Prediction of the Uric Acid Component in Nephrolithiasis Using Simple Clinical Information about Metabolic Disorder and Obesity: A Machine Learning-Based Model

There is a great need for a diagnostic tool using simple clinical information collected from patients to diagnose uric acid (UA) stones in nephrolithiasis. We built a predictive model making use of machine learning (ML) methodologies entering simple parameters easily obtained at the initial clinical visit. Socio-demographic, health, and clinical data from two cohorts (A and B), both diagnosed with nephrolithiasis, one between 2012 and 2016 and the other between June and December 2020, were collected before nephrolithiasis treatment. A ML-based model for predicting UA stones in nephrolithiasis was developed using eight simple parameters—sex, age, gout, diabetes mellitus, body mass index, estimated glomerular filtration rate, bacteriuria, and urine pH. Data from Cohort A were used for model training and validation (ratio 3:2), while data from Cohort B were used only for validation. One hundred and forty-six (13.3%) out of 1098 patients in Cohort A and 3 (4.23%) out of 71 patients in Cohort B had pure UA stones. For Cohort A, our model achieved a validation AUC (area under ROC curve) of 0.842, with 0.8475 sensitivity and 0.748 specificity. For Cohort B, our model achieved 0.936 AUC, with 1.0 sensitivity, and 0.912 specificity. This ML-based model provides a convenient and reliable method for diagnosing urolithiasis. Using only eight readily available clinical parameters, including information about metabolic disorder and obesity, it distinguished pure uric acid stones from other stones before treatment.     

Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response

Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. Here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of HIV-1 and avian sarcoma virus retroviral vector DNA that is joined to host DNA in the population of infected cells and also in the number of transduced cells. These changes were observed at caffeine concentrations that had little or no effect on overall cell growth, synthesis, and nuclear import of the viral DNA, or the activities of the viral integrase in vitro. Substantial reductions in the amount of host-viral-joined DNA in the infected population, and in the number of transductants, were also observed in the presence of a dominant-negative form of the ATR protein, ATRkd. After infection, a significant fraction of these cells undergoes cell death. In contrast, retroviral transduction is not impeded in ATM-deficient cells, and addition of caffeine leads to the same reduction that was observed in ATM-proficient cells. These results suggest that activity of the ATR kinase, but not the ATM kinase, is required for successful completion of the viral DNA integration process and/or survival of transduced cells. Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development.     

Celiac artery stenting: a new strategy for patients with pancreaticoduodenal artery aneurysm associated with stenosis of the celiac artery

We report a new strategy—celiac artery stenting—to relieve stenosis of the celiac arterial root. This was performed in two patients with pancreaticoduodenal artery (PDA) aneurysm associated with a stenotic celiac arterial root. The first patient was a 66-year-old man complaining of abrupt onset of upper abdominal pain. Abdominal computed tomography revealed a huge retroperitoneal hematoma behind the duodenum, and superior mesenteric artery (SMA) angiography demonstrated an aneurysm arising from inferior pancreaticoduodenal artery and celiac arteriography showed a stenotic celiac arterial root. Transcatheter embolization of the aneurysm was tried, but failed. Because of his unstable hemodynamics, emergent laparotomy with resection of the aneurysm was performed. Fourteen days after the operation, percutaneous transluminal angioplasty with celiac arterial stenting was done. The patient was discharged 2 days later, and has had no further bleeding episode for 3 years. The second patient was a 46-year-old woman, who also complained of acute upper abdominal pain. Abdominal computed tomography disclosed a huge retroperitoneal hematoma, and selective SMA angiography demonstrated an aneurysm arising from the inferior pancreaticoduodenal artery, and celiac arteriography showed a stenotic celiac arterial root. Because angiography showed no active bleeding from the aneurysm, percutaneous transluminal angioplastic stenting of the stenotic celiac artery was performed. She was discharged 5 days later and has had no further bleeding episode for 2 years. Celiac arterial stenting, as shown in our two patients, could be easily and safely employed in patients with PDA aneurysm associated with a stenotic celiac arterial root to release the stenosis of the celiac arterial root and to prevent further possible bleeding.     

