0- to 3-point scale (higher score representing worse symptom burden). The median COST (COmphrehensive Score for financial Toxicity) score was 15.0 (interquartile range, 9.0-23.0). Most (70%) had some (n = 43) or extreme (n = 9) difficulty paying for basic needs. Greater than 28% (n = 21) incurred cancer-related debt. Multivariate models indicated that FH negatively affected role limitations due to physical health (P = .008), pain (P = .003), and emotional well-being (P = .017) QOL dimensions.

Conclusions

Financial hardship, QOL, and symptom burden scores demonstrate need for continued support for and research among patients with advanced cancer. Data support links between FH and important QOL dimensions. Larger, longitudinal studies are needed to understand how FH affects QOL in patients with advanced cancer.

Implications for Practice

Proactive financial assessment and interventions are needed to support patients with advanced cancer experiencing the cumulative effects of cancer and its treatment.
Impact of HIV on Cognitive Performance in Professional Drivers
Authors: Gouse Hetta , Masson Catherine J. , Henry Michelle , Dreyer Anna , Robbins Reuben N. , Kew Greg , Joska John A. , London Leslie , Marcotte Thomas D. , Thomas Kevin G. F.
Published: January 2022

Background:

The intellectually demanding modern workplace is often dependent on good cognitive health, yet there is little understanding of how neurocognitive dysfunction related to HIV presents in employed individuals working in high-risk vocations such as driving. HIV-associated neurocognitive impairment is also associated with poorer long-term cognitive, health, and employment outcomes.

Setting:

This study, set in Cape Town, South Africa, assessed the effects of HIV on neuropsychological test performance in employed male professional drivers.

Method:

We administered a neuropsychological test battery spanning 7 cognitive domains and obtained behavioral data, anthropometry, and medical biomarkers from 3 groups of professional drivers (68 men with HIV, 55 men with cardiovascular risk factors, and 81 controls). We compared the drivers' cognitive profiles and used multiple regression modeling to investigate whether between-group differences persisted after considering potentially confounding sociodemographic and clinical variables (ie, income, home language, depression, and the Framingham risk score).

Results:

Relative to other study participants, professional drivers with HIV performed significantly more poorly on tests assessing processing speed (P < 0.003) and attention and working memory (P = 0.018). Group membership remained a predictor of cognitive performance after controlling for potential confounders. The cognitive deficits observed in men with HIV were, however, largely characterized as being mild or asymptomatic. Consistent with this characterization, their relatively poor performance on neuropsychological testing did not generalize to self-reported impairment on activities of daily living.

Conclusion:

Drivers with HIV may be at risk of poorer long-term health and employment outcomes. Programs that monitor and support their long-term cognitive health are needed.
New-onset Oscillopsia in a Patient With a History of Pontine Stroke
Authors: Kabanovski Anna , Donaldson Laura , Margolin Edward
Published: January 2022

A 69-year-old man with a history of pontine hemorrhage 2 years ago noticed binocular vertical diplopia after the stroke. On examination, there was a small-angle incomitant left hyperdeviation that did not fit the 3-step test for fourth nerve palsy and incyclotorsion of the higher eye. On motility testing, there was an obvious pendular nystagmus. Resting tremor of the right hand was noticed on neurological examination. Examination of the oropharynx revealed rhythmic oscillations of the soft palate synchronous with the eye oscillations and hand tremor. These findings established a diagnosis of oculopalatal myoclonus (OPM). Although OPM is a well-described entity, this case is unique because the patient was completely asymptomatic from OPM and did not complain of oscillopsia but was very bothered by vertical diplopia because of skew deviation. It also demonstrates that OPM may coexist with skew deviation because anatomically vestibulo–ocular pathway is close to the triangle of Guillain−Mollaret and patients with lesions in one pathway should be examined for abnormalities in the other. Finally, it reminds us about the importance of monitoring patients with a history of brainstem insults for emergence of synchronous tremors years later and that simple maneuver-like ex/amining oropharynx may provide a clear diagnosis.
Postinfectious SARS-CoV-2 Opsoclonus-Myoclonus-Ataxia Syndrome
Authors: Nelson Jodi L. , Blume Gregory M. , Bansal Saurabh K. , Kaufman Jacqueline R. , Woods Florence R. , Zhang Xiaojun , Kattah Jorge C.
Published: January 2022

