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Familial parathyroid tumours-comparison of clinical profiles between syndromes

J Endocrinol Invest. 2023 Feb 13. doi: 10.1007/s40618-023-02032-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT).

OBJECTIVE: Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes.

METHODS: Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed.

RESULTS: Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1 mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2 mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8 mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01).

CONCLUSION: The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes.

PMID:36780067 | DOI:10.1007/s40618-023-02032-4

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CIN2 + detection in high-risk HPV patients with no or minor cervical cytologic abnormalities: a clinical approach validated by machine learning

Arch Gynecol Obstet. 2023 Feb 13. doi: 10.1007/s00404-023-06953-6. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the feasibility and diagnostic value of the combination of colposcopy, cytology and hrHPV (high-risk human papilloma virus) PCR (polymerase chain reaction) testing in patients with no or minor cytologic abnormalities and HPV high risk infection and to find the best predictors for the presence of CIN2 + in this patient collective.

METHODS: Three hundred and thirty-four hrHPV patients with normal cytology or minor cytologic abnormalities who had a colposcopic examination at the center of colposcopy at the university hospital Aachen in 2021 were enrolled in this retrospective cohort analysis. Multivariate logistic regression and a machine-learning technique (random forests, leave-one-out analysis) were used.

RESULTS: The overall risk for CIN2 + in hrHPV-positive patients with normal cytology was 7.7% (N = 18) (5% for CIN3 +), 18% (N = 16) (10.1% for CIN3 +) in patients with PAP IIp (ASC-US) and 62.5% (N = 5) (25% for CIN3 +) in patients with PAP IIg (AGC). Variables that show a statistically significant influence for the CIN-status are ‘major change’ as the result of colposcopy, transformation zone type T1, PAP IIg upon referral (AGC) and hrHPV category 1a (HPV 16/18) detection. Using machine learning (random forests) techniques, the main influencing variables were confirmed. A monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3 (in accordance to the IACR guidelines) was found.

CONCLUSION: In the collective of hrHPV patients with no or minor cytologic abnormalities, the result of colposcopy and HPV PCR status are key predictors for the detection of CIN2 + with a monotonously decreasing risk for CIN2 + from hrHPV category 1a to 3.

PMID:36780042 | DOI:10.1007/s00404-023-06953-6

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Variation of butyrate production in the gut microbiome in type 2 diabetes patients

Int Microbiol. 2023 Feb 13. doi: 10.1007/s10123-023-00324-6. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetes mellitus type 2 is a common disease that poses a challenge to the healthcare system. The disease is very often diagnosed late. A better understanding of the relationship between the gut microbiome and type 2 diabetes can support early detection and form an approach for therapies. Microbiome analysis offers a potential opportunity to find markers for this disease. Next-generation sequencing methods can be used to identify the bacteria present in the stool sample and to generate a microbiome profile through an analysis pipeline. Statistical analysis, e.g., using Student’s t-test, allows the identification of significant differences. The investigations are not only focused on single bacteria, but on the determination of a comprehensive profile. Also, the consideration of the functional microbiome is included in the analyses. The dataset is not from a clinical survey, but very extensive.

RESULTS: By examining 946 microbiome profiles of diabetes mellitus type 2 sufferers (272) and healthy control persons (674), a large number of significant genera (25) are revealed. It is possible to identify a large profile for type 2 diabetes disease. Furthermore, it is shown that the diversity of bacteria per taxonomic level in the group of persons with diabetes mellitus type 2 is significantly reduced compared to a healthy control group. In addition, six pathways are determined to be significant for type 2 diabetes describing the fermentation to butyrate. These parameters tend to have high potential for disease detection.

CONCLUSIONS: With this investigation of the gut microbiome of persons with diabetes type 2 disease, we present significant bacteria and pathways characteristic of this disease.

