Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

BACKGROUND: The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. METHODS: Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. RESULTS: In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ± 15.8 years vs. 35.1 ± 13.7 years, P  = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ± 1.13 vs. 0.34 ± 0.81, P  = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P  = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P  = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P  = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P  = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P  = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P  = 0.002), musculoskeletal damage (P  = 0.023), cardiovascular impairment (P  = 0.009), and CYC use (P  = 0.001); while leukopenia (P  = 0.017), arthritis (P  = 0.014), and mycophenolate usage (P  = 0.013) rates were lower. CONCLUSIONS Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.
Humans ; Female ; Male ; Cross-Sectional Studies ; Sex Characteristics ; East Asian People ; Severity of Illness Index ; Lupus Erythematosus, Systemic/diagnosis* ; Lupus Nephritis/pathology* ; Registries ; Cyclophosphamide/therapeutic use* ; Thrombocytopenia ; Leukopenia/drug therapy* ; Arthritis

Actinin/genetics* ; Anemia ; Blood Platelets/pathology* ; Female ; Humans ; Male ; Megakaryocytes ; Mutation, Missense ; Pedigree ; Thrombocytopenia/genetics*

A 23-year-old Indian man presented with shortness of breath and new-onset confusion along with a rash on his chest on Postoperative Day 2, following internal fixation of his femur fracture. Although computed tomography pulmonary angiography was negative for filling defects in the pulmonary vasculature, it showed mosaic attenuation changes with some interlobular septal thickening. Magnetic resonance imaging of the brain showed patchy signal abnormalities, predominantly in the grey-white matter junction region with extensive susceptibility artefacts, consistent with petechial haemorrhages. The laboratory work-up showed thrombocytopenia and anaemia. A diagnosis of fat embolism syndrome was established, based on the clinical presentation combined with laboratory and imaging findings. The clinical and imaging features of fat embolism syndrome are discussed.
Brain ; pathology ; Dyspnea ; Embolism, Fat ; diagnostic imaging ; Femoral Fractures ; diagnostic imaging ; Humans ; Hypoxia ; India ; Magnetic Resonance Imaging ; Male ; Pulmonary Embolism ; Thrombocytopenia ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVE: To report on the incidence of nab-paclitaxel hypersensitivity reactions (HSRs) in patients with prior taxane HSR. METHODS: From 2005 to 2015, all patients who received nab-paclitaxel for a gynecologic malignancy were identified. Chart abstraction included pathology, prior therapy, indication for nab-paclitaxel, dosing, response, toxicities including any HSR, and reason for discontinuation of nab-paclitaxel therapy. RESULTS: We identified 37 patients with gynecologic malignancies with a history of paclitaxel HSR who received nab-paclitaxel. Six patients (16.2%) had a prior HSR to both paclitaxel and docetaxel while the other 31 patients had not received docetaxel. No patients experienced a HSR to nab-paclitaxel. Median number of cycles of nab-paclitaxel was 6 (range 2–20). Twelve patients received weekly dosing at 60 to 100 mg/m². The remainder of patients received 135 mg/m² (n=13), 175 mg/m² (n=9), or 225 mg/m² (n=3). Thirty four patients (91.9%) received nab-paclitaxel in combination with carboplatin (n=28, 75.7%), IP cisplatin (n=1, 2.7%), carboplatin and bevacizumab (n=3, 8.1%), or carboplatin and gemcitabine (n=2, 5.4%). Reasons for discontinuing nab-paclitaxel included completion of adjuvant therapy (n=16), progressive disease (n=18), toxicity (n=1), and death (n=1). There were no grade 4 complications identified during nab-paclitaxel administration. Grade 3 complications included: neutropenia (n=9), thrombocytopenia (n=4), anemia (n=1), and neurotoxicity (n=1). CONCLUSION: Nab-paclitaxel is well-tolerated with no HSRs observed in this series of patients with prior taxane HSR. Given the important role of taxane therapy in nearly all gynecologic malignancies, administration of nab-paclitaxel should be considered prior to abandoning taxane therapy.
Albumin-Bound Paclitaxel ; Anemia ; Bevacizumab ; Carboplatin ; Cisplatin ; Drug Hypersensitivity ; Drug Therapy ; Humans ; Hypersensitivity* ; Incidence ; Neutropenia ; Paclitaxel ; Pathology ; Thrombocytopenia