Background:

The opsoclonus-myoclonus-ataxia syndrome (OMAS) represents a pathophysiology and diagnostic challenge. Although the diverse etiologies likely share a common mechanism to generate ocular, trunk, and limb movements, the underlying cause may be a paraneoplastic syndrome, as the first sign of cancer, or may be a postinfectious complication, and thus, the outcome depends on identifying the trigger mechanism. A recent hypothesis suggests increased GABAA receptor sensitivity in the olivary-oculomotor vermis–fastigial nucleus—premotor saccade burst neuron circuit in the brainstem. Therefore, OMAS management will focus on immunosuppression and modulation of GABAA hypersensitivity with benzodiazepines.

Methods:

We serially video recorded the eye movements at the bedside of 1 patient with SARS-CoV-2–specific Immunoglobulin G (IgG) serum antibodies, but twice-negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR). We tested cerebrospinal fluid (CSF), serum, and nasopharyngeal samples. After brain MRI and chest, abdomen, and pelvis CT scans, we treated our patient with clonazepam and high-dose Solu-MEDROL, followed by a rituximab infusion after her formal eye movement analysis 10 days later.

Results:

The recordings throughout her acute illness demonstrated different eye movement abnormalities. While on high-dose steroids and clonazepam, she initially had macrosaccadic oscillations, followed by brief ocular flutter during convergence the next day; after 10 days, she had bursts of opsoclonus during scotopic conditions with fixation block but otherwise normal eye movements. Concern for a suboptimal response to high-dose Solu-MEDROL motivated an infusion of rituximab, which induced remission. An investigation for a paraneoplastic etiology was negative. CSF testing showed elevated neuron-specific enolase. Serum IgG to Serum SARS-CoV2 IgG was elevated with negative RT-PCR nasopharyngeal testing.

Conclusion:

A recent simulation model of macrosaccadic oscillations and OMAS proposes a combined pathology of brainstem and cerebellar because of increased GABAA receptor sensitivity. In this case report, we report 1 patient with elevated CSF neuronal specific enolase, macrosaccadic oscillations, ocular flutter, and OMAS as a SARS-CoV-2 postinfectious complication. Opsoclonus emerged predominantly with fixation block and suppressed with fixation, providing support to modern theories on the mechanism responsible for these ocular oscillations involving cerebellar-brainstem pathogenesis.
Schizophrenia-associated somatic copy number variants from 12,834 cases reveal contribution to risk and recurrent, isoform-specific NRXN1 disruptions
Authors: Maury Eduardo A. , Sherman Maxwell A. , Genovese Giulio , Gilgenast Thomas G. , Rajarajan Prashanth , Flaherty Erin , Akbarian Schahram , Chess Andrew , McCarroll Steven A. , Loh Po-Ru , Phillips-Cremins Jennifer E. , Brennand Kristen J. , Walters James T. R. , O’ Donovan Michael , Sullivan Patrick ,   Psychiatric Genomic Consortium Schizophrenia and CNV workgroup,   Brain Somatic Mosaicism Network, Sebat Jonathan , Lee Eunjung A. , Walsh Christopher A.
Published: January 2022

