The optimal treatment algorithm for patients with degenerative lumbar spondylolisthesis has not been clarified. Part of the reason for this is that the natural history of degenerative spondylolisthesis (DS) has not been sufficiently studied. Comprehension of the natural history is essential for surgical decision making. We aimed to determine 1) the proportion of patients that develop de novo DS during follow-up; and 2) the proportion of patients with progression of preexistent DS by conducting a systematic review and meta-analysis of the literature.
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Ovid, EMBASE, and the Cochrane Library were searched from their inception through April 2022. Demographic values of the study populations, grade of slip, rate of slippage before and after the follow-up period, and percentage of patients with slip in the populations at baseline and after follow-up were the extracted parameters.
Of the 1909 screened records, eventually 10 studies were included. Of these studies, 5 reported the development of de novo DS and 9 reported on the progression of preexistent DS. Proportions of patients developing de novo DS ranged from 12% to 20% over a period ranging from 4 to 25 years. The proportion of patients with progression of DS ranged from 12% to 34% over a period ranging from 4 to 25 years.
Systematic review and metanalysis of DS on the basis of radiologic parameters revealed both an increasing incidence over time and an increasing progression of the slip rate in up to a third of the patients older than 25 years, which is important for counseling patients and surgical decision making. Importantly, two thirds of patients did not experience slip progression.

The objective of this systematic review and meta-analysis is to determine whether nocturnal blood pressure fall, expressed by dipping patterns according to ambulatory blood pressure monitoring (ABPM), is a risk factor for cardiovascular events (CVEs) in untreated hypertensives. Α thorough systematic literature search at MEDLINE, Embase, Cochrane Library, and gray literature was conducted through March 2020. Two reviewers screened studies and assessed dipping patterns of untreated hypertensives using ABPM with a follow-up >6 months. Newcastle-Ottawa scale was used for risk of bias assessment. We initially identified 463 reports; of which, seven cohort studies were eligible for meta-analysis enrolling 10 438 untreated hypertensives. Untreated patients classified as dippers at baseline (n = 7081) had significant lower risk of CVEs and total mortality compared to non-dippers (n = 3,357) [RR = 0.67, 95% CI (0.49, 0.92); RR = 0.71, 95% CI (0.59, 0.86)]. However, when patients were further classified into four dipping groups, only reverse dippers, yet not extreme dippers or non-dippers, were at increased risk for CVEs compared to dippers [RR = 0.47, 95% CI (0.33, 0.66)]. Likewise, only reverse dippers had a higher stroke risk than dippers [RR = 0.39, 95% CI (0.22, 0.72)]. When compared with the whole group of dippers (including extreme dippers), non-dipping alone (excluding reverse dipping) was not a significant risk factor for CVEs [RR = 0.84, 95% CI (0.61, 1.16)] or total mortality [RR = 0.84, 95% CI (0.61, 1.16); RR = 0.78, 95% CI (0.53, 1.13), respectively]. Untreated hypertensives may benefit more from the evaluation of reverse dipping rather than the non-dipping phenomenon in general.

Comparing the course of antipsychotic-naïve psychosis in low- and middle-income countries (LMIC) may help to illuminate core pathophysiologies associated with this condition. Previous reviews-primarily from high-income countries (HIC)-identified cognitive deficits in antipsychotic-naïve, first-episode psychosis, but did not examine whether individuals with psychosis with longer duration of untreated psychosis (DUP > 5 years) were included, nor whether LMIC were broadly represented.
A comprehensive search of PUBMED from January 2002-August 2018 identified 36 studies that compared cognitive functioning in antipsychotic-naïve individuals with psychosis (IWP) and healthy controls, 20 from HIC and 16 from LMIC.
A key gap was identified in that LMIC study samples were primarily shorter DUP (<5 years) and were primarily conducted in urban China. Most studies matched cases and controls for age and gender but only 9 (24%) had sufficient statistical power for cognitive comparisons. Compared with healthy controls, performance of antipsychotic-naïve IWP was significantly worse in 81.3% (230/283) of different tests of cognitive domains assessed (90.1% in LMIC [118/131] and 73.7% [112/152] in HIC).
Most LMIC studies of cognition in antipsychotic-naïve IWP adopted standardized procedures and, like HIC studies, found broad-based impairments in cognitive functioning. However, these LMIC studies were often underpowered and primarily included samples typical of HIC: primarily male, young-adult, high-school educated IWP, in their first episode of illness with relatively short DUP (<5 years). To enhance understanding of the long-term natural course of cognitive impairments in untreated psychosis, future studies from LMIC should recruit community-dwelling IWP from rural areas where DUP may be longer.

