Persistent Morbidity Research Articles

Negotiating the ambiguity of an (in)authentic working life: a grounded theory study into severe perineal trauma

BackgroundIn Sweden, persistent physical and psychological health problems occur in about three in ten women who sustain severe perineal trauma (SPT) during childbirth. As most Swedish women work outside the home, the question of if and how SPT-related morbidity influences working life needs exploration. This study aims to qualitatively explore how women with persistent SPT-related morbidities experience and conceptualise their problems concerning working life. Further, we theorise the findings by applying Simone de Beauvoir’s feminist framework of immanence and transcendence as well as authentic and inauthentic life.MethodsTen interviews with women recruited via a Swedish social media community for perineal trauma were analysed according to Charmaz’s constructivist approach to grounded theory.ResultsThe theoretical model and related core category ‘Negotiating the ambiguity of an (in)authentic working life’ reflected the women’s negotiations of immanence as ‘the silent covert object’ versus transcendence as the ‘the resourceful overt subject’. The model also mirrored the conflict of (in)authenticity in working life. An inauthentic working life was experienced when women were denied their subjectivity at work or constructed themselves as subjects in denial of their SPT. On the other hand, women who acknowledged their SPT and were constructed as subjects by ‘others’ achieved an authentic working life despite SPT.ConclusionsThe conflicting gendered process of ‘the silent covert object’ versus ‘the resourceful overt subject’ problematised women’s vulnerability at work. Aspects that enable subjectification and transcendence are essential for policymakers, employers, healthcare services, and society to eradicate the taboo of SPT and create a working environment characterised by understanding, support, and flexibility. Further, access to adequate care, sick leave, and occupational rehabilitation are essential. Such measures support transcendence towards an authentic working life and, consequently, a more gender-equal working environment that does not deprive women of career opportunities due to a physical ailment.

Longitudinal DNA methylation analysis of adult-type IDH-mutant gliomas

Diffuse gliomas are the most prevalent malignant primary brain tumors in adults and remain incurable despite standard therapy. Tumor recurrence is currently inevitable, which contributes to a persistent high morbidity and mortality in these patients. In this study, we examined the genome-wide DNA methylation profiles of primary and recurrent adult-type IDH-mutant gliomas to elucidate DNA methylation changes associated with tumor progression (with or without malignant transformation). We analyzed DNA methylation profiles of 37 primary IDH-mutant gliomas and 42 paired recurrences using the DNA methylation EPIC beadChip array. DNA methylation-based classification reflected the tumor progression over time. We observed a methylation subtype switch in a proportion of IDH-mutant astrocytomas; the primary tumors were subclassified as low-grade astrocytomas, which progressed to high-grade astrocytomas in the recurrent tumors. The CNS WHO grade 4 IDH-mutant astrocytomas did not always resemble methylation subclasses of higher grades. The number of differentially methylated CpG sites increased over time, and astrocytomas accumulated more differentially methylated CpG sites than oligodendrogliomas during tumor progression. Few differentially methylated CpG sites were shared between patients. We demonstrated that DNA methylation profiles are mostly maintained during IDH-mutant glioma progression, but CpG site-specific methylation alterations can occur.

Association of persistent morbidity after radiotherapy with quality of life in locally advanced cervical cancer survivors

PurposeTo quantify the association of persistent morbidity with different aspects of quality of life (QOL) in locally advanced cervical cancer (LACC) survivors. Material and methodsLongitudinal outcome from the EMBRACE-I study was evaluated. Patient-reported symptoms and QOL were prospectively scored (EORTC-C30/CX24) at baseline and regular follow-ups. Physician-assessed symptoms were also reported (CTCAEv.3). Persistent symptoms were defined if present in at least half of the follow-ups. QOL items were linearly transformed into a continuous scale. Linear mixed-effects models (LMM) were applied to evaluate and quantify the association of persistent symptoms with QOL. Overall QOL deterioration was evaluated by calculating the integral difference in QOL over time obtained with LMM for patients without and with persistent symptoms. ResultsOut of 1416 patients enrolled, 741 with baseline and ≥ 3 late follow-ups were analyzed (median 59 months). Proportions of persistent EORTC symptoms ranged from 21.8 % to 64.9 % (bowel control and tiredness). For CTCAE the range was 11.3–28.6 % (limb edema and fatigue). Presence of any persistent symptom was associated with QOL, although with varying magnitude. Role functioning and Global health/QOL were the most impaired aspects. Fatigue and pain showed large differences, with reductions of around 20 % for most of the QOL aspects. Among organ-related symptoms, abdominal cramps showed the largest effect. ConclusionPersistent symptoms are associated with QOL reductions in LACC survivors. Organ-related symptoms showed smaller differences than general symptoms such as fatigue and pain. In addition to optimizing treatment to minimize organ-related morbidity, effort should be directed towards a more comprehensive and targeted morbidity management.

