The natural course of binge-eating disorder: findings from a prospective, community-based study of adults.

BACKGROUND: Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies. METHODS: Probands and relatives with current DSM-IV BED (n = 156) from a family study of BED ('baseline') were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints. RESULTS: Of participants with follow-up data (n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables. CONCLUSIONS: Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.

Age dependent effects of early intervention in borderline personality disorder in adolescents.

BACKGROUND: Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD. METHODS: N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up. RESULTS: Older adolescents presented with more BPD criteria (χ2(1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2(2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease. CONCLUSIONS: Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.

The natural course of idiopathic cervical dystonia.

Idiopathic cervical dystonia (ICD) is by far the largest subgroup of dystonia. Still, its natural course is largely unknown. We studied the natural course of 100 ICD patients from our botulinum toxin clinics (age at ICD onset 45.8 ± 13.5 years, female/male ratio 2.0) over a period of 17.5 ± 11.5 years with follow-ups during botulinum toxin therapy and with semi-structured interviews. Two courses of ICD could be distinguished by symptom development of more or less than 6 months. ICD-type 2 was less frequent (19% vs 81%, p < 0.001), had a more rapid onset (8.7 ± 8.0 weeks vs 3.8 ± 3.5 years), a higher remission rate (92% vs 5%, p < 0.001) and a higher prevalence of excessive psychological stress preceding ICD (63% vs 1%, p < 0.001). In both ICD-types, the plateau phase was non-progressive. Significant differences in patient age at ICD onset, latency and extent of remission, female/male ratio and prevalence of family history of dystonia could not be detected. ICD is a non-progressive disorder. ICD-type 1 represents the standard course. ICD-type 2 features rapid onset, preceding excessive psychological stress and a high remission rate. These findings will improve prognosis, treatment strategies and understanding of underlying disease mechanisms. They contradict the widespread fear of patients of a constant and continued decline of their condition. Excessive psychological stress may be an epigenetic factor triggering the manifestation of genetically predetermined dystonia.

Disease severity in subsequent pregnancies with RhD immunization: A nationwide cohort.

BACKGROUND AND OBJECTIVES: To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease. MATERIALS AND METHODS: Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD-positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD-positive child and thus after receiving anti-D at least twice (group A) or during the first pregnancy at risk for immunization (group B). RESULTS: Sixty-two RhD immunized women with a total of 150 RhD-positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD-positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non-intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody-dependent cell-mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD-positive child (group B), often before they had ever received anti-D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%). CONCLUSION: RhD-mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD-positive child are at highest risk of severe disease in the next pregnancy.

Naturalistic symptom trajectories of atypical anorexia nervosa, anorexia nervosa, and bulimia nervosa in a prospective cohort study of United States college students.

OBJECTIVE: Research on the natural course of symptoms of atypical anorexia nervosa (AN) relative to AN and bulimia nervosa (BN) is limited yet needed to inform nosology and improve understanding of atypical AN. This study aimed to 1) characterize trajectories of eating disorder and internalizing (anxiety, depression) symptoms in college students with and without a history of atypical AN, AN, and BN; and 2) compare sex and race/ethnicity distributions across groups. METHOD: United States college students who participated in Spit for Science™, a prospective cohort study, were classified as having a history of atypical AN (n = 125), AN (n = 160), BN (n = 617), or as non-eating-disorder controls (NCs, n = 5876). Generalized and linear mixed-effects models assessed group differences in eating and internalizing symptom trajectories, and logistic regression compared groups on sex and race/ethnicity distributions. RESULTS: Atypical AN participants demonstrated elevated eating disorder and internalizing symptoms compared to NCs during college, but less severe symptoms than AN and BN participants. Although all eating disorder groups showed signs of improvement in fasting and driven exercise, purging and depression remained elevated. Atypical AN participants showed increasing anxiety and stable binge-eating trajectories compared to AN and/or BN participants. The atypical AN group comprised significantly more people of color than the AN group. DISCUSSION: Findings underscore that atypical AN is a severe psychiatric disorder. As atypical AN may present as less severe than AN and BN and disproportionately affects people of color, clinicians should be mindful of biases that could delay diagnosis and care. PUBLIC SIGNIFICANCE: College students with histories of atypical AN, AN, and BN demonstrated improvements in fasting and driven exercise and stable purging and depression levels. Atypical AN students showed worsening anxiety and stable binge-eating trajectories compared to favorable changes among AN and BN students. A higher percentage of atypical AN (vs. AN) students were people of color. Findings may improve the detection of atypical AN in college students.