PMID:36780038 | DOI:10.1007/s10123-023-00324-6

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Distal shunt placement in pediatric ventriculoperitoneal shunt surgery: an international survey of practice

Childs Nerv Syst. 2023 Feb 13. doi: 10.1007/s00381-023-05855-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Ventriculoperitoneal shunt (VPS) surgery is a common treatment for hydrocephalus in children and adults, making it one of the most common procedures in neurosurgery. Children being treated with a VPS often require several revisions during their lifetime with a lifetime revision rate of up to 80%. Several different techniques exist for inserting the distal catheter, while mini-laparotomy, trocar, or laparoscopy is traditionally used. As opposed to adults, only few studies exist, comparing the outcome of the different distal catheter placement techniques in children. This international survey aims to investigate the current daily practice concerning distal shunt placement techniques in children.

MATERIAL AND METHODS: An online questionnaire investigating the different techniques used to place the distal catheter in pediatric VPS surgery was distributed internationally. All results were analyzed using descriptive and comparative statistics.

RESULTS: A total of 139 responses were obtained. Mini-laparotomy was reported to be the most frequently used technique (n = 104, 74.8%) for distal shunt placement in children, while laparoscopic or trocar-assisted placements were only used by 3.6% (n = 5) and 21.6% (n = 30) of all respondents, respectively. Over half (n = 75, 54.0%) of all respondents do not believe that laparoscopic placement improves the outcome.

CONCLUSION: This international survey shows that mini-laparotomy is the most frequently used technique for distal VPS placement in children all over the world. Further randomized trials are needed to elucidate this matter.

PMID:36780037 | DOI:10.1007/s00381-023-05855-x

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Psychosocial functioning mediates change in motor and cognitive function throughout neurorehabilitation for adults with acquired brain injury (ABI-RESTaRT)

Neurol Sci. 2023 Feb 13. doi: 10.1007/s10072-023-06645-8. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the mediational role of change in psychosocial abilities, adjustment and participation on change in motor and cognitive function from admission to discharge from a staged community-based brain injury rehabilitation (SCBIR) service in Western Australia, 2011-2020.

METHODS: A retrospective cohort study of n = 324 adults with ABI enrolled in SCBIR using routinely collected rehabilitation outcome measures data. Motor and cognitive function were assessed with the UK Functional Independence and Assessment Measure and psychosocial function with the Mayo-Portland Adaptability Inventory-4. Six multilevel mediation regression analyses were conducted to determine whether change in psychosocial function (abilities, adjustment and participation) mediated change in motor and cognitive function from admission to discharge.

RESULTS: Participants demonstrated clinically significant improvements in both motor (+ 11.8, p < 0.001) and cognitive (+ 9.5, p < 0.001) functioning from admission to discharge. Statistically significant improvements in psychosocial abilities (- 4.8, p < 0.001), adjustment (- 2.9, p = 0.001) and participation (- 2.5, p < 0.001) were also seen but were not clinically significant. Mediation analyses showed that participation accounted for 81% of improvements in motor function at discharge and 71% of cognitive function improvements. Adjustment accounted for 26% and 32% of change in motor and cognitive function, respectively. Abilities accounted for 60% of change in cognitive function but did not significantly influence change in motor function. Changes in psychosocial participation fully mediated change in motor function during neurorehabilitation.

CONCLUSIONS: Psychosocial function, particularly participation, is an important driver of motor and cognitive recovery throughout neurorehabilitation. Functional rehabilitation programs should target psychosocial improvement as an important mechanism of change.

PMID:36780031 | DOI:10.1007/s10072-023-06645-8

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The outcomes of cataract surgery in eyes with Fuchs uveitis

J Ophthalmic Inflamm Infect. 2023 Feb 13;13(1):4. doi: 10.1186/s12348-022-00320-3.

ABSTRACT

BACKGROUND: To evaluate clinical results in eyes undergoing phacoemulsification intraocular lens (IOL) implantation due to Fuchs, uveitis (FU) related complicated cataract.