Prevalence of Diarrhea, Intestinal Parasites, and Associated Factors Among Under-Five Children in Dabat District, Northwest Ethiopia: Multicenter Cross-sectional Study.

Despite global interventions to prevent and control diarrhea, it remains a public health problem leading to childhood morbidity and mortality majorly in developing countries. According to the World Health Organization, data from 2021 indicated that diarrheal disease is responsible for 8% of deaths in children under the age of 5. In the world, more than 1 billion under-five children live in poverty, social exclusion, and discrimination affected by intestinal parasitic infections and diarrhea disease. In sub-Saharan African countries like Ethiopia, diarrheal diseases and parasite infections continue to cause significant and persistent morbidity and mortality in under-five children. Therefore, the purpose of this study was to assess the prevalence and associated factors of intestinal parasites and diarrheal diseases in children under the age of 5 years in Dabat District, Northwest Ethiopia in 2022. A community-based, cross-sectional study was carried out from September 16 to August 18th 2022. Four hundred households with at least one child under the age of 5 years were recruited by simple random sampling technique. Sociodemographic, clinical, and behavioral factors were also collected using pretested interviewer-administered questionnaires. Data was entered into Epi-data version 3.1 and exported to Statistical Package for Social Science (SPSS) version 25 for analysis. Binary logistic regression was performed to identify factors associated with diarrhea and intestinal parasitic infections. The level of significance was computed at a P-value ⩽ .05. Descriptive statistics such as frequency and other summary statistics were used for describing sociodemographic variables and determining the prevalence of diarrhea and intestinal parasites. Tables, figures, and texts were used to present the findings. The variables having a P-value of less than .2 in the bivariable analysis were entered into the multivariable analysis at a P-value of ⩽.5. According to this study, the prevalence of diarrhea and intestinal parasites among under-five children was 20.8% (95% CI: [16.8-37.8] and 32.5% (95% CI: [28.6, 37.8], respectively. In multivariable logistic analysis at a P-value of ⩽.5, the educational level of mothers (Adjusted odds ratio [AOR]: 3.7, 95% CI: [1.52, 8.95], residence (AOR: 4.7, 95% CI: [1.52, 8.09]), undernutrition (AOR: 3.6, 95% CI: [1.09, 11.3]), latrine availability (AOR:3.9, 95% CI: [1.23, 9.56]), types of the latrine (AOR: 5.9, 95% CI: [3.42, 11.66]), water treatment (AOR = 7.6; 95% CI: [6.4, 12.7]), eating uncooked vegetable or fruits (AOR = 4.6; 95% CI: [1.025, 15.2]), and source of water (AOR = 4.5; 95% CI: [2.32,8.92]) were significantly associated with diarrheal disease. Intestinal parasitic infection was also significantly associated with undernutrition (AOR = 3.9; 95% CI: [1.09, 9.67]), latrine availability (AOR = 2.1; 95% CI:[1.32, 9.32]), types of the latrine (AOR = 2.8; 95% CI: [1.92, 8.12]) residence (AOR = 4.7; 95% CI: [1.52, 8.09]), water treatment, source of water for drinking (AOR = 4.5; 95% CI: [2.32, 8.92]), eating uncooked vegetables or fruits (AOR = 6.7:95% CI: [3.9, 9.8]), and deworming children with anti-parasitic medication (AOR = 2.4; 95% CI: [1.34, 5.62]), washing hands after latrine used (AOR = 2.2: 95% CI: [1.06, 3.86]). The prevalence of diarrhea and intestinal parasite among under-five children was 20.8% and 32.5%, respectively. Undernutrition, latrine availability, types of latrines, residence, eating uncooked vegetables or fruits, and source of water for drinking and water treatment were associated with intestinal parasitic infection and diarrheal disease. Deworming children with antiparasitic medications and washing hands after latrine use was also significantly associated with parasitic infection. Hence, awareness creation activities on latrine utilization and building, keeping personal hygiene, safe water supply, feeding cooked vegetables or fruits, taking anti-parasitic medications, practice hand washing habit after toilet use are strongly recommended.