The long-term course and prognosis of postpartum depression: a retrospective longitudinal cohort study.

The purpose is to investigate the natural course and long-term prognosis of postpartum depression (PPD). In this retrospective longitudinal cohort study, mothers diagnosed as either suffering from PPD or without PPD were reassessed 5-8 years thereafter by a semi-structured interview and their charts were reviewed for past psychiatric illness prior to the index (initial) episode and for new-onset episodes in the following years. Present psychiatric state was also evaluated by interview and questionnaires. Sixty-five mothers with and 35 without past PPD underwent the full assessment. A total of 66.2% of mothers with past PPD had any axis I psychopathology before their index PPD episode, compared with only 8.6% in the non-PPD group (p < 0.001, φ = .55). Furthermore, 37.2% of the females who had a history of PPD and experienced subsequent childbirths during the follow-up years, developed at least one new episode of PPD. Throughout the 5 years subsequent to the index PPD episode, 42.5% of the PPD group compared with only 3.7% for the non-PPD group developed a new episode of depression (p < 0.001). Lastly, reported psychopathology was higher and functional level was significantly worse in the PPD group at the time of reassessment. Females who develop an episode of PPD show a high degree of subsequent psychopathology and unfavorable prognosis. Clinicians treating females for PPD should consider a longer treatment continuation phase in an effort to prevent further psychopathology and a closer follow-up program.

Acetabular coverage exerts minimal influence on femoral head collapse and the necessity for surgical intervention in patients with osteonecrosis of femoral head.

PURPOSE: The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse. METHODS: The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated. RESULTS: There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse. CONCLUSIONS: Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.

Time Course of Asymptomatic Stenosis in Multiple Lumbar Spinal Stenosis-Five-Year Results of Selective Decompression of Symptomatic Levels.

Background: In the diagnosis of lumbar spinal stenosis (LSS), finding stenosis with magnetic resonance imaging (MRI) does not always correlate with symptoms such as sciatica or intermittent claudication. We perform decompression surgery only for cases where the levels diagnosed from neurological findings are symptomatic, even if multiple stenoses are observed on MRI. The objective of this study was to examine the time course of asymptomatic stenosis in patients with LSS after they underwent decompression surgery for symptomatic stenosis. Materials and Methods: The participants in this study comprised 137 LSS patients who underwent single-level L4-5 decompression surgery from 2003 to 2013. The dural sac cross-sectional area at the L3-4 disc level was calculated based on preoperative MRI. A cross-sectional area less than 50 mm2 was defined as stenosis. The patients were grouped, according to additional spinal stenosis at the L3-4 level, into a double group (16 cases) with L3-4 stenosis, and a single group (121 cases) without L3-4 stenosis. Incidences of new-onset symptoms originating from L3-4 and additional L3-4-level surgery were examined. Results: Five years after surgery, 98 cases (72%) completed follow-up. During follow-up, 2 of 12 patients in the double group (16.7%) and 9 of 86 patients in the single group (10.5%) presented with new-onset symptoms originating from L3-4, showing no significant difference between groups. Additional L3-4 surgery was performed for one patient (8.3%) in the double group and three patients (3.5%) in the single group; again, no significant difference was shown. Conclusion: Patients with asymptomatic L3-4 stenosis on preoperative MRI were not prone to develop new symptoms or need additional L3-4-level surgery within 5 years after surgery when compared to patients without preoperative L3-4 stenosis. These results indicate that prophylactic decompression for asymptomatic levels is unnecessary.