METHODS: Post-surgical outcomes of 56 eyes of 55 FU patients were evaluated retrospectively. Three groups were formed according to the IOL model: hydrophilic SAF6125 (Optima fold) acrylic, hydrophobic SN60AT (Alcon), and hydrophobic AAB00 (Abbott). Postoperative posterior capsular opacification (PCO) development and PCO development time, neodymium number: YAG laser posterior capsulotomy rate, giant cell (GC) deposition on the IOL, and the development time of GC deposits were compared among the groups. All patients were followed postoperatively on the 1st day, 1st week, 2nd and 6th weeks, and then at 3-month intervals.

RESULTS: The hydrophilic SAF6125 IOL was implanted in 10 eyes, hydrophobic SN60AT in 24 eyes and AAB00 IOL in 22 eyes. The mean postoperative follow-up time was 34.1 ± 30.1 (6-144) months. PCO developed in 7 eyes (70%) in the hydrophilic SAF6125 group, 17 eyes (70.8%) in the hydrophobic SN60AT and 13 eyes (59.1%) in the AAB00 group. There was no statistically significant difference among the three IOL groups in the PCO development, the PCO development time and YAG laser capsulotomy rates (P = 0.674, P = 0.111, and P = 0.507, respectively). The PCO development time was significantly longer in the hydrophobic SN60AT than AAB00 group (P = 0.027). GC deposits were detected in 3 eyes (30%) in the hydrophilic SAF6125 group, 7 eyes (29.1%) in the hydrophobic SN60AT and 3 eyes (13.6%) in the AAB00 group. GC deposition and the development time of GC deposits were similar among the three IOL groups (P = 0.575, P = 0.804). At the final follow-up, BCVA was ≥ 20/40 in 41 eyes (73.2%).

CONCLUSION: The GC deposits and PCO development were the most important problems in these eyes with hydrophilic or hydrophobic IOLs despite good visual and postoperative results. New developments are needed in terms of IOL design or content in eyes with FU.

PMID:36780022 | DOI:10.1186/s12348-022-00320-3

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Challenges in antibody structure prediction

MAbs. 2023 Jan-Dec;15(1):2175319. doi: 10.1080/19420862.2023.2175319.

ABSTRACT

Advances in structural biology and the exponential increase in the amount of high-quality experimental structural data available in the Protein Data Bank has motivated numerous studies to tackle the grand challenge of predicting protein structures. In 2020 AlphaFold2 revolutionized the field using a combination of artificial intelligence and the evolutionary information contained in multiple sequence alignments. Antibodies are one of the most important classes of biotherapeutic proteins. Accurate structure models are a prerequisite to advance biophysical property predictions and consequently antibody design. Specialized tools used to predict antibody structures based on different principles have profited from current advances in protein structure prediction based on artificial intelligence. Here, we emphasize the importance of reliable protein structure models and highlight the enormous advances in the field, but we also aim to increase awareness that protein structure models, and in particular antibody models, may suffer from structural inaccuracies, namely incorrect cis-amide bonds, wrong stereochemistry or clashes. We show that these inaccuracies affect biophysical property predictions such as surface hydrophobicity. Thus, we stress the importance of carefully reviewing protein structure models before investing further computing power and setting up experiments. To facilitate the assessment of model quality, we provide a tool “TopModel” to validate structure models.

PMID:36775843 | DOI:10.1080/19420862.2023.2175319

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Postoperative Segmental Motion up to 1 Year Following Single-Level Anterior Cervical Discectomy and Fusion: Plate versus Non-plate

Asian Spine J. 2023 Feb 13. doi: 10.31616/asj.2022.0192. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective observational study.

PURPOSE: This study aimed to investigate the impact of plating on postoperative serial segmental motion and its correlation with clinical outcomes in single-level anterior cervical discectomy and fusion (ACDF) for up to 1 year.

