BACKGROUND: Inborn errors of immunity (IEIs) are rare genetic disorders primarily identified in children due to their significant effects on immune system functionality. However, an increasing number of IEI cases are being diagnosed in adults, attributed to delayed presentation or advancements in diagnostic capabilities. This study explores the clinical and immunologic distinctions between IEIs diagnosed in adulthood versus childhood, shedding light on their differential presentations, the impact of diagnostic delays, and treatment outcomes.
METHODS: This study focused on 122 adult patients with IEI above 17 years old, diagnosed in adulthood or childhood. We collected comprehensive data on demographics, clinical presentations, genetic mutations, and therapeutic interventions.
RESULTS: The study revealed that 72.9% of participants were diagnosed in adulthood, facing a median diagnostic delay of 96 months. Diagnostic delays were longer in adults (132 months vs. 24 months) than in children. The most common clinical manifestations at onset were recurrent infections (46.7%) and autoimmunity (18%). Predominantly antibody deficiency was the most frequently diagnosed immunodeficiency (54.9%), followed by immunodysregulation at a rate of 26.2%. A higher incidence of immune thrombocytopenia or other complications, such as hepatomegaly and enteropathy, was observed in adult-diagnosed patients with IEI. Malignancies were more prevalent in patients with adult-onset IEI compared to those with childhood-onset (18.1% vs. 5.2%). Overall, 15 different malignancies were recorded in 13 patients (10.6%), including lymphomas and cancers of the stomach, thymus, skin, breast, and colon.
CONCLUSIONS: The findings highlight a considerable diagnostic delay in recognizing IEI, especially in adults, and illustrate distinct differences in disease manifestation and progression between adult-onset and delayed-diagnosis groups.

OBJECTIVE: Thiopurine therapy is a cornerstone in the treatment of inflammatory bowel disease (IBD). We aimed to assess the effect of thiopurines on cancer risk in IBD according to drug exposure and age.
METHODS: Danish national registers were used to identify incident IBD patients, exposure to drugs and status of cancers, in 1996-2018. Cox regressions were used to compare cancer risks in IBD and non-IBD individuals and to assess IBD patients\' cumulative drug exposure and the association to first cancer, excluding non-melanoma skin cancer.
RESULTS: We followed 43,419 IBD patients for a median of 8.2 years (IQR:3.7-14.2) after IBD diagnosis. Cancer was reported in 3,128 (7.2%) IBD patients. The risk of cancer was increased in IBD patients in all age categories compared to non-IBD individuals (<50 years (aHR: 1.59 (95%CI: 1.43-1.77)), 50-65 years (aHR: 1.31 (95%CI: (1.19-1.44)), and >65 years (aHR: 1.14 (95%CI: 1.05-1.24)). Monotherapy and combination therapy were associated with cancer (aHR:1.36 (95%CI:1.17-1.57) and (aHR:2.49 (95%CI:1.64-3.78), respectively) compared to unexposed IBD patients. Among elderly (>65 years), the aHR was 2.79 (95%CI:1.24-6.28) in those receiving combination therapy. In patients discontinuing thiopurines, aHRs returned to the level of unexposed (aHR:0.89 (95%CI:0.78-1.01)). The aHR was positively associated with cumulative thiopurine exposure and in patients with >5 years of exposure, reaching aHR 1.36 (95%CI:1.15-1.61).
CONCLUSIONS: Thiopurines were associated with increased hazard of cancer, especially when used in combination therapy in the elderly. The hazard increased by 36% when patients were exposed to thiopurines for more than five years. Reassuringly, the hazard returned to baseline after discontinuation of thiopurines.