Management of circumscribed choroidal hemangioma at a tertiary care center.

PURPOSE: To review long-term outcomes of circumscribed choroidal hemangioma (CCH). METHODS: Hospital charts of all CCH cases diagnosed from 2008 to 2019 were retrospectively reviewed. RESULTS: All 172 patients were managed with either observation, transpupillary thermotherapy, argon laser photocoagulation, photodynamic therapy, plaque brachytherapy or stereotactic radiosurgery. The most common 3 modes of management were clinical observation (30.2%), transpupillary thermotherapy (52.9%) and argon laser photocoagulation (8.7%). Median follow-up time was 10 months (range: 3, 160). Anatomical outcomes were stable in 87.1% of observation group and improved in 60.5% of thermotherapy group. Quantified optical coherence tomography angiography findings showed statistical differences in vascular and perfusion densities in fellow eyes of hemangioma patients. CONCLUSION: Circumscribed choroidal hemangioma can be treated in various ways. Transpupillary thermotherapy is an anatomically effective treatment in selected cases. The diagnosis of CCH may have vascular implications in fellow eyes of the patients.

Deconstructing the heterogeneity of alcohol use disorder: lifetime comorbid non-alcohol substance use disorder as a distinct behavioral phenotype?

BACKGROUND: Alcohol use disorder (AUD) is an etiologically and clinically heterogeneous condition. Accumulating evidence suggests that persons with lifetime histories of comorbid AUD and non-alcohol substance use disorder (DRUG) constitute an important subgroup of AUD. This study evaluated the distinctiveness of the comorbid AUD/DRUG behavioral phenotype in a community sample with respect to risk factors, AUD course features, and outcome variables assessed at age 30. Contrast groups included persons with histories of AUD only, DRUG only, and neither AUD nor DRUG. METHODS: This research utilized a prospective study design with an age-based cohort (n = 732). Participants completed four comprehensive diagnostic evaluations during the high-risk periods of adolescence, emerging adulthood, and young adulthood. RESULTS: The comorbid AUD/DRUG group was distinguished from the AUD only group by risk factors, AUD course features, and outcomes. Group differences in outcomes were also explained by overall substance use disorder (SUD) severity. Persons with AUD/DRUG comorbidity were indistinguishable from those with DRUG only histories with respect to risk factors and outcomes but demonstrated greater overall SUD severity. Persons with AUD only were indistinguishable from those with neither AUD nor DRUG histories in risk factor endorsements and were mostly similar in outcomes. CONCLUSIONS: Findings collectively suggest that young adults with histories of AUD only and those with comorbid AUD/DRUG are drawn from dissimilar populations. Similarities between the AUD only group with those absent AUD or DRUG histories are likely related to the former group's developmentally limited AUD course accompanied by relatively few or short-lived alcohol-related problems.

Central nervous system cavernous malformations: cross-sectional study assessing rebleeding risk after a second haemorrhage.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 5-year risk of a third bleeding event in cavernous malformations (CMs) of the central nervous system. METHODS: Patients with cerebral or spinal CMs treated between 2003 and 2021 were screened using our institutional database. Patients with a complete magnetic resonance imaging dataset, clinical baseline characteristics, and history of two bleeding events were included. Patients who underwent surgical CM removal were excluded. Neurological functional status was obtained using the modified Rankin Scale score at the second and third bleeding. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for a third haemorrhage. RESULTS: Forty-two patients were included. Cox regression analysis adjusted for age and sex did not identify risk factors for a third haemorrhage. 37% of patients experienced neurological deterioration after the third haemorrhage (p = 0.019). The cumulative 5-year risk of a third bleeding was 66.7% (95% confidence interval [CI] 50.4%-80%) for the whole cohort, 65.9% (95% CI 49.3%-79.5%) for patients with bleeding at initial diagnosis, 72.7% (95% CI 39.3%-92.7%) for patients with a developmental venous anomaly, 76.9% (95% CI 55.9%-90.3%) for patients with CM localization to the brainstem and 75% (95% CI 50.6%-90.4%) for patients suffering from familial CM disease. CONCLUSIONS: During an untreated 5-year follow-up after a second haemorrhage, a significantly increased risk of a third haemorrhage compared to the known risk of a first and second bleeding event was identified. The third bleeding was significantly associated with neurological deterioration. These findings may justify a surgical treatment after a second bleeding event.