Temporal and thermal profiling of the Toxoplasma proteome implicates parasite Protein Phosphatase 1 in the regulation of Ca2+-responsive pathways.

Apicomplexan parasites cause persistent mortality and morbidity worldwide through diseases including malaria, toxoplasmosis, and cryptosporidiosis. Ca2+ signaling pathways have been repurposed in these eukaryotic pathogens to regulate parasite-specific cellular processes governing the replicative and lytic phases of the infectious cycle, as well as the transition between them. Despite the presence of conserved Ca2+-responsive proteins, little is known about how specific signaling elements interact to impact pathogenesis. We mapped the Ca2+-responsive proteome of the model apicomplexan Taxoplasma gondii via time-resolved phosphoproteomics and thermal proteome profiling. The waves of phosphoregulation following PKG activation and stimulated Ca2+ release corroborate known physiological changes but identify specific proteins operating in these pathways. Thermal profiling of parasite extracts identified many expected Ca2+-responsive proteins, such as parasite Ca2+-dependent protein kinases. Our approach also identified numerous Ca2+-responsive proteins that are not predicted to bind Ca2+, yet are critical components of the parasite signaling network. We characterized protein phosphatase 1 (PP1) as a Ca2+-responsive enzyme that relocalized to the parasite apex upon Ca2+ store release. Conditional depletion of PP1 revealed that the phosphatase regulates Ca2+ uptake to promote parasite motility. PP1 may thus be partly responsible for Ca2+-regulated serine/threonine phosphatase activity in apicomplexan parasites.

Variations in comorbidity burden in people with type 2 diabetes over disease duration: A population-based analysis of real world evidence.

SummaryBackgroundThe prevalence of type 2 diabetes (T2DM) is increasing, but increasing longevity among persons with diagnosed diabetes may be is associated with more extensive and diverse types of morbidity. The extent and breadth of morbidity and how this varies across sub-groups is unclear and could have important clinical and public health implications. We aimed to estimate comorbidity profiles in people with T2DM and variations across sub-groups and over time.MethodsWe identified approximately 224,000 people with T2DM in the Discover-NOW dataset, a real-world primary care database from 2000 to 2020 covering 2.5 million people across North-West London, England, linked to hospital records. We generated a mixed prevalence and incidence study population through repeated annual cross sections, and included a broad set of 35 comorbidities covering traditional T2DM conditions, emerging T2DM conditions and other common conditions.We estimated annual age-standardised prevalence of comorbidities, over the course of the disease in people with T2DM and several sub-groups.FindingsMultimorbidity (two or more chronic conditions) is common in people with T2DM and increasing, but the comorbidity profiles of people with T2DM vary substantially. Nearly 30% of T2DM patients had three or more comorbidities at diagnosis, increasing to 60% of patients ten years later. Two of the five commonest comorbidities at diagnosis were traditional T2DM conditions (hypertension (37%) and ischaemic heart disease (10%)) the other three were not (depression (15%), back pain (25%) and osteoarthritis (11%)). The prevalence of each increased during the course of the disease, with more than one in three patients having back pain and one in four having depression ten years post diagnosis.People with five or more comorbidities at diagnosis had higher prevalence of each of the 35 comorbidities. Hypertension (73%) was the commonest comorbidity at diagnosis in this group; followed by back pain (69%), depression (67%), asthma (45%) and osteoarthritis (36%). People with obesity at diagnosis had substantially different comorbidity profiles to those without, and the five commonest comorbidities were 50% more common in this group.InterpretationPreventative and clinical interventions alongside care pathways for people with T2DM should transition to reflect the diverse set of causes driving persistent morbidity. This would benefit both patients and healthcare systems alike.FundingThe study was funded by the National Institute for Health and Care Excellence (NICE).