This study aimed to explore whether the prediagnostic use of metformin and statins is associated with the prognosis of patients with hepatocellular carcinoma (HCC) and type 2 diabetes. We identified 1383 eligible individuals who had both type 2 diabetes and HCC diagnosed between 1998 and 2017 from several Finnish registers. Cox models were fitted for cause-specific and all-cause mortality in relation to the use of antidiabetic medications and statins prior to the HCC diagnosis. Prediagnostic metformin use was associated with decreased overall mortality (hazard ratio 0.84, 95% confidence interval 0.74-0.94) compared with nonuse in patients with type 2 diabetes. Similarly, slightly decreased HCC mortality and other-cause mortality were observed among metformin users. The results were inconclusive regarding metformin use and both overall and HCC mortality among patients with localized HCC. No discernible contrast between statin users and nonusers was found in overall mortality nor HCC mortality in either the whole cohort or patients with localized cancer.

暂无摘要。

BACKGROUND: Gastrointestinal angiodysplasia (GIAD) is a rare diagnosis among the general population. We aimed to identify risk factors for GIADs and to determine the frequency rate in the general population.
METHODS: A population-based retrospective study was performed including patients diagnosed with upper (stomach/duodenum) or lower (small bowel/colon) GIADs based on diagnostic codes from a large health maintenance organization. Control groups were matched for age and gender. Additional data including demographics, comorbidities, malignancies, and medications were collected.
RESULTS: 991 upper GIADs and 3336 lower GIADs were included, compared to 7217 and 32,802 controls. The overall prevalence of GIAD was 0.092 %. 88 % of the upper and 85 % of the lower GIADs were diagnosed at ages ≥60, peaking at a prevalence of 0.37 % for ages 71-80. The most significant risk factors for GIADs included liver cirrhosis (OR 4.0 for lower GIAD and OR 7.0 for upper GIAD, p < 0.001), hypertension (OR 2.3 for lower GIAD and OR 2.8 for upper GIAD, p < 0.001) and aortic stenosis (OR 2.8 for lower GIAD and OR 2.0 for upper GIAD, p < 0.001). Other significant risk factors included ischemic heart disease, chronic renal failure, female gender, and chronic obstructive pulmonary disease. Interestingly, both upper and lower GIADs were found to be significantly less frequent in patients with malignancy.
CONCLUSIONS: Identification of the clinical conditions and demographic factors associated with GIAD may improve our understanding of the etiology and the optimal treatment modalities for this rare condition.

BACKGROUND: The Laparoscopic Approach to Cervical Cancer study results revolutionized our understanding of the best surgical management for this disease. After its publication, the guidelines state that the standard and recommended approach for radical hysterectomy is an open abdominal approach. Nevertheless, the effect of the Laparoscopic Approach to Cervical Cancer trial on real-world changes in the surgical approach to radical hysterectomy remains elusive.
OBJECTIVE: This study aimed to investigate the trends and routes of radical hysterectomy and to evaluate postoperative complication rates before and after the Laparoscopic Approach to Cervical Cancer trial (2018).
METHODS: The National Surgical Quality Improvement Program registry was used to examine radical hysterectomy for cervical cancer performed between 2012 and 2022. This study excluded vaginal radical hysterectomies and simple hysterectomies. The primary outcome measures were the trends in the route of surgery (minimally invasive surgery vs laparotomy) and surgical complication rates, stratified by periods before and after the publication of the Laparoscopic Approach to Cervical Cancer trial in 2018 (2012-2017 vs 2019-2022). The secondary outcome measure was major complications associated specifically with the different routes of surgery.
RESULTS: Of the 3611 patients included, 2080 (57.6%) underwent laparotomy, and 1531 (42.4%) underwent minimally invasive radical hysterectomy. There was a significant increase in the minimally invasive surgery approach from 2012 to 2017 (45.6% in minimally invasive surgery in 2012 to 75.3% in minimally invasive surgery in 2017; P<.01) and a significant decrease in minimally invasive surgery from 2018 to 2022 (50.4% in minimally invasive surgery in 2018 to 11.4% in minimally invasive surgery in 2022; P<.001). The rate of minor complications was lower in the period before the Laparoscopic Approach to Cervical Cancer trial than after the trial (317 [16.9%] vs 288 [21.3%], respectively; P=.002). The major complication rates were similar before and after the Laparoscopic Approach to Cervical Cancer trial (139 [7.4%] vs 78 [5.8%], respectively; P=.26). The rates of blood transfusions and superficial surgical site infections were lower in the period before the Laparoscopic Approach to Cervical Cancer trial than in the period after the trial (137 [7.3%] vs 133 [9.8%] [P=.012] and 20 [1.1%] vs 53 [3.9%] [P<.001], respectively). In a comparison of minimally invasive surgery vs laparotomy radical hysterectomy during the entire study period, patients in the minimally invasive surgery group had lower rates of minor complications than in those in the laparotomy group (190 [12.4%] vs 472 [22.7%], respectively; P<.001), and the rates of major complications were similar in both groups (100 [6.5%] in the minimally invasive surgery group vs 139 [6.7%] in the laparotomy group; P=.89). In a specific complications analysis, the rates of blood transfusion and superficial surgical site infections were lower in the minimally invasive surgery group than in the laparotomy group (2.4% vs 12.7% and 0.6% vs 3.4%, respectively; P<.001; for both comparisons), and the rate of deep incisional surgical site infections was lower in the minimally invasive surgery group than in the laparotomy group (0.2% vs 0.7%, respectively; P=.048). In the multiple logistic regression analysis, the route of radical hysterectomy was not independently associated with the occurrence of major complications (adjusted odds ratio, 1.02; 95% confidence interval, 0.63-1.65).
CONCLUSIONS: Although the proportion of minimally invasive radical hysterectomies decreased abruptly after the Laparoscopic Approach to Cervical Cancer trial, there was no change in the rate of major postoperative complications. In addition, the hysterectomy route was not associated with major postoperative complications.