Modifiable vascular risk factors in patients with cerebral and spinal cavernous malformations: a complete 10-year follow-up study.

BACKGROUND AND PURPOSE: The aim was to investigate the effect of modifiable vascular risk factors on the risk of first and recurrent bleeding for patients with a cavernous malformation (CM) of the central nervous system (CNS) over a 10-year period. METHODS: A retrospective review of our CM institutional database was performed spanning from 2003 to 2021. The inclusion criteria were non-missing serial magnetic resonance imaging studies and clinical baseline metrics such as vascular risk factors. The exclusion criteria were patients who underwent surgical CM removal and patients with less than a decade of follow-up. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative risk (10 years) of hemorrhage. RESULTS: Eighty-nine patients with a CM of the CNS were included. Our results showed a non-significant increased risk of hemorrhage during 10 years of follow-up in patients using nicotine (hazard ratio 2.11, 95% confidence interval 0.86-5.21) and in patients with diabetes (hazard ratio 3.25, 95% confidence interval 0.71-14.81). For the presence of modifiable vascular risk factors at study baseline different cumulative 10-year risks of bleeding were observed: arterial hypertension 42.9% (18.8%-70.4%); diabetes 66.7% (12.5%-98.2%); hyperlipidemia 30% (8.1%-64.6%); active nicotine abuse 50% (24.1%-76%); and obesity 22.2% (4%-59.8%). Overall cumulative (10-year) hemorrhage risk was 30.3% (21.3%-41.1%). CONCLUSIONS: The probability of hemorrhage in untreated CNS CM patients increases progressively within a decade of follow-up. None of the modifiable vascular risk factors showed strong indication for an influence on hemorrhage risk, but our findings may suggest a more aggressive course in patients with active nicotine abuse or suffering from diabetes.

Natural Course of Common Bile Duct Microlithiasis.

BACKGROUND: Common bile duct microlithiasis (CBDM) with a diameter of ≤ 3 mm can pass spontaneously without causing any symptoms, but in some cases, it can also cause severe cholangitis and pancreatitis. The optimal strategy for managing CBDM is yet to be determined. METHODS: Data of 154 patients with CBDM were collected and divided into two groups: with endoscopic retrograde cholangiopancreatography (with ERCP, n = 82) and without ERCP (n = 72). Clinical outcomes, including the incidence of unfavorable outcomes (UOs), such as cholangitis and pancreatitis, were observed and compared between the two groups. RESULTS: The incidence of UOs was significantly lower in the ERCP group than in the without ERCP group (3.7% vs. 23.6%, respectively, p < 0.001). Moreover, the total number of readmissions was also lower in the ERCP group than in the without ERCP group (p < 0.001). A multivariate analysis adjusted for age, sex, and the American Society of Anesthesiologists (ASA) class revealed that endoscopic sphincterotomy (EST) and cholecystectomy were associated with a lower risk of UOs. CONCLUSION: The high rate of UOs in CBDM patients without ERCP suggests that its natural clinical course may not be as favorable as previously suggested. This finding implies that efforts should be made to clear the bile ducts.

The Role of the Natural Course in Causal Analysis.

