Category: Nevin Manimala

Mult Scler Relat Disord. 2023 Mar 21;73:104627. doi: 10.1016/j.msard.2023.104627. Online ahead of print.

ABSTRACT

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder.

OBJECTIVES: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD.

METHODS: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to “genetic” and “NMOSD” were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics.

RESULTS: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03.

CONCLUSION: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

PMID:37015139 | DOI:10.1016/j.msard.2023.104627

J Nerv Ment Dis. 2023 Apr 4. doi: 10.1097/NMD.0000000000001645. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are the two most prevalent neurodevelopmental disorders affecting communication and behavior. The co-occurrence of these conditions is probable and can contribute to several challenges in adaptive functioning and academic achievement.In this cross-sectional study, 168 Iranian medical students (107 female, 61 male) studying at Tehran University of Medical Sciences in 2021 were enrolled. We administered the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) and Adult ADHD Self-Report Scale (ASRS) questionnaires online to assess different symptoms of ASD and ADHD in our sample. In this study, the RAADS-R was translated into Persian and validated for the first time in Iran.The correlation tests demonstrated a significant association between the total score and different subscales’ scores of the RAADS-R and the total score and the two subscales’ scores of the ASRS questionnaire (p < 0.001, 0.27 < Spearman correlation coefficient < 0.51). This study also illustrated a high prevalence of ASD and ADHD symptoms among the participants. Moreover, male respondents had a significantly higher prevalence of ASD symptoms (57.3% in males vs. 28.03% in females, p < 0.001).This study indicated that the distinct impairments in behavior and cognition attributed to ASD and ADHD could be common manifestations in medical students. Given that the co-occurrence of these disorders may lead to significant challenges in their professional life, the early diagnosis and subsequent support for medical students with co-occurring expressions of ASD and ADHD could be extremely helpful, as it could indirectly improve the medical services provided to patients by future physicians, leading to an improvement in public health.

PMID:37015108 | DOI:10.1097/NMD.0000000000001645

Hum Reprod. 2023 Apr 4:dead053. doi: 10.1093/humrep/dead053. Online ahead of print.

ABSTRACT

STUDY QUESTION: What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)?

SUMMARY ANSWER: Excess body fat, even during childhood/adolescence, and metabolic parameters, suggestive of hyperinsulinaemia/insulin resistance, significantly impact the risk of PCOS in a linear fashion.

WHAT IS KNOWN ALREADY: Observational and Mendelian randomization (MR) data have demonstrated an association between adulthood overweight/obesity and development of PCOS. However, the contribution of body composition in childhood/adolescence to incident PCOS is unclear, as is the influence of childhood overweight/obesity.

STUDY DESIGN, SIZE, DURATION: We conducted a systematic review and meta-analysis and integrated our results with a previously published systematic review. Two blinded investigators screened abstracts published between November 2010 and May 2021. Furthermore, we incorporated summary statistics from genome-wide association study (GWAS) data in subjects of European ancestry. Adult overweight was defined as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2; in Asian subjects, overweight was defined as BMI ≥ 23 kg/m2 and obesity as BMI ≥ 25 kg/m2.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We utilized meta-analysis and MR together to allow synthesis of genetic and observational data. For the systematic review, the search revealed 71 studies, of which 63 were included in meta-analysis by calculating odds ratios (ORs) using the random-effects model. Furthermore, we conducted a two-sample MR study of GWAS data to determine the impact of childhood and adult body size (defined categorically by BMI and childhood body size proportions), abnormal body composition and metabolic parameters (higher fasting serum insulin or lower sex hormone-binding globulin (SHBG) concentration) on the odds of incident PCOS via the inverse-variance weighted method.

MAIN RESULTS AND THE ROLE OF CHANCE: Significant associations were shown between body composition and PCOS incidence. From the systematic review/meta-analysis, women with overweight (OR 3.80, 2.87-5.03), obesity (OR 4.99, 3.74-6.67), and central obesity (OR 2.93, 2.08-4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity, the PCOS odds were greater than for adults. From MR, for every standard deviation increase in BMI (4.8 kg/m2), the odds of PCOS increased by 2.76 (2.27-3.35). Childhood body size had an independent effect on PCOS odds after adjusting for adult body size (OR: 2.56, 1.57-4.20). Genetically determined body fat percentage (OR 3.05, 2.24-4.15), whole body fat mass (OR 2.53, 2.04-3.14), fasting serum insulin (OR 6.98, 2.02-24.13), and SHBG concentration (OR 0.74, 0.64-0.87) were all significantly associated with PCOS in a linear relation.