Analysis of risk factors for venous air embolism in the semisitting position and its impact on outcome in a consecutive series of 740 patients.

Routine use of the semisitting position, which offers several advantages, remains a matter of debate. Venous air embolism (VAE) is a potentially serious complication associated with the semisitting position. In this study, the authors aimed to investigate the safety of the semisitting position by analyzing data over a 20-year period. The incidence of VAE and its perioperative management were analyzed retrospectively in a consecutive series of 740 patients who underwent surgery between 1996 and 2016. The occurrence of VAE was defined by detection of bubbles on transthoracic Doppler echocardiography (TTDE) or transesophageal echocardiography (TEE) studies, a decrease of end-tidal CO2 (ETCO2) by 4 mm Hg or more, and/or an unexplained drop in systolic arterial blood pressure (≥ 10 mm Hg). From 1996 until 2013 TTDE was used, and from 2013 on TEE was used. The possible risk factors for VAE and its impact on surgical performance were analyzed. There were 404 women and 336 men with a mean age at surgery of 49 years (range 1-87 years). Surgery was performed for infratentorial lesions in 709 patients (95.8%), supratentorial lesions in 17 (2.3%), and cervical lesions in 14 (1.9%). The most frequent pathology was vestibular schwannoma. TEE had a higher sensitivity than TTDE. While TEE detected VAE in 40.5% of patients, TTDE had a detection rate of 11.8%. Overall, VAE was detected in 119 patients (16.1%) intraoperatively. In all of these patients, VAE was apparent on TTDE or TEE. Of those, 23 patients also had a decrease of ETCO2, 18 had a drop in blood pressure, and 23 had combined decreases in ETCO2 and blood pressure. VAE was detected in 24% of patients during craniotomy before opening the dura mater, in 67% during tumor resection, and in 9% during wound closure. No risk factors were identified for the occurrence of VAE. Two patients had serious complications due to VAE. Surgical performance in vestibular schwannoma surgery was not affected by the presence of VAE. This study shows that the semisitting position is overall safe and that VAE can be managed effectively. Persistent morbidity is very rare. The authors suggest that the semisitting position should continue to have a place in the standard armamentarium of neurological surgery.

IDF21-0404 Variations in comorbidity burden in patients with type 2 diabetes and impacts on healthcare resource usage and costs

Background: The prevalence of type 2 diabetes (T2DM) is increasing, and cause of death and complications in this patient group are now much broader than the established macro and micro vascular complications. However, the extent and breadth of morbidity and how this varies across sub-groups is unclear. Aim: We aimed to estimate comorbidity profiles in patients with T2DM, variations across sub-groups and over the course of the disease, and associated healthcare resource use (HCRU) and health system costs. Method: We identified approximately 224,000 patients with T2DM in the Discover-NOW dataset, a real-world primary care database from 2000-2020 covering 2.5 million people across North West London, England, linked to hospital records. We generated a mixed prevalence and incidence study population through repeated annual cross sections, and included a broad set of 35 comorbidities covering traditional T2DM complications, emerging conditions and other common comorbidities. HCRU and costs across primary and secondary care included inpatient admissions, outpatient appointments and Emergency Department attendances. We estimated annual age-standardised prevalence of comorbidities, HCRU and costs over the course of the disease in patients with T2DM and several sub-groups, including by age, gender, and those with specific comorbidities at baseline. Results: Multimorbidity (two or more chronic conditions) is common in patients with T2DM and increasing, but the comorbidity profiles of patients with T2DM vary substantially. Nearly 30% of T2DM patients had three or more comorbidities at diagnosis, increasing to 60% of patients ten years later. Two of the five commonest comorbidities at diagnosis were expected (hypertension (37%) and ischaemic heart disease (10%)) the other three were not (depression (25%), back pain (15%) and osteoarthritis (11%)). The prevalence of each increased during the course of the disease, with more than one in three patients having back pain and one in four having depression ten years post diagnosis. Patients with five or more comorbidities at diagnosis had higher prevalence of each of the 35 comorbidities. Hypertension (73%) was the commonest comorbidity at diagnosis in this group; followed by back pain (69%), depression (67%), asthma (45%) and osteoarthritis (36%). Patients with obesity at diagnosis had substantially different comorbidity profiles to those without, and the five commonest comorbidities were 50% more common in this group. Between 2015 and 2019, the number of HCRU appointments per T2DM patient increased from 14.6 to 16.7. Annual costs increased from £1,300 to £2,100 over the same period. Inpatient admissions comprised 63% of total costs, the number of outpatient appointments increased over the study period, and other HCRU types remained stable. HCRU and costs were approximately 15-20% higher in women compared to men and over twice as high in adults >75 years (£2,900) compared to adults <55 years (£1,100). The largest differences were between patients with five or more comorbidities at diagnosis (29 HCRU events per year, £4,400) compared to those with two comorbidities or fewer (12 HCRU events, £700.) Discussion: Preventative and clinical measures alongside care pathways for patients with T2DM should transition to reflect the diverse set of causes driving persistent morbidity. This would benefit both patients and reduce increasing healthcare costs alike.