While inherited and de novo copy number variants (CNV) have been implicated in the genetic architecture of schizophrenia (SCZ), the contribution of somatic CNVs (sCNVs), present in some but not all cells of the body, remains unknown. Here we explore the role of sCNVs in SCZ by analyzing blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls. sCNVs were more common in cases (0.91%) than in controls (0.51%, p = 2.68e-4). We observed recurrent somatic deletions of exons 1-5 of the NRXN1 gene in 5 SCZ cases. Allele-specific Hi-C maps revealed ectopic, allele-specific loops forming between a potential novel cryptic promoter and non-coding cis regulatory elements upon deletions in the 5’ region of NRXN1. We also observed recurrent intragenic deletions of ABCB11, a gene associated with anti-psychotic response, in 5 treatment-resistant SCZ cases. Taken together our results indicate an important role of sCNVs to SCZ risk and treatment-responsiveness.
Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants
Authors: Miyamoto Sho , Arashiro Takeshi , Adachi Yu , Moriyama Saya , Kinoshita Hitomi , Kanno Takayuki , Saito Shinji , Katano Harutaka , Iida Shun , Ainai Akira , Kotaki Ryutaro , Yamada Souichi , Kuroda Yudai , Yamamoto Tsukasa , Ishijima Keita , Park Eun-Sil , Inoue Yusuke , Kaku Yoshihiro , Tobiume Minoru , Iwata-Yoshikawa Naoko , Shiwa-Sudo Nozomi , Tokunaga Kenzo , Ozono Seiya , Hemmi Takuya , Ueno Akira , Kishida Noriko , Watanabe Shinji , Nojima Kiyoko , Seki Yohei , Mizukami Takuo , Hasegawa Hideki , Ebihara Hideki , Maeda Ken , Fukushi Shuetsu , Takahashi Yoshimasa , Suzuki Tadaki
Published: January 2022

Background

The immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories.

Methods

The neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination.

Findings

The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies.

Conclusions

Immune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants.

Funding

This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
Association between having a pregnancy complicated by vaginal bleeding and risk of cancer
Authors: Dudukina Elena , Horváth-Puhó Erzsébet , Sørensen Henrik Toft , Ehrenstein Vera
Published: January 2022

Background

A full-term pregnancy is associated with a lower cancer risk. The risk of cancer in women with vaginal bleeding in pregnancy is unknown.

Methods

We conducted a registry-based cohort study (1995-2017) in Denmark. We included pregnancies (n=37 082) affected by vaginal bleeding (VB) within 20 gestational weeks among 35 514 women, VB-unaffected pregnancies (n=1 363 614) among 783 314 women, pregnancies ending in a termination (n=324 328) among 239 638 women or miscarriage (n=137 104) among 121 353 women. We computed absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidity, and socioeconomic factors using Cox proportional hazards regression.

Results

At the end of the 24-year follow-up, there were 1 320 events among VB-affected cohort, 40 420 events among VB-unaffected cohort, 10 300 events among termination cohort, and 4 790 events among miscarriage cohort. The HR for any cancer was 1.03 (95% CI: 0.97-1.08) when comparing VB-affected vs VB-unaffected pregnancies, 1.03 (95% CI: 0.97-1.09) vs terminations, and 0.90 (95% CI: 0.84-0.95) vs miscarriages. Similar results were obtained for site-specific cancers.

Conclusions

We found no strong evidence for an association between vaginal bleeding in pregnancy and an increased risk of cancer.
Head-to-head comparison of nasal and nasopharyngeal sampling using SARS-CoV-2 rapid antigen testing in Lesotho
Authors: Labhardt Niklaus D , Fernández Lucia González , Katende Bulemba , Muhairwe Josephine , Bresser Moniek , Amstutz Alain , Glass Tracy R , Ruhwald Morten , Sacks Jilian A , Escadafal Camille , Mareka Mathabo , Mookho Mooko Sekhele , de Vos Margaretha , Reither Klaus
Published: January 2022

Objectives

To assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT).

Methods

Individuals ≥5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard.

Results

Out of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration ≤ 3days versus ≤ 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%.

Conclusions

The STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of ≥ 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling.

Highlights

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Prospective study on real-world diagnostic performance of nasal and nasopharyngeal SD Biosensor STANDARD Q COVID-19 Ag Test in 2131 participants in a rural African setting

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The sensitivity of the STANDARD Q COVID-19 Ag Test was below the World Health Organization requirement of ≥ 80% but met the specificity requirement of ≥97%.

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Sensitivity was higher in the following subpopulations: persons with symptoms ≤3 days, and Ct value < 25.

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In head-to-head comparison nasal and nasopharyngeal sampling had comparable sensitivity and specificity and an overall test agreement of 99.4%, indicating that the more convenient nasal sampling could be used for SARS-CoV-2 rapid antigen tests.

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24 of the 2131 participants with COVID-19 symptoms had pulmonary tuberculosis with a positive Xpert Ultra test on sputum.