The average causal effect compares counterfactual outcomes if everyone had been exposed versus if everyone had been unexposed, which can be an unrealistic contrast. Alternatively, we can target effects that compare counterfactual outcomes against the factual outcomes observed in the sample (i.e., we can compare against the natural course). Here, we demonstrate how the natural course can be estimated and used in causal analyses for model validation and effect estimation. Our example is an analysis assessing the impact of taking aspirin on pregnancy, 26 weeks after randomization, in the Effects of Aspirin in Gestation and Reproduction trial (United States, 2006-2012). To validate our models, we estimated the natural course using g-computation and then compared that against the observed incidence of pregnancy. We observed good agreement between the observed and model-based natural courses. We then estimated an effect that compared the natural course against the scenario in which participants assigned to aspirin always complied. If participants had always complied, there would have been 5.0 (95% confidence interval: 2.2, 7.8) more pregnancies per 100 women than was observed. It is good practice to estimate the natural course for model validation when using parametric models, but whether one should estimate a natural course contrast depends on the underlying research questions.

Can Interferon Therapy Change the Natural Course of Hepatitis Delta Infection?: a Clinical and Pathological Study.

Chronic delta hepatitis (CDH) has a worse outcome than other types of viral hepatitis. High-dose, long-term alpha interferon (IFN-α) is the approved treatment and may ameliorate the course of infection. We evaluated long-term histological outcomes of CDH patients treated with IFN-α. Patients with histologically proved noncirrhotic CDH who were treated with high-dose IFN-α for at least 1 year were classified as cirrhotic or noncirrhotic at the end of treatment. Noncirrhotic patients also had posttreatment liver biopsies. Patients were designated histologically responsive or nonresponsive on the basis of fibrosis status. Histological, virological, and biochemical courses were analyzed. Forty-eight patients were treated with IFN-α (conventional and/or pegylated) for a median of 24 months with a posttreatment follow-up of 5 years. During the follow-up, cirrhosis developed in 24 patients, 5 of whom were decompensated. There was no difference between pre- and posttreatment fibrosis scores for 24 noncirrhotic patients at the end of follow-up. Among patients, 13% (n = 6) had decreased, 21% (n = 10) had steady, and 16% (n = 8) had increased fibrosis scores. Persistent viral response (PVR) was achieved in 16 patients (33%). Twenty percent of the entire group was histologically responsive (decreasing or steady fibrosis scores with improved necroinflammatory scores), while nearly 80% had histological progression/cirrhosis. PVR was significantly associated with histological response. The long-term natural course of patients who were treated with high dose IFN-α for at least 1 year was evaluated clinically and histologically. Despite the association of PVR with histological response, IFN-α treatment did not change the natural course of CDH; clinical and histological progression continued in two-thirds of the cases despite treatment.

Active expectancy as alternative to treatment for cervical intraepithelial neoplasia grade 2 in women aged 25 to 30 years: ExCIN2-a prospective clinical multicenter cohort study.

BACKGROUND: The management of cervical intraepithelial neoplasia grade 2 is a clinical dilemma. Cervical intraepithelial neoplasia grade 3 is considered a cancer precursor and is always treated with excision. Most of the cervical intraepithelial neoplasia grade 1 cases regress spontaneously, and it is internationally mostly monitored with expectant management. Surgical treatment of cervical intraepithelial neoplasia entails increased risk of preterm birth in future pregnancies. Cervical intraepithelial neoplasia grade 2 in women aged under 25 years is quite well-studied; the regression rate is high and the cervical cancer risk is low. Cervical intraepithelial neoplasia grade 2 in women aged 25 years and above, in whom the risk of occult cancer is higher, has been less studied. OBJECTIVE: This study aimed to evaluate the natural course, over 2 years, of untreated cervical intraepithelial neoplasia grade 2 in women aged 25 to 30 years and its association with human papillomavirus 16. STUDY DESIGN: The study was conducted as a prospective longitudinal multicenter clinical study during February 2017 to June 2021 at 5 colposcopy clinics managing referrals after abnormal cervical screening in Region Västra Götaland, Sweden. The per protocol group comprised 127 women, aged 25 to 30 years, with fully visible squamocolumnar junction and histologically verified cervical intraepithelial neoplasia grade 2. The patients were followed up for 2 years with colposcopy, cytology, human papillomavirus tests, and at least 2 cervical biopsies every 6 months until progression or regression. The main outcome measures were the rates of regression of cervical intraepithelial neoplasia grade 2 at 6, 12, 18, and 24 months in cases with human papillomavirus 16 and those without human papillomavirus 16. The secondary outcomes were persistence and progression. RESULTS: In the per protocol analysis, partial or total regression during the 2-year period was found in 72% of patients (95% confidence interval, 63-79). In patients with human papillomavirus 16, the regression rate was 51% (95% confidence interval, 36-66) and the progression rate was 47% (95% confidence interval, 32-62). In the human papillomavirus-non-16 group, 83% (95% confidence interval, 73-90) regressed and 16% (95% confidence interval, 9-26) progressed. Most of the regression and progression in both the groups occurred within 15 months. The difference in regression between human papillomavirus 16 and human papillomavirus-non-16 cases was statistically significant (P value=.0001), as was the difference in progression (P=.0002). CONCLUSION: The regression rate of cervical intraepithelial neoplasia grade 2 is high, and human papillomavirus 16 is a strong determinant of the natural course. Patients aged 25 to 30 years with a fully visible squamocolumnar junction and without human papillomavirus 16 should generally be recommended active surveillance for 15 months, whereas immediate treatment should be considered in cases with human papillomavirus 16.