BACKGROUND: The evolution of disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) has improved patient prognosis. However, more real-world safety/effectiveness data comparing methotrexate (MTX), tofacitinib, tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic DMARDs (bDMARDs) are warranted.
METHODS: The CorEvitas RA Japan registry was used to identify patients with rheumatologist-diagnosed RA who initiated MTX/tofacitinib/TNFi/non-TNFi bDMARDs. Safety outcomes included incidence of major adverse cardiovascular events (MACE), total cardiovascular disease, total serious infections, total herpes zoster, and total malignancies (excluding non-melanoma skin cancer). Effectiveness outcomes included change from baseline (Δ) in Clinical Disease Activity Index (CDAI) and proportion of patients achieving a minimum clinically important difference (MCID) in CDAI at month 6. Adjusted regression models were fit; marginal means were estimated.
RESULTS: Overall, 1972 patients were included in the safety cohort: MTX (N = 298); tofacitinib (N = 253); TNFi (N = 663); non-TNFi (N = 758). Mean follow-up time was 3.8, 2.9, 3.0, and 2.9 years for MTX, tofacitinib, TNFi, and non-TNFi, respectively. Adjusted incidence rates (IRs, patients with events/100 patient-years [95% confidence intervals]) for MACE and total cardiovascular disease, respectively, were numerically lower for MTX (0.34 [0, 0.83]; 0.42 [0, 0.92]) and TNFi (0.09 [0, 0.27]; 0.61 [0.15, 1.07]) versus tofacitinib (0.48 [0, 1.20]; 2.30 [0.38, 4.22]) and non-TNFi (0.77 [0.35, 1.19]; 1.28 [0.73, 1.82]). Serious infections were numerically higher for non-TNFi (4.47 [3.38, 5.56]); herpes zoster was higher for tofacitinib (7.41 [4.52, 10.29]), versus other groups. IRs for malignancies were comparable between groups. Mean ΔCDAI and rates of achieving MCID in CDAI at month 6 were generally greater with tofacitinib versus other groups.
CONCLUSIONS: Some variations in incidence of safety outcomes were observed between treatments, while certain effectiveness outcomes favored tofacitinib. Sample size variation between groups and low number of safety events limited the analysis. Further studies are warranted to investigate observed differences.
RESULTS: GOV: NCT05572567.