OVERVIEW OF LITERATURE: The advantages and disadvantages of using cervical plating in ACDF have been well discussed; however, few studies compared the early serial segmental motions at the postoperative level between plating and non-plating.

METHODS: In retrospectively collected data, 149 patients who underwent single-level ACDF for degenerative disease were enrolled and divided into non-plating (n=66) and plating (n=83). Interspinous motion (ISM) at the arthrodesis segment, Numeric Rating Scale (NRS) for neck pain, and Neck Disability Index (NDI) were serially evaluated at 3, 6, and 12 months postoperatively. Predictable factors for fusion, including age, sex, plating, diabetes, smoking, and type of grafts, were investigated, and fusion was defined as ISM <1 mm.

RESULTS: In both groups, ISM was the highest at 3 months and gradually decreased thereafter, and the plating group showed significantly lower serial ISM than the non-plating group at 12 months. The plating group had lower NRS and NDI scores than the nonplating group at 12 months, and the difference in the NRS scores was statistically significant, particularly at 3 and 6 months, although that of the NDI scores was not. In a multivariate analysis, plating was the most powerful predictor for fusion.

CONCLUSIONS: Plating significantly decreases the serial ISM compared with non-plating in single-level ACDF, and such decreased motion is correlated with decreased neck pain until 12 months postoperatively, particularly at 3 and 6 months. Given that plating was the most predictive factor for fusion, we recommend plating even in single-level ACDF for better early clinical outcomes.

PMID:36775832 | DOI:10.31616/asj.2022.0192

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Collective review of pancreatic carcinosarcoma, a very rare pancreatic malignancy

Ann Hepatobiliary Pancreat Surg. 2023 Feb 13. doi: 10.14701/ahbps.22-078. Online ahead of print.

ABSTRACT

Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of “Pancreatic” or “Pancreas” and “carcinosarcoma” or “carcinosarcomatous”. The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

PMID:36775825 | DOI:10.14701/ahbps.22-078

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Cognitive behavioral therapy achieves better benefits in relieving postoperative pain and improving joint function: A systematic review and meta-analysis of randomized controlled trials

J Orthop Sci. 2023 Feb 10:S0949-2658(23)00013-1. doi: 10.1016/j.jos.2023.01.007. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive behavioral therapy (CBT) is a structured, short-term psychotherapy approach that may have positive effects in terms of relieving postoperative pain. The main objective of this study was to determine the effect of CBT on pain and joint function in patients after total joint arthroplasty.

METHODS: We searched 3 electronic databases including randomized controlled studies (RCTs) using CBT as an intervention. The main results of this study were to determine pain intensity by NRS, VAS, WOMAC pain Scale, PCS, and joint function by HHS, OKS, EQ-5D, ROM. Data extraction and quality assessment of included RCTs were independently performed by the authors and date analysis was performed by RevMan V.5.4.

RESULTS: Among the 605 studies, 9 RCTS were included in this systematic review and meta-analysis. The study showed that the difference between CBT and usual care groups in PCS (≤3months), NRS, VAS (≤3months) were statistically significant (P < 0.05); the difference between CBT and usual care groups in PCS (≥12months), WOMAC Pain Scale, and VAS (≥12months) were not statistically significant (P > 0.05), indicating that CBT can improve pain in patients after arthroplasty in the early term. In addition, the difference between CBT and usual care groups in OKS (≤3months), HSS, ROM (≤3months), EQ-5D (≤3months) were not statistically significant (P > 0.05); the difference between CBT and usual care groups in EQ-5D (≥12months) were statistically significant (P < 0.05), indicating that the quality of life in patients after total joint arthroplasty were improved with the extension of follow-up time.

CONCLUSIONS: This study shows that CBT can relieve pain in patients with total joint arthroplasty in the early postoperative period and improve quality of life to some extent over time.

PMID:36775785 | DOI:10.1016/j.jos.2023.01.007