The coronavirus disease 2019 (COVID-19) vaccines are authorized for use in numerous countries worldwide. Several cutaneous findings are reported after severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) vaccination. Here, we report the case of a patient with a rapid onset of alopecia areata immediately after receiving the second dose of the COVID-19 vaccine. Alopecia areata is a common autoimmune disease leading to non-scarring hair loss. Among the many cutaneous adverse effects reported after the anti-SARS-COV2 vaccination, no episodes of alopecia areata have been described to date. In this paper, we report the first case of alopecia areata after COVID-19 vaccination described in the literature with a revision of cases of alopecia areata reported after other types of vaccination. Although the significance of these skin reactions is not yet known, further studies will certainly clarify whether the development of alopecia areata or other forms of immune-mediated reactions could represent a positive prognostic factor regarding immune protection from SARS-CoV-2.

OBJECTIVETo investigate the prognostic value of thymidylate synthase (TS), topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment (5-Fu).

METHODSThe biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome.

RESULTSThe expressions of those biomarkers were not correlated with clinical therapeutic response, but with time to progression (TTP) and/or overall survival (OS). Patients with low expression of TS had significantly longer TTP (P < 0.05) and in OS (P < 0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P < 0.05). As compared with any biomarker, the combination of any two biomarkers still possessed no predictive value to therapeutic response, but an enhanced predictive value to prognosis. The median time to progression in patients with low expression of TS, or Ki-67, or both were 9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo-1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients with low expression of two biomarkers as compared with those with high expression (P = 0.031).

CONCLUSIONTS, Topo-1, and Ki-67 are not predictive for chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting prognosis. The combination of any two biomarkers can provide more powerful prognostic information for advanced colorectal cancer patients.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; enzymology ; DNA Topoisomerases, Type I ; metabolism ; Female ; Fluorouracil ; administration & dosage ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Middle Aged ; Prognosis ; Thymidylate Synthase ; metabolism ; Treatment Outcome

PURPOSE: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. MATERIALS AND METHODS: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibswere subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-stepwhole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients' peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. RESULTS: Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none ofwhich, except one, sharedwith the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. CONCLUSION: In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.
Carcinoma, Squamous Cell* ; Disease Susceptibility ; DNA ; Epithelial Cells* ; Exome ; Female* ; High-Throughput Nucleotide Sequencing ; Humans ; Lung Neoplasms ; Lung* ; Multifactorial Inheritance ; Precision Medicine* ; Smoking

Background/Aims: Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. Methods: MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. Results: Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. Conclusion It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.

Background/Aims: Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. Methods: MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. Results: Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. Conclusion It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.

Purpose: To assess the relationship between clinical and semen characteristics and assisted reproductive technology (ART) outcomes with different birth weight (BW) categories in a cohort of infertile men. Materials and Methods: Data from 1,063 infertile men were analyzed. Patients with BW ≤2,500, 2,500–4,000, and ≥4,000 g were considered as having low BW (LBW), normal BW (NBW), and high BW (HBW), respectively. Testicular volume (TV) was assessed with a Prader orchidometer. Serum hormones were measured in all cases. Semen analyses were categorized based on 2021 World Health Organization reference criteria. Sperm DNA fragmentation (SDF) was tested in every patient and considered pathological for SDF >30%. ART outcomes were available for 282 (26.5%) patients. Descriptive statistics and logistic regression analyses detailed the association between semen parameters and clinical characteristics and the defined BW categories. Results: Of all, LBW, NBW, and HBW categories were found in 79 (7.5%), 807 (76.0%), and 177 (16.5%) men, respectively. LBW men had smaller TV, presented higher follicle-stimulating hormone (FSH) but lower total testosterone levels compared to other groups (all p<0.01). Sperm progressive motility (p=0.01) and normal morphology (p<0.01) were lower and SDF values were higher (all p<0.01) in LBW compared to other groups. ART pregnancy outcomes were lower in LBW compared to both NBW and HBW categories (26.1% vs. 34.5% vs. 34.5%, p=0.01). At multivariable logistic regression analysis, LBW was associated with SDF >30% (odd ratio [OR] 3.7; p<0.001), after accounting for age, Charlson Comorbidity Index (CCI), FSH, and TV. Similarly, LBW (OR 2.2; p<0.001), SDF >30% (OR 2.9; p<0.001) and partner’s age (OR 1.3; p=0.001) were associated with negative ART outcomes, after accounting for the same predictors. Conclusions LBW was associated with impaired clinical and semen characteristics in infertile men compared to both NBW and HBW. SDF and ART outcomes were significantly worse in the LBW group.