Breast cancer (BC) and depression are globally prevalent problems. Numerous reviews have indicated the high prevalence of depression among BC survivors. However, the long-term impact of depression on survival among BC survivors has not been well explored. For this investigation, we aimed to explore the relationship between BC, depression, and mortality from a national random sample of adult American women. Data from the U.S. National Health and Nutrition Examination Survey (years 2005-2010) were linked with mortality data from the National Death Index up to December 31st, 2019. A total of 4719 adult women (ages 45 years and older) were included in the study sample with 5.1% having breast cancer and more than a tenth (12.7%) having depression. The adjusted hazard ratio (HR) for all-cause mortality risk among those with BC was 1.50 (95% CI = 1.05-2.13) compared to those without BC. In the adjusted analysis, the risk of all-cause mortality was highest among women with both depression and BC (HR = 3.04; 95% CI = 1.15-8.05) compared to those without BC or depression. The relationship between BC and mortality was moderated by cardiovascular diseases, anemia, smoking, age, PIR, and marital status. Our analysis provides vital information on factors that could be helpful for interventions to reduce mortality risk among those with BC and depression. In addition, given the higher risk of mortality with co-occurring BC and depression, collaborative healthcare practices should help with widespread screening for and treatment of depression among BC survivors.

UNASSIGNED: Extreme hyperbilirubinemia is occasionally observed in intensive care unit (ICU) and non-ICU settings. This study examined the etiologies of extreme hyperbilirubinemia (bilirubin level ≥12 mg/dL) and the factors associated with the 30-day mortality.
UNASSIGNED: This retrospective observational cohort study identified 439 patients with extreme hyperbilirubinemia at the Gyeongsang National University Changwon Hospital between 2016 and 2020. The patients were classified into three groups and 11 diseases according to their etiology. The risk factors associated with 30-day mortality at the baseline were investigated using the Cox proportional hazards model.
UNASSIGNED: Of 439 patients with extreme hyperbilirubinemia, 287, 78, and 74 were in the liver cirrhosis/malignancy group, the ischemic injury group, and the benign hepatobiliary-pancreatic etiological group, respectively, with corresponding 30-day mortality rates of 42.9%, 76.9%, and 17.6%. The most common disease leading to hyperbilirubinemia was a pancreatobiliary malignancy (28.7%), followed by liver cirrhosis (17.3%), hepatocellular carcinoma (10.9%), and liver metastases (8.4%). The etiologies of hyperbilirubinemia, obstructive jaundice, infection, albumin level, creatinine level, and prothrombin time-international normalized ratio were independently associated with the 30-day mortality.
UNASSIGNED: This study suggests three etiologies of extreme hyperbilirubinemia in the ICU and non-ICU settings. The prognosis of patients with extreme hyperbilirubinemia depends largely on the etiology and the presence of obstructive jaundice.

OBJECTIVE: To explore the prevalence of synchronous and metachronous tonsillar cancer in patients with base of tongue cancer, as well as identifying potential risk factors linked to these secondary malignancies. We aim to answer the following question: Should bilateral tonsillectomy be recommended to patients diagnosed with base of tongue cancer?
METHODS: A case-series study was conducted at Aarhus University Hospital, including all patients with histologically confirmed base of tongue squamous cell carcinoma treated between January 2012 and December 2021. Data from electronic patient records, including diagnosis of prior, synchronous or metachronous tonsillar cancer, demographics, and clinical features were analysed. Fisher\'s exact test was performed to assess factors associated with synchronous and metachronous tonsillar cancer.
RESULTS: Among 198 patients with base of tongue cancer, 5.6% had a history of tonsillar cancer, either prior to (4.5%), synchronous (0.5%), or metachronous (0.5%) to the base of tongue diagnosis. The prevalence of synchronous or metachronous tonsillar cancer among patients without previous bilateral tonsillectomy was 1.2%. Patients with tonsillar cancer were older, had heavier smoking histories, and exhibited less frequent P16-overexpression.
CONCLUSIONS: Our findings deepen understanding of tonsillar cancer in patients with base of tongue cancer. The prevalence of synchronous or metachronous tonsillar cancer was found to be relatively low, suggesting that routine tonsillectomy for all base of tongue cancer patients is not warranted.