Thoracic aortic aneurysm with aortobronchial fistula: a thirteen-year experience

PURPOSE: This study investigated the causes of aortobronchial fistula, clinical features, diagnostic modalities, and prognostic factors. PARTICIPANTS: A retrospective analysis of 17 patients with aortobronchial fistula secondary to thoracic aortic aneurysm was studied. METHODS: Retrospective chart review was used. RESULTS: Atherosclerosis (47.1%), infection (23.5%), and previous thoracic vascular surgery (17.6%) accounted for most causes. Most patients (94.1%) experienced at least 1 episode of hemoptysis. Chest computer tomography is the most useful tool and revealed hematoma or consolidation around the aneurysm in more than half of our patients. Bronchoscopy and aortoangiogram frequently did not demonstrate an aortobronchial fistula. The 6 patients in the surgery group all survived, in contrast to 100% mortality in the non-surgery group. The average interval between initial presentation of hemoptysis and surgical intervention in the surgery group is 68 days, in contrast to 170 days between initial presentation of hemoptysis and death in the non-surgery group. CONCLUSIONS: A high index of suspicion will decrease delayed diagnosis. Early diagnosis and emergent surgery are 2 prognostic factors for survival.     

Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis

BACKGROUND: Thyrotoxic periodic paralysis (TPP), familial periodic paralysis (FPP), and sporadic periodic paralysis (SPP) are common causes of hypokalemic periodic paralysis and have similar clinical presentations, thus possibly sharing the identical mutations. METHODS: We analyzed the role of the three known CACNA1S gene mutations (R528H, R1239H, and R1239G) in Chinese patients, including two FPP families, 36 TPP patients, 12 SPP patients, and their relatives. Fifty unrelated healthy subjects were also studied. Genomic DNA was prepared from the peripheral blood of all patients, their family members, and healthy subjects. Mutations of the CACNA1S gene were screened using polymerase chain reaction-based restriction analysis. RESULTS: Two FPP families had the R528H point mutation, but with incomplete penetrance occurring more commonly in men than in women. Only one SPP patient had a de novo mutation (R528H). None of the TPP patients had mutations in the three hot spots. CONCLUSION: Patients with FPP have R528H mutations in the CACNA1S gene. Only a few patients with SPP may share similar mutations with FPP. TPP patients do not carry any of the three known gene mutations.     

Genetics of Somatic Mammalian Cells: Lethal Antigens as Genetic Markers for Study of Human Linkage Groups

The antigen that causes killing of at least 98% of a human cell population treated with a 1% solution of a specific rabbit antiserum in the presence of complement is a sensitive genetic marker. The rapid loss of human chromosomes in human-Chinese hamster cell hybrids makes possible a convenient test of linkage relationships with this marker. Hybrid clones with and without the lethal antigen were isolated and analyzed. In 76 clones and subclones studied, 41 carried both the lethal antigen and the lactic dehydrogenase-A marker, 35 carried neither, and no clones contained only one of the two markers. In contrast to this clear demonstration of linkage, absence of linkage was found between the lethal antigen and the following markers: Lactic dehydrogenase B, NAD-dependent malic dehydrogenase, NADP-dependent malic dehydrogenase, glucose-6-phosphate dehydrogenase, phosphoglucomutase, glutamate oxaloacetate transaminase, indophenol oxidase, glucose phosphate isomerase, proline, inositol, hypoxanthine B, and glycine A. This lethal antigen appears to be carried on a single human autosome.     

A Placebo-Controlled Trial of Dextromethorphan as an Adjunct in Opioid-Dependent Patients Undergoing Methadone Maintenance Treatment

Background:

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

Methods:

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor–β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

Results:

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

Conclusions:

We provide evidence—decreased concomitant heroin use—of low-dose add-on DM’s efficacy for treating opioid-dependent patients undergoing MMT.     

Alterations of bone markers in obese patients with type 2 diabetes after bariatric surgery: A meta-analysis and systemic review of randomized controlled trials and cohorts

Background:The aim of this study is to evaluate the alterations in bone mineral density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control.Methods:We searched 4 electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide level, and parathyroid hormone level.Results:Three randomized clinical trials and 2 observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: −2.90, 95% CI: −2.99∼−2.81, P < .00001) and total hip BMD loss (mean difference: −5.81, 95% CI: −9.22∼−2.40, P = .0008). As to biochemical markers of bone metabolism, we found significantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57–13.75, P < .00001). However, higher C-terminal telopeptide level and parathyroid hormone level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11–0.48, P = .002; mean difference: 1.56, 95% CI: 0.84–2.27, P < .0001).Conclusions:RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of perioperative and postsurgical supplementation should be evaluated.