Plasma cell leukemia (PCL) is an aggressive form of multiple myeloma where there is hematogenous spread of abnormal plasma cells into the periphery. This is opposed to multiple myeloma, where the abnormal plasma cells stay in the bone marrow. PCL is more common in males than females, and is also more common in African-Americans than Caucasians. Signs and symptoms of PCL include, but are not limited to, renal insufficiency, hypercalcemia, anemia, lytic bone lesions, thrombocytopenia, hepatomegaly, and splenomegaly. Here, we discussed a case of a 71-year-old Caucasian female recently diagnosed with primary PCL with radiographic features of this disease throughout the body, with an emphasis on the maxillofacial skeleton and relevance from a dental standpoint.
Aged ; Anemia ; Bone Marrow ; Female ; Hepatomegaly ; Humans ; Hypercalcemia ; Leukemia, Plasma Cell* ; Male ; Maxilla* ; Multiple Myeloma ; Pathology ; Plasma Cells* ; Plasma* ; Renal Insufficiency ; Skeleton ; Splenomegaly ; Thrombocytopenia

Fever ; Humans ; Plasma Cells ; pathology ; Thrombocytopenia ; diagnosis ; pathology

BACKGROUND/AIMS: The mortality rate of pyogenic liver abscess (PLA) has decreased dramatically, but it remains a potentially life threatening disease. Most cases are cryptogenic or occur in elderly men with underlying biliary tract disease. Although several studies have addressed the characteristics and etiology of PLA, research on factors affecting PLA-associated mortality is lacking. This study intended to identify the clinical and radiological features, pathogens, complications, and predictors of mortality in Korean PLA patients. METHODS: The medical records of 231 PLA patients diagnosed at Yeungnam University Medical Center between January 2010 and January 2014 were analyzed. A diagnosis of PLA was made based on imaging studies and blood and abscess cultures. The clinical, radiological, and laboratory findings of patients were analyzed. RESULTS: The mean patient age was 64.0±12.9 years and the male to female ratio was 1.5:1. Klebsiella pneumoniae was the predominant organism isolated from hepatic abscesses (69.9%) and blood (74.2%). The most common complication was pleural effusion (35.8%) and most common co-infection was cholangitis (8.2%). The overall mortality rate of PLA was 6.9% (16/231), and was significantly higher in patients with a history of liver abscess (OR 5.970, 95% CI 1.207-29.529; p=0.028), bilirubinemia (>2 mg/dL) (OR 9.541, 95% CI 2.382-38.216; p=0.001), thrombocytopenia (<140×10(3)/µL) (OR 4.396, 95% CI 1.130-17.106; p=0.033), or anemia (<12 g/dL) (OR 13.277, 95% CI 1.476-119.423; p=0.021). CONCLUSIONS: The prognosis of PLA appears to be dependent on underlying pathologies and severity of condition. More aggressive treatment should be considered if a poor prognosis is expected.
Abscess ; Academic Medical Centers ; Aged ; Anemia ; Biliary Tract Diseases ; Cholangitis ; Coinfection ; Diagnosis ; Female ; Humans ; Hyperbilirubinemia ; Klebsiella pneumoniae ; Liver Abscess ; Liver Abscess, Pyogenic* ; Male ; Medical Records ; Mortality* ; Pathology ; Pleural Effusion ; Prognosis ; Retrospective Studies* ; Risk Factors ; Thrombocytopenia

The causes of cytopenia in patients with severe fever with thrombocytopenia syndrome (SFTS) are not fully understood until now. We reviewed the bone marrow (BM) findings of patients with SFTS to unravel the cause of the cytopenia. Three Korean SFTS were enrolled in this study. Thrombocytopenia, neutropenia, and anemia were detected in all three patients. Severe hypocellular marrow (overall cellularity <5%) and a decreased number of megakaryocytes were noted in one patient, and hypo-/normocellular marrow and an increased number of hemophagocytic histiocytes were observed in two patients. Megakaryocytes were relatively preserved in two patients. Although a limited number of cases are available, our observations suggest that both BM suppression and peripheral destruction or sequestration are causes of cytopenia of patients with SFTS. To the best of our knowledge, this is the first well documented pathologic evaluation of Korean SFTS.
Aged ; Aged, 80 and over ; Bone Marrow/*pathology ; Female ; Fever/*complications ; Histiocytes/*pathology ; Humans ; Male ; Middle Aged ; Neutropenia/complications ; Pancytopenia/complications ; Syndrome ; Thrombocytopenia/*complications/*immunology

The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.
Biomarkers/analysis ; Bone Marrow/*pathology ; Carcinoma, Hepatocellular/*diagnosis ; Humans ; Liver Neoplasms/*diagnosis ; Male ; Middle Aged ; Neoplasm Metastasis ; Positron Emission Tomography Computed Tomography ; Protein Precursors/analysis ; Prothrombin/analysis ; Thrombocytopenia/diagnosis ; Tomography, X-Ray Computed ; alpha-Fetoproteins/analysis