Multiple cerebral cavernous malformations: Clinical course of confirmed, assumed and non-familial disease.

BACKGROUND AND PURPOSE: Analyze and compare the natural course of confirmed familial cerebral cavernous malformation (FCCM), assumed FCCM and non-familial multiple cerebral cavernous malformation (CCM) disease over a 5-year period. METHODS: Our institutional database was screened for patients with CCM admitted between 2003 and 2020. Patients with complete magnetic resonance imaging dataset, evidence of multiple CCM, clinical baseline characteristics, and follow-up examination were included. Patients were separated into confirmed familial cases, assumed familial cases or non-familial multiple cavernous malformations. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for hemorrhage and recurrent hemorrhage. RESULTS: A total of 238 patients with multiple CCM were analyzed; 90 individuals had a confirmed FCCM disease, 115 an assumed FCCM, and 33 were allocated to the non-FCCM group. Univariate Cox regression analysis identified intracerebral hemorrhage (ICH) as mode of presentation (p = 0.001) as a predictor for occurrence of recurrent hemorrhage during the 5-year follow-up (FU). The cumulative 5-year risk of (re)bleeding was 21.6% for the entire cohort, 30.7% for patients with ICH at diagnosis, 22.1% for those patients with a confirmed diagnosis of FCCM, 23.5% for those with an assumed FCCM, and 21% for the non-FCCM cases. CONCLUSIONS: FCCM patients with ICH at diagnosis are prone to develop rebleeding. During untreated 5-year FU, FCCM patients and patients with sporadic multiple CCM reveal an almost equal susceptibility for (re)hemorrhage. Moreover, confirmed, assumed and non-FCCM patients showed an equal cumulative 5-year risk of symptomatic ICH. The probability of hemorrhage tends to increase over time, particularly in cases with ICH at presentation.

Natural Course of Optic Disc Pit Maculopathy: An Optical Coherence Tomography Study.

PURPOSE: The aim of this study was to analyze the impact of OCT characteristics on the natural course of optic disc pit maculopathy (ODP-M). METHODS: This was a single-center, retrospective, observational case series. Patients with ODP-M were included in the study. Baseline demographic characteristics, central macular thickness (CMT), IPP, subretinal fluid (SRF), subretinal precipitations, outer retinal fluid (ORF), and outer retinal layer hole were evaluated. The changes in the OCT characteristics were analyzed with respect to the best-corrected visual acuity (BCVA) from baseline to the last visit. RESULTS: Twenty-two eyes of 22 patients were evaluated with a mean follow-up time of 37.6 (median 22) months. The mean BCVA was 0.31 logMAR at baseline and 0.28 logMAR at the final visit (p = 0.521). Baseline BCVA was significantly related to CMT (ß coefficient 0.001, p = 0.002). Mean BCVA increased in 7 patients (group 1), remained stable in nine (group 2), and decreased (group 3) in 6 patients. No significant difference was found between the groups regarding the baseline BCVA, CMT, and extent of retinal fluid. In patients with subretinal deposits, BCVA remained stable in 3 patients and worsened in one. ORF was recorded in all patients. In patients with SRF, the mean change of BCVA during follow-up differed significantly, depending on the presence (0.07 logMAR) or absence (-0.125 logMAR) of SRF (p = 0.019). CONCLUSION: Among the OCT characteristics, SRF was a negative prognostic factor in ODP-M. Most ODP-M patients showed improved or stable vision over 3 years of follow-up. Therefore, observation may be considered in patients with reasonable vision and without SRF even when they present with remarkable OCT findings.