LIMITATIONS, REASONS FOR CAUTION: The meta-analysis included studies which were cross-sectional and retrospective, limiting our ability to determine causality. MR was limited by interrogating subjects only of European ancestry and including cases classified by either self-diagnosis or diagnostic criteria.

WIDER IMPLICATIONS OF THE FINDINGS: Our study demonstrates for the first time a critical role of the impact of excess childhood/adolescent adiposity on the pathophysiology of adult PCOS. Our results, driven by genetically determined childhood/adolescent body composition, higher BMI, hyperinsulinaemia, and lower SHBG, clearly favour obesity driving the metabolic, but not reproductive, PCOS phenotype. Overall, effective weight maintenance, even from the early years, is likely to reduce the risk of this reproductive endocrine disorder.

STUDY FUNDING/COMPETING INTEREST(S): S.S.Z. was funded by a National Institute for Health and Care Research (NIHR) Academic Clinical Lectureship. U.A. is chair of the NIHR Steering Committee Trial-CASSANDRA-DN. No other authors declare any sources of funding or relevant conflicts of interest. The authors declare that the research was conducted in the absence of any commercial or financial relations that could be construed as a potential conflict of interest.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37015099 | DOI:10.1093/humrep/dead053

Clin Chem Lab Med. 2023 Apr 6. doi: 10.1515/cclm-2022-1085. Online ahead of print.

ABSTRACT

OBJECTIVES: Human blood gas stability data is limited to small sample sizes and questionable statistical techniques. We sought to determine the stability of blood gases under room temperature and slushed iced conditions in patients using survival analyses.

METHODS: Whole blood samples from ∼200 patients were stored in plastic syringes and kept at room temperature (22-24 °C) or in slushed ice (0.1-0.2 °C) before analysis. Arterial and venous pO₂ (15-150 mmHg), pCO₂ (16-72 mmHg), pH (6.73-7.52), and the CO-oximetry panel [total hemoglobin (5.4-19.3 g/dL), percentages of oxyhemoglobin (O₂Hb%, 20-99%), carboxyhemoglobin (COHb, 0.1-5.4%) and methemoglobin (MetHb, 0.2-4.6%)], were measured over 5-time points. The Royal College of Pathologists of Australasia’s (RCPA’s) criteria determined analyte instability. Survival analyses identified storage times at which 5% of the samples for various analytes became unstable.

RESULTS: COHb and MetHb were stable up to 3 h in slushed ice and at room temperature; pCO₂, pH was stable at room temperature for about 60 min and 3 h in slushed ice. Slushed ice shortened the storage time before pO₂ became unstable (from 40 to 20 min), and the instability increased when baseline pO₂ was ≥60 mmHg. The storage time for pO₂, pCO₂, pH, and CO-oximetry, when measured together, were limited by the pO₂.

CONCLUSIONS: When assessing pO₂ in plastic syringes, samples kept in slushed ice harm their stability. For simplicity’s sake, the data support storage times for blood gas and CO-oximetry panels of up to 40 min at room temperature if following RCPA guidelines.

PMID:37015069 | DOI:10.1515/cclm-2022-1085

J Laparoendosc Adv Surg Tech A. 2023 Apr 4. doi: 10.1089/lap.2022.0528. Online ahead of print.

ABSTRACT

Purpose: Dissecting and ligating the splenic artery is crucial for bleeding control during laparoscopic splenectomy (LS). However, for patients with portal hypertension from liver cirrhosis, it is difficult for identification and ligation because the splenic vessel is circuitous and dilated. The aim of this study was to describe a simple technique of constructing a tunnel behind the tail of the pancreas for occluding the splenic vessels during LS in patients with portal hypertension. Materials and Methods: The clinical data of 61 patients who underwent LS from April 2016 to January 2017 were retrospectively analyzed. In 27 patients, the tunnel construction (TC) behind the tail of the pancreas approach was performed owning to difficulty in dissecting and ligating the splenic artery (TC group), including 17 patients who received the TC method directly and 10 patients who received the TC method after trying to dissect the splenic artery. The remaining 34 patients underwent traditional ligating of the splenic artery (LA group). The peri- and postoperative outcomes of operative time, blood loss, conversion rate, postoperative oral diet intake, postoperative hospital stay, and postoperative complication rate of the two groups were analyzed. All the operations were completed by the same group of surgeons. Results: All 61 operations were successfully completed. Compared with patients in the LA group, patients in the TC group had less blood loss (120.37 ± 40.74 mL versus 162.65 ± 87.47 mL; t = -2.317, P = .024). There was no statistical difference of operative time, conversion rate, complication rate, postoperative hospital stays, and follow-up between the two groups. Conclusions: The technique of constructing a tunnel behind the tail of the pancreas for occluding the splenic vessels was effective and safe in those patients whose splenic artery was difficult to dissect and ligate.