Purpose: Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera (PV). Despite its overall good safety profile, its use also in relatively young patients raises an interest on its potential impact on spermatogenesis. To perform a systematic review of all published articles investigating fertility in male patients affected by SCD, ET, and PV and treated with HU. Two paradigmatic case reports of patients affected by PV and ET, respectively, have been also reported. Materials and Methods: PubMed, EMBASE, and Cochrane databases were queried for all the published studies indexed up to November 15th, 2022. A combination of the following keywords was used: “hydroxyurea,” “fertility,” “male,” “sperm,” “sickle cell anaemia,” “sickle cell disease,” “essential thrombocythemia,” “polycythaemia vera.” Results: Of 48 articles identified, 8 studies, involving 161 patients, were eligible for inclusion. Overall, the number of spermatogonia per round cross section of seminiferous tubule were decreased in patients with SCD compared to healthy males. HU treatment was always associated with a worsening of semen parameters, even up to azoospermia. Notably, treatment discontinuation was associated with an improvement of semen parameters and a trend toward normalization in the case of PV and ET, with a less clear amelioration in men with SCD. In both our patients with either PV or ET, HU discontinuation was associated with a significant improvement of spermatogenesis with successful spontaneous pregnancies. Conclusions Published evidence do not consistently report normalization of spermatogenesis after HU discontinuation in SCD cases. Conversely, the literature almost consistently reported an improvement of semen parameters at the discontinuation of HU therapy in PV and ET cases. Our real-life two cases confirmed those findings. The willing of fatherhood and the need for effective fertility treatment warrant further research to improve work-up management in men with hematological disorders.

BACKGROUND/AIMS: The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC. METHODS: A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators. RESULTS: A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245). CONCLUSIONS: PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.
Adenocarcinoma/*diagnosis/surgery ; Aged ; CA-19-9 Antigen/blood ; Feasibility Studies ; Female ; Humans ; Male ; *Models, Biological ; Neoplasm Recurrence, Local/*diagnosis ; Pancreatic Neoplasms/*diagnosis/surgery ; Prognosis ; Retrospective Studies ; Tumor Markers, Biological/*blood

BACKGROUND AND PURPOSE: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm³ [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm³ [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm³ [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSIONS: These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.
Animals ; Brain Injuries ; Brain Ischemia ; Brain ; Cohort Studies ; Cortical Spreading Depression ; Humans ; Linear Models ; Magnetic Resonance Imaging ; Migraine Disorders ; Migraine with Aura ; Models, Animal ; Perfusion ; Risk Factors ; Stroke

Objective To analyze the safety and effectiveness of robot-assisted laparoscopic partial nephrectomy(RLPN) for cT2 renal tumors in international multi-centers.Methods This study was conducted to collect information on surgical procedures performed by RLPN and robot assisted laparoscopic radical nephrectomy (RRN) in nineteen international urological centers from January 2012 to December 2017.RLPN were performed in 159 patients (118 males and 41 females),with the average age of (59.3 ± 13.2) years,body mass index(BMI) of (28.7 ± 5.4)kg/m2,preoperative GFR of (77.3 ± 22.1) ml/min.RRN were performed in 219 patients,with the average age of (62.0 ± 12.9) years,BMI of (28.7 ±6.1) kg/m2,preoperative GFR of (71.4 ± 20.3) ml/min.There was no statistical difference between the two groups in gender and BMI.The age of the patients in RLPN group was younger than that in RRN group,and the preoperative GFR was better.The patient's baseline demographics,perioperative data,tumor pathology,oncologic outcomes,and renal function (GFR) were recorded.Results All 378 cases underwent successful surgery.The operation time of RLPN was 150 min(65-353 min),which was shorter than that of RRN [180 min(85-361 min),P ＜ 0.001].The intra-operative blood loss of RLPN was more than that of RRN [150 ml (40-3 000 ml) vs.100 ml (10-1 100 ml),P ＜ 0.001].The incidence of intra-operative complications were not statistically different between the two groups [5.7％ (9/159) vs.3.2％ (7/219),P =0.240].The incidence of postoperative complications was higher in the RLPN group than that in RRN group [19.5％ (31/159) vs.10.5％ (23/219),P =0.014],but there was no significant difference in the incidence of complications of grade 3 or above [4.4％ (7/159) vs.2.3％ (5/219),P =0.246].The recurrence-free survival rate of RLPN group was higher than that of RRN group [91.4％ (117/128) vs.81.9％ (167/204),P =0.013],and RLPN group was more conducive to renal function protection (P ＜ 0.001).Conclusions RLPN for cT2 tumors can obtain effective tumor control rate and better renal function preservation.It could be an acceptable alternative for surgical management of cT2 tumors.