SNP-SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children.

We studied associations of persistent respiratory morbidity (PRM) at 6 and 12 months after acute respiratory failure (ARF) in previously healthy children with single-nucleotide polymorphisms (SNPs) of surfactant protein (SP) genes. Of the 250 enrolled subjects, 155 and 127 were followed at 6 and 12 months after an ARF episode, respectively. Logistic regression analysis and SNP–SNP interaction models were used. We found that 1) in the multivariate analysis, an increased risk at 6 and 12 months was associated with rs1124_A and rs4715_A of SFTPC, respectively; 2) in a single SNP model, increased and decreased risks of PRM at both timepoints were associated with rs1124 of SFTPC and rs721917 of SFTPD, respectively; an increased risk at 6 months was associated with rs1130866 of SFTPB and rs4715 of SFTPC, and increased and decreased risks at 12 months were associated with rs17886395 of SFTPA2 and rs2243639 of SFTPD, respectively; 3) in a two-SNP model, PRM susceptibility at both timepoints was associated with a number of intergenic interactions between SNPs of the studied SP genes. An increased risk at 12 months was associated with one intragenic (rs1965708 and rs113645 of SFTPA2) interaction; 4) in a three-SNP model, decreased and increased risks at 6 and 12 months, respectively, were associated with an interaction among rs1130866 of SFTPB, rs721917 of SFTPD, and rs1059046 of SFTPA2. A decreased risk at 6 months was associated with an interaction among the same SNPs of SFTPB and SFTPD and the rs1136450 of SFTPA1. The findings revealed that SNPs of all SFTPs appear to play a role in long-term outcomes of ARF survivors and may serve as markers for disease susceptibility.

Overview of cerebral cavernous malformations: comparison of treatment approaches

ObjectivesThe comparison of treatment efficacy for cerebral cavernous malformations (CCMs) has not yet been well researched.DesignPubMed, Cochrane Library, Science Direct, ISI Web of Science, Embase and additional sources were searched...

Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

BackgroundNeonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh.ResultsOut of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes.ConclusionBA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.

A role for insulin-like growth factor-1 in hippocampal plasticity following traumatic brain injury.

Traumatic brain injury (TBI) initiates a constellation of secondary injury cascades, leading to neuronal damage and dysfunction that is often beyond the scope of endogenous repair mechanisms. Cognitive deficits are among the most persistent morbidities resulting from TBI, necessitating a greater understanding of mechanisms of posttraumatic hippocampal damage and neuroplasticity and identification of therapies that improve recovery by enhancing repair pathways. Focusing here on hippocampal neuropathology associated with contusion-type TBIs, the impact of brain trauma on synaptic structure and function and the process of adult neurogenesis is discussed, reviewing initial patterns of damage as well as evidence for spontaneous recovery. A case is made that insulin-like growth factor-1 (IGF-1), a growth-promoting peptide synthesized in both the brain and the periphery, is well suited to augment neuroplasticity in the injured brain. Essential during brain development, multiple lines of evidence delineate roles in the adult brain for IGF-1 in the maintenance of synapses, regulation of neurotransmission, and modulation of forms of synaptic plasticity such as long-term potentiation. Further, IGF-1 enhances adult hippocampal neurogenesis though effects on proliferation and neuronal differentiation of neural progenitor cells and on dendritic growth of newly born neurons. Post-injury administration of IGF-1 has been effective in rodent models of TBI in improving learning and memory, attenuating death of mature hippocampal neurons and promoting neurogenesis, providing critical proof-of-concept data. More studies are needed to explore the effects of IGF-1-based therapies on synaptogenesis and synaptic plasticity following TBI and to optimize strategies in order to stimulate only appropriate, functional neuroplasticity.