PMID:37015064 | DOI:10.1089/lap.2022.0528

Dermatitis. 2023 Apr 4. doi: 10.1089/derm.2022.0040. Online ahead of print.

ABSTRACT

Background: Real-life data on severity and treatments in children with atopic dermatitis (AD) are needed to evaluate self-management. Objectives: To determine severity and use of topical treatments in children with AD in the general population. Furthermore, we aim to determine agreement and correlation between objective and subjective AD severity measures. Methods: Data were used from the Rotterdam Eczema Study, an observational prospective cohort study with an embedded pragmatic open-label randomized controlled trial. Descriptive statistics were used for baseline characteristics, medication use, and severity. Strength of agreement and correlation were determined using kappa analysis and Pearson correlation. Results: In total, 367 children (mean age 5.7 years) were recruited. The mean eczema area and severity index (EASI) score was 2.1 (±3.2) and mean patient-oriented eczema measure (POEM) score was 10.3 (±6.1). The majority applied emollients on a daily basis (54.9%) and had not used topical corticosteroids (TCSs) over the past week (51%). Based on severity banding of POEM and EASI, 49.9% and 24.9% of the children were undertreated, respectively. No evidence was found for an agreement between EASI and POEM (kappa 0.028, n = 178, P = 0.451). A moderate correlation between POEM, EASI, infants’ dermatitis quality of life index, and children’s dermatology life quality index was found. POEM showed higher correlation with quality of life (QoL) than EASI. Conclusion: Emollients were used sufficiently in the study population. Based on signs or symptoms, 24.9% and 49.9% of children are undertreated, respectively. POEM scores correlated better with QoL than with EASI scores. We argue that EASI underestimates severity of AD, and treatment based on EASI scores may lead to undertreatment of AD. Treating physicians should be aware of suboptimal use of TCSs.

PMID:37015063 | DOI:10.1089/derm.2022.0040

Anesthesiology. 2023 Apr 4. doi: 10.1097/ALN.0000000000004567. Online ahead of print.

ABSTRACT

BACKGROUND: Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheless, their comparative effects and side effects, timing, and respective variabilities, remain poorly understood. We tested the hypothesis that intravenous morphine and hydromorphone differ in onset, magnitude, duration and variability of analgesic and ventilatory effects.

METHODS: We conducted a randomized crossover study in healthy volunteers. Forty-two subjects received a 2-hour intravenous infusion of hydromorphone (0.05 mg/kg) or morphine (0.2 mg/kg) 1-2 weeks apart. We measured arterial opioid concentrations, analgesia in response to heat pain (maximally tolerated temperature, and verbal analog pain scores at discreet preset temperatures to determine half-maximum temperature effect), dark-adapted pupil diameter and miosis, end-expired CO2, and respiratory rate for 12 h after dosing.

RESULTS: For morphine and hydromorphone, respectively: maximum miosis was less (3.9 [3.4,4.2] vs 4.6 mm [4.0,5.0], P<0.001; median and 25%-75% quantiles) and occurred later (3.1 ± 0.9 vs 2.3 ± 0.7 h after infusion start, P<0.001; mean ± SD); maximum tolerated temperature was less (49 ± 2 vs 50 ± 2°C, P<0.001); verbal pain scores at end-infusion at the most informative stimulus (48.2°C) were 82 ± 4 and 59 ± 3 (P<0.001); maximum end-expired CO2 was 47 [45,50] and 48 mmHg [46,51] (P=0.007), and occurred later (5.5 ± 2.8 vs 3.0 ± 1.5 h after infusion start, P<0.001); respiratory nadir was 9 ± 1 and 11 ± 2 breaths/min (P<0.001) and occurred at similar times. Area under the temperature tolerance-time curve was less for morphine (1.8 [0.0,4.4]) than hydromorphone (5.4°C-h [1.6,12.1] P<0.001). Inter-individual variability in clinical effects did not differ between opioids.

CONCLUSIONS: For morphine compared to hydromorphone, analgesia and analgesia relative to respiratory depression were less, onset of miosis and respiratory depression was later, and duration of respiratory depression was longer. For each opioid, timing of the various clinical effects was not coincident. Results may enable more rational opioid selection, and suggest hydromorphone may have a better clinical profile.

PMID:37014986 | DOI:10.1097/ALN.0000000000004567

Anesth Analg. 2023 Apr 3. doi: 10.1213/ANE.0000000000006422. Online ahead of print.