Obesity is up to 4 times higher in patients with schizophrenia than in the general population. However, the link between obesity and schizophrenia in the absence of antipsychotic use is unclear. Therefore, we aimed to examine differences in obesity measures (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) in antipsychotic-naive and minimally treated (up to 2 weeks of lifetime antipsychotic exposure) patients with psychosis compared to healthy controls (HCs).
A systematic search was conducted using Ovid Medline®, PsycINFO, and Embase. Standardized mean differences (SMDs) in obesity measures between groups were calculated. Separate sensitivity analyses were performed to examine the effects of age, sex, and ethnicity; antipsychotic exposure; and schizophrenia-related psychosis on SMDs.
A total of 23 studies were included in the meta-analysis (BMI = 23, WC = 9, WHR = 5). BMI was lower (SMD = -0.19, 95% CI = -0.34 to -0.05, P = 0.009) and WHR was elevated (SMD = 0.34, 95% CI = 0.14 to 0.55, P = 0.001) in patients. These differences remained after analyses were restricted to patients matched with HCs for age, sex, and ethnicity; to antipsychotic-naive patients; and to patients with schizophrenia-related diagnoses.
Differences in BMI and WHR were observed in never and minimally treated patients with psychosis compared to HCs. Future research is warranted to understand these alterations in the context of body fat biomarkers and neuropathology of psychiatric disorders, independent of the effects of antipsychotics.

Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients.
To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ≥1200 μmol/l; and 3) IQ ≥80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers.
In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms.
Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.

Studies using proton magnetic resonance spectroscopy (1H-MRS) have reported altered neurometabolite levels in patients with schizophrenia. However, results are possibly confounded by the influence of antipsychotic (AP). Thus, this meta-analysis aimed to examine neurometabolite levels in AP-naïve/free patients with schizophrenia.
A literature search was conducted using Embase, Medline, and PsycINFO to identify studies that compared neurometabolite levels in AP-naïve/free patients with schizophrenia to healthy controls (HCs). Eight neurometabolites (glutamate, glutamine, glutamate + glutamine, N-acetylaspartate [NAA], choline, creatine, myo-inositol, and γ-Aminobutyric acid [GABA]) and seven regions of interest (ROI; medial prefrontal cortex, dorsolateral prefrontal cortex, frontal white matter, occipital lobe, basal ganglia, hippocampus/medial temporal lobe, and thalamus) were examined.
Twenty-one studies (N = 1281) were included in the analysis. The results showed lower thalamic NAA levels (3 studies, n = 174, effect size = -0.56, P = 0.0005) in the patient group. No group differences were identified for other neurometabolites.
Our findings suggest that impaired neuronal integrity in the thalamus may be a potential trait maker in the early stages of schizophrenia.

BACKGROUND: The use of chemotherapy in advanced metastatic breast cancer remains a subject of controversy. The thought of MicKinnon et al (early 1950s) that the course of breast cancer was unaffected by chemotherapy has been refuted by results of treatment in the developed countries. The poor result of treatment in developing centres still compares with prechemotherapy era. Consequently, The McKinnon\'s thought may still lurk. We compared the survival of chemotherapy treated with chemotherapy untreated cancer of breast patients.
METHODS: Records of breast cancer patients who presented and died between January 2010 and May 2014 were reviewed. The primary outcome was overall survival. Records of patients that received chemotherapy with or without other tumor directed specific therapy were compared with records of patients who did not receive any tumor directed therapy.
RESULTS: Thirty-one patients received chemotherapy while 25 patients did not. All were females, more than 90% were of the patients had advanced or metastatic disease. Treatments were not biologically directed and treatment plans were largely compromised and suboptimal. The overall mean survival was 19.2 ±9.2 months, and the median duration was 17.5 months(range 6-44months). The overall survival was not statistically different between the two groups (p= 0.230, unequal variance assumed). The objective of using neoadjuvant chemotherapy for fungating lesions was not achieved.
CONCLUSIONS: In advanced and metastatic breast cancer, outcomes of patients who receive suboptimal regimen of cytotoxic chemotherapy do not differ from chemotherapy untreated patients.