Safety of early posterior fusion surgery without endovascular embolization for asymptomatic vertebral artery occlusion associated with cervical spine trauma.

PURPOSE: Vertebral artery occlusion (VAO) is an increasingly recognized complication of cervical spine trauma. However, the management strategy of VAO remains heavily debated. Therefore, the aim of this retrospective study was to investigate the safety of early fusion surgery for traumatic VAO. METHODS: This study included a total of 241 patients (average age 64.7 years; 201 men) who underwent early surgical treatment for acute cervical spine injury between 2012 and 2019. The incidence of VAO, cerebral infarction rates, the recanalization rates, and cerebral thromboembolism after recanalization were retrospectively analyzed. RESULTS: VAO occurred in 22 patients (9.1%). Of the 22 patients with VAO, radiographic cerebral infarction was detected in 4 patients (21.1%) at initial evaluation, including 1 symptomatic medullar infarction (4.5%) and 3 asymptomatic cerebrum infarctions. A patient who experienced right medullar infarction showed no progression of the neurologic damage. Follow-up imaging revealed that the VAOs of 9 patients (40.9%) were recanalized, and the recanalization did not correlate with clinical adverse outcomes. The arteries of the remaining 13 (59.1%) patients remained occluded and clinically silent until the final follow-up (mean final follow-up 33.0 months). CONCLUSION: Despite the lack of a concurrent control group with preoperative antiplatelet therapy or endovascular embolization for VAO, our results showed low symptomatic stroke rate (4.5%), high recanalization rate (40.9%), and low mortality rate (0%). Therefore, we believe that the indication for early stabilization surgery as management strategy of asymptomatic VAO might be one of the safe and effective treatment options for prevention of symptomatic cerebral infarction.

Natural Course of Fetal Hyaloid Artery: SlowflowHD Longitudinal Study.

OBJECTIVE: To assess the natural course of the fetal hyaloid artery (FHA) using SlowflowHD during pregnancy. METHODS: One-hundred and eighteen normal fetuses were studied longitudinally using SlowflowHD to assess the natural course of FHA at 18-21 + 6, 28-31 + 6, and after 35 weeks of gestation. Blood flow of FHA with/without its branches (BF) was evaluated using SlowflowHD, and the band of FHA without blood flow (Band) was identified in each gestational period. The natural course of FHA was classified into six types: Type A, not detected (ND) in each gestational period; Type B, Band at 18-21 + 6 weeks; Type C, Band at 18-21 + 6 and 28-31 + 6 weeks; Type D, BF at 18-21 + 6 weeks; Type E, BF at 18-21 + 6 weeks and Band at 28-31 + 6 weeks; Type F, BF at 18-21 + 6 and 28-31 + 6 weeks. RESULTS: BF, Band, and ND were 83.5, 15.5, and 1.0% at 18-21 + 6 weeks, 8.8, 15.5, and 75.7% at 28-31 + 6 weeks, and 0, 0, and 100% after 35 weeks, respectively. Type A was 1.0%, Type B was 13.6%, Type C was 1.9%, Type D was 61.2%, Type E was 13.6%, and Type F was 8.7%. CONCLUSIONS: The presence of FHA blood flow before 30 weeks of gestation should be regarded as a physiologic phenomenon in normal fetuses.