Risk Factors for Late Persistent Fatigue After Chemoradiotherapy in Patients With Locally Advanced Cervical Cancer: An Analysis From the EMBRACE-I Study

This study aimed to evaluate patient- and treatment-related risk factors for late persistent fatigue within the prospective, multicenter EMBRACE-I study. Fatigue was prospectively assessed (Common Terminology Criteria for Adverse Events, version 3) at baseline and during regular follow up in 993 patients with locally advanced cervical cancer after treatment with chemoradiotherapy and magnetic resonance imaging-guided brachytherapy. Risk factors for baseline and late persistent fatigue were evaluated with multivariable logistic regression. Late persistent fatigue was defined when either grade ≥1 or ≥2 was scored in at least half of the follow ups. The median follow-up time was 57 months. Baseline fatigue grade ≥1/≥2 (35.8%/6.3%, respectively) was associated with preexisting comorbidities, World Health Organization performance status, being underweight, severe pain, and tumor volume. Late persistent grade ≥1/≥2 fatigue (36.3%/5.8%, respectively) was associated with patient-related factors (baseline fatigue, younger age, obesity) along with the size of irradiated volumes and the level of radiation doses from external beam radiation therapy (EBRT) and brachytherapy (EBRT: V43Gy, V57Gy; EBRT+brachytherapy: V60Gy equivalent dose in 2-Gy fractions). Large-volume lymph node (LN) boost increased the risk for late persistent fatigue grade ≥2 by 18% and 5% in patients with and without baseline fatigue, respectively, compared with no LN boost. The risk for late persistent fatigue grade ≥1 increased by 7% and 4% with V43Gy <2000 cm³ versus >3000 cm³ in patients with and without baseline fatigue, respectively. Late persistent grade ≥1 fatigue occurred in 13% of patients without late persistent organ-related symptoms (gastrointestinal, genitourinary, and vaginal) versus 34% to 43%, 50% to 58%, and 73% in patients suffering from persistent symptoms involving 1, 2, or 3 organs, respectively. Late persistent fatigue occurs in a considerable number of patients after chemoradiotherapy, and is associated with patient-related factors, the size of volumes irradiated to intermediate and high EBRT and brachytherapy doses, and other persistent organ-related morbidity. These findings support the importance of ongoing efforts to better tailor the target dose and reduce irradiation of healthy tissue without compromising target coverage, using highly conformal EBRT and brachytherapy techniques.

Guided Aspiration for Determining the Microbiological Aetiology of Aortic Vascular Graft and Endograft Infections

Open and endovascular aortic repair may be complicated by aortic vascular graft or endograft infection (VGEI). Confirming the microbiological aetiology is a key element in providing the best available treatment to patients with a VGEI. The primary aim of this study was to describe the technique of direct aneurysm sac guided aspiration (DASGA) in determining the microbiological aetiology in a cohort of patients with VGEIs, and to report its diagnostic value. This was a retrospective observational single centre study performed between the years 2011 to 2020 in Malmö, Sweden. Patients with a suspected aortic VGEI, where a DASGA was performed at the Vascular Centre, were included in the study. In total, 31 guided aspirations were performed in 27 patients (25 male [93%]; median age 77 years [range 57 - 82 years]). The combination of culture and 16S rRNA/18S rRNA gave a microbial aetiology in 25/31 (81%) DASGAs. Importantly, excluding three cases where infection was ruled out, this rate increases up to 89%. A polymicrobial aetiology was found in six (24 %) cases. The most common bacteria found were Cutibacterium spp. (n= 8) and Listeria monocytogenes (n= 4). In total, the dominant aetiology could be further characterised into normal gut flora (n= 12; 48%) or skin commensals (n= 8; 32%). No patients had persistent morbidity related to the DASGA. DASGA can be used successfully to determine the microbiological aetiology of open and endovascular graft infections. This method appears to be safe, with a high success rate for confirming the microbiological aetiology of VGEIs, particularly if standard culturing methods are combined with 16S rRNA/18S rRNA. Finding the causative microbial aetiology is crucial, and in the vast majority of cases translumbar puncture can be used without serious complications.