ABSTRACT

BACKGROUND: Preoperative abnormal cognitive status is a risk factor for postoperative complications yet remains underdiagnosed. During propofol general anesthesia, intraoperative electroencephalography (EEG) variables, such as alpha band power (α-BP), correlate with cognitive status. This relationship under sevoflurane is unclear. We investigated whether EEG biomarkers of poor cognitive status found under propofol could be extended to sevoflurane.

METHODS: In this monocentric prospective observational study, 106 patients with intraoperative EEG monitoring were included (propofol/sevoflurane = 55/51). We administered the Montreal Cognitive Assessment (MoCA) scale to identify abnormal cognition (low MoCA) 1 day before intervention. EEG variables included delta to beta frequency band powers. Results were adjusted to age and drug dosage. We assessed depth of anesthesia (DoA) using the spectral edge frequency (SEF95) and maintained it within (8-13) Hz.

RESULTS: The difference in α-BP between low and normal MoCA patients was significantly larger among propofol patients (propofol: 4.3 ± 4.8 dB versus sevoflurane: 1.5 ± 3.4 dB, P = .022). SEF95 and age were not statistically different between sevoflurane and propofol groups. After adjusting to age and dose, low α-BP was significantly associated with low MoCA under propofol (odds ratio [OR] [confidence interval {CI}] = 0.39 [0.16-0.94], P = .034), but not under sevoflurane, where theta-band power was significantly associated with low MoCA (OR [CI] = 0.31 [0.13-0.73], P = .007).

CONCLUSIONS: We suggest that intraoperative EEG biomarkers of abnormal cognition differ between propofol and sevoflurane under general anesthesia.

PMID:37014984 | DOI:10.1213/ANE.0000000000006422

Anesthesiology. 2023 Apr 4. doi: 10.1097/ALN.0000000000004570. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. We hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy.

METHODS: We conducted a retrospective, international, multicenter study using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients < 18 years old were matched using age, ASA-PS status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April-May 2020) compared to pre-pandemic (April-May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis.

RESULTS: 3351 cases from 28 institutions were available with 1684 cases in the pre-pandemic cohort matched to 1618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 hours (IQR: 18, 67) in the pandemic cohort versus 28 hours (IQR: 18, 79) in the pre-pandemic cohort (adjusted coefficient, 1; 95% CI 0.39 to 1.61, P<0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period compared to the pre-pandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, pre-pandemic 313 (18.6%) versus pandemic 389 (24.1%), absolute difference of 5.5% (adjusted OR, 1.32; [95% CI 1.1 to 1.59]; P=0.003). Preoperative SARS CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 minutes (IQR: 430, 1112) with testing versus 414 minutes (IQR: 231, 770) without testing, adjusted coefficient, 306 minutes, (95% CI 241 to 371, P <0.001), and longer hospital length of stay, 31 hours (IQR: 20, 83) with testing versus 24 hours (IQR: 14, 68) without testing, adjusted coefficient, 7.0, (95% CI 2.7 to 11.3, P=0.002).

DISCUSSION: For children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.

PMID:37014980 | DOI:10.1097/ALN.0000000000004570

Arch Pathol Lab Med. 2023 Apr 5. doi: 10.5858/arpa.2022-0338-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: End-stage kidney disease (ESKD) is defined as renal impairment requiring renal replacement therapy to sustain life. With a 1-year mortality of ∼20% to 30%, many die of complications related to this disease.

OBJECTIVE.—: To determine the percentage of autopsy cases of decedents with ESKD in which the contribution of ESKD to death is accurately reflected in the final report.

DESIGN.—: Autopsy case records were retrospectively reviewed at 4 institutions (Yale New Haven Hospital, University of Chicago Medical Center, University of Illinois at Chicago Hospital, University of Iowa Hospital). Clinical, macroscopic, and microscopic autopsy findings were reviewed, with attention to renal disease findings.

RESULTS.—: One hundred sixty decedents with documented ESKD and premortem dialysis were identified who underwent autopsy assessment. ESKD was implicated as a cause of death (CoD) or significant contributing factor in 44 cases (28%), but not in the remaining 116 cases (72%). Cardiovascular disease was the most common CoD in ESKD. There was significant interpathologist variation in the inclusion of ESKD as a CoD across institutions. These rates ranged from 85% correlation (23 of 27 cases), to 13% (4 of 31 and 8 of 62 cases at 2 institutions), and 22.5% (9 of 40 cases) across the 4 participating institutions.

CONCLUSIONS.—: The recognition at autopsy of ESKD as a CoD or contributing CoD at autopsy in patients undergoing dialysis remains low (28%). The detrimental impact of ESKD is not reflected in hospital autopsy reports, which carries implications for collection of vital statistics and allocation of research funding for kidney diseases.

PMID:37014976 | DOI:10.5858/arpa.2022-0338-OA