Neurosurgical management of petrous bone lesions: classification system and selection of surgical approaches.

Surgery of petrous bone lesions (PBLs) is challenging for neurosurgeons. Selection of the surgical approach is an important key for success. In this study, the authors present an anatomical classification for PBLs that has been used by our group for over the past 26years. The objective of this study is to investigate the benefits and applicability of this classification. Between 1994 and 2019, 117 patients treated for PBLs were retrospectively reviewed. Using the V3 and arcuate eminence as reference points, the petrous bone is segmented into 3 parts: petrous apex, rhomboid, and posterior. The pathological diagnoses, selection of the operative approach, and the extent of resection (EOR) were analyzed and correlated using this classification. This series included 22 facial nerve schwannomas (18.8%), 22 cholesterol granulomas (18.8%), 39 chordomas/chondrosarcomas (33.3%), 6 trigeminal schwannomas (5.1%), 13 epidermoids/dermoids (11.1%), and 15 other pathologies (12.8%). PBLs were most often involved with the petrous apex and rhomboid areas (46.2%). The extradural subtemporal approach (ESTA) was most frequently used (57.3%). Gross total resection was achieved in 58.4%. Symptomatic improvement occurred in 92 patients (78.6%). Our results demonstrated a correlation between this classification with each type of pathology (p < .001), selection of surgical approaches (p < 0.001), and EOR (p = 0.008). Chordoma/chondrosarcoma, redo operations, and lesions located medially were less likely to have total resection. Temporary complications occurred in 8 cases (6.8%), persistent morbidity in 5 cases (4.3%), and mortality in 1 case. In this study, we proposed a simple classification of PBLs. Using landmarks on the superior petrosal surface, the petrous bone is divided into 3 parts, apex, rhomboid, and posterior. Our results demonstrated that chordoma/chondrosarcoma, redo operations, and lesions involving the tip of the petrous apex or far medial locations were more difficult to achieve total resection. This classification could help surgeons understand surgical anatomy framework, predict possible structures at risk, and select the most appropriate approach for each patient.

Pulmonary Sequelae at 4 Months After COVID-19 Infection: A Single-Centre Experience of a COVID Follow-Up Service.

IntroductionAt the end of the first year of the COVID-19 pandemic, more than 78 million known survivors were recorded. The long-term pulmonary sequelae of COVID-19 remain unknown.MethodsWe performed a retrospective analysis of a post-COVID follow-up service to estimate the burden of persistent pulmonary morbidity in hospitalised COVID survivors.ResultsA total of 221 patients were followed-up: 44 intensive care unit (ICU) and 177 ward patients. Further investigations were planned as per British Thoracic Society Guidelines: For all ICU patients (n = 44) and for 38 of 177 (21%) ward-based patients who had persistent symptoms and/or persistent radiographic changes on CXR at their initial 8-week follow-up visit. In the ward-based cohort, statistically significant associations with persistent symptoms were being an ex- or current smoker, having pre-existing diabetes, and having a longer length of stay. In patients requiring further investigations, pulmonary function tests (PFTs; n = 67) at an average of 15 weeks post-discharge showed abnormalities in at least one PFT parameter in 79% (equating to 24% of the entire cohort). The most common abnormality was an abnormal diffusion capacity of carbon monoxide (TLCO), highest in the ICU cohort (64% ICU vs. 38% non-ICU). TLCO correlated negatively with length of stay and with maximum inspired FiO2 in the patient group as a whole. In ICU patients, TLCO correlated negatively with maximum inspired positive airway pressure. Computed tomography scans (n = 72) at an average of 18 weeks post-discharge showed evidence of persistent ground glass opacities in 44% and fibrosis in 21% (equating to 7% of the entire cohort).ConclusionOur data add to the growing evidence that there will be pulmonary sequelae in a proportion of COVID survivors, providing some insight into what may become a significant chronic global health problem.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01833-4.

PROPHYLACTIC VS. SYMPTOMATIC THIRD MOLAR REMOVAL: EFFECTS ON PATIENT POSTOPERATIVE MORBIDITY

The present study aimed to assess differences in postoperative morbidity between prophylactic and symptomatic third molar removals, and to assess the effect of age on the recovery of the patient. Patients admitted for third molar removal were prospectively followed up four times during treatment in context of the M3BE study. Data were collected through pre-, peri and postoperative surveys (days 3 and 10). Uni- and multivariable logistic regression was used to assess the probability of postoperative symptoms of discomfort on day 3 and day 10 according to several patient- and surgery-related predictive factors (age, gender, indication for removal, method of extraction, anesthesia and number of extracted maxillary and/or mandibular third molars). In total, 6010 patients with a mean age of 25.2 (± 11.2) underwent 6347 surgeries to have 15,357 third molars removed. Frequently observed symptoms of postoperative discomfort were pain, trismus and swelling, all of which were transient in nature with steep decreases from postoperative days 3 to 10. Increasing age was associated with an enhanced risk of persistent pain, trismus and swelling and a significantly higher risk of iatrogenic injury to the inferior alveolar nerve. Symptomatic indications for removal were more common in patients over age 25 years, but these pre-existing pathologies did not compromise the postoperative recovery process. Other factors related to postoperative morbidity were female gender, intraoperative osteotomy and the number of extractions. The results of this study suggest that there are convincing patient- and surgery-related factors that favor timely third molar removal, preferably before the age of 25, especially in order to avoid persistent morbidity and nerve complications.

Endocrine toxicities of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and inhibiting cytotoxic T lymphocyte antigen 4 (CTLA4) or PD1 and its ligand PDL1. ICIs, such as nivolumab, pembrolizumab and ipilimumab, are approved for the treatment of numerous and diverse cancer types, in various combination regimens, and are now an established cornerstone of cancer therapeutics. Toxicities induced by ICIs are autoimmune in nature and are referred to as immune-related adverse events (irAEs); these events can affect any organ system in an unpredictable fashion. Importantly, irAEs can manifest as endocrinopathies involving the thyroid (hypothyroidism or thyrotoxicosis), pituitary (hypophysitis), adrenal glands (adrenal insufficiency) and pancreas (diabetes mellitus). These events are a frequent source of acute and persistent morbidity in patients treated with ICIs and can even be fatal. Over the past few years, there has been a growing understanding of the underlying pathogenesis of irAEs that has led to the development of more effective management strategies. Herein, we review the current understanding of the pathobiology, clinical manifestations and treatment approaches to endocrine toxicities arising from ICIs.

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity.

Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, ‘biological hotspots’ (as distinct from ‘operational hotspots’) of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only persistently high infection intensities, but both “subtle” and severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host. We then take the situation of schistosomiasis mansoni within the Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot).

Pulmonary hypertension is an important co-morbidity in developmental lung diseases of infancy: Bronchopulmonary dysplasia and congenital diaphragmatic hernia.

Bronchopulmonary dysplasia (BPD) following preterm birth and congenital diaphragmatic hernia (CDH) are both forms of developmental lung disease that may result in persistent pulmonary and pulmonary vascular morbidity in childhood. The pulmonary vascular disease (PVD) which accompanies BPD and CDH is due to developmental abnormalities and ongoing perinatal insults. This may be accompanied by evidence of elevated right heart pressures and pulmonary vascular resistance, leading to diagnosis of pulmonary hypertension (PH). The development of PH in these conditions is associated with increased morbidity and mortality in the vulnerable BPD and CDH populations. We present a review of PVD pathogenesis and evaluation in BPD and CDH and discuss management of related sequelae of PH co-morbidity for affected infants.