Costs associated with invasive Scedosporium and Lomentospora prolificans infections: a case-control study.

BACKGROUND: Little is known about the short- and long-term healthcare costs of invasive Scedosporium/Lomentospora prolificans infections, particularly in patient groups without haematological malignancy. This study investigated excess index hospitalization costs and cumulative costs of these infections. The predictors of excess cost and length of stay (LOS) of index hospitalization were determined. These estimates serve as valuable inputs for cost-effectiveness models of novel antifungal agents. METHODS: A retrospective case-control study was conducted at six Australian hospitals. Cases of proven/probable invasive Scedosporium/L. prolificans infections between 2011 and 2021 (n = 34) were matched with controls (n = 66) by predefined criteria. Cost data were retrieved from activity-based costing systems and analysis was performed from the Australian public hospital perspective. All costs were presented in 2022 Australian dollars (AUD). Median regression analysis was used to adjust excess costs of index hospitalization whereas cumulative costs up to 1.5 years follow-up were estimated using interval-partitioned survival probabilities. RESULTS: Invasive Scedosporium/L. prolificans infections were independently associated with an adjusted median excess cost of AUD36 422 (P = 0.003) and LOS of 16.27 days (P < 0.001) during index hospitalization. Inpatient stay was the major cost driver (42.7%), followed by pharmacy cost, of which antifungal agents comprised 23.8% of the total cost. Allogeneic haematopoietic stem cell transplant increased the excess cost (P = 0.013) and prolonged LOS (P < 0.001) whereas inpatient death within ≤28 days reduced both cost (P = 0.001) and LOS (P < 0.001). The median cumulative cost increased substantially to AUD203 292 over 1.5 years in cases with Scedosporium/L. prolificans infections. CONCLUSIONS: The economic burden associated with invasive Scedosporium/L. prolificans infections is substantial.

Gait biomechanics do not differ between adolescents with and without patellofemoral pain.

OBJECTIVES: To determine if adolescents with patellofemoral pain exhibit different biomechanical characteristics to asymptomatic adolescents during walking and running. METHODS: Twenty-eight adolescents with patellofemoral pain (16 male, 12 female, mean [SD] age: 14.3 [1.7] years) and 24 asymptomatic adolescents (13 male, 11 female, mean [SD] age: 14.1 [1.6] years) participated. Participants walked and ran on an instrumented treadmill in a standardized athletic shoe. Continuous hip, knee, and ankle joint angles and moments, and frontal plane pelvic motion were compared between groups using one-dimensional statistical parametric mapping independent t-tests (alpha <0.05). Cadence and stride length were compared between groups using independent t-tests. RESULTS: During walking, adolescents with patellofemoral pain had a higher hip extension moment at 7%-8% of the gait cycle (p = 0.04) and walked with a shorter stride length (mean difference [95% confidence interval] = -0.07 [-0.1, -0.01] m). There were no other differences between groups during walking. During running, adolescents with patellofemoral pain had greater knee flexion than asymptomatic adolescents at 35%-40% of the gait cycle (p = 0.04) and ran with a higher cadence (mean difference [95% confidence interval] = 5.8 [2.0, 9.5] steps/min). There were no other statistically significant differences between groups during running. CONCLUSIONS: Adolescents with patellofemoral pain demonstrate few biomechanical differences to asymptomatic adolescents during walking and running. The identified differences are likely of limited clinical importance. Biomechanical alterations which have been previously associated with patellofemoral pain in adults, may not need to be the target of management of adolescent patellofemoral pain.

Vulvar Ulcers: An Algorithm to Assist With Diagnosis and Treatment.

OBJECTIVES: Vulvar ulcers can be challenging to diagnose, manage, and treat. Ulcers can be nonspecific in appearance and have many etiologies. Description of the lesion is very important. METHODS: An interactive vulvar ulcer algorithm was created to aid in the evaluation, diagnosis, and treatment of vulvar ulcers. RESULTS: The algorithm flowchart begins with careful history and physical examination. Pending these, specific tests can be obtained to aid in diagnosis. The algorithm also links to appropriate treatments. The algorithm can be accessed on the International Society for the Study of Vulvovaginal Disease Web site ( issvd.org ). Each underlined word in the algorithm is a hyperlink that leads to a wealth of information on the topic that providers can use to direct testing and aid in diagnosis and treatment. CONCLUSIONS: The vulvar ulcer algorithm can help clinicians with diagnosis and treatment plans.

Outcomes After Lysis of Adhesions and Dilator Placement for Treatment of Vulvovaginal Agglutination Due to Lichen Planus.

OBJECTIVE: The aim of the study is to determine intraoperative and postoperative surgical outcomes for the treatment of vulvovaginal agglutination secondary to lichen planus (LP) following a standard protocol using intraoperative dilator placement and postoperative intravaginal steroid use. MATERIALS AND METHODS: This was a retrospective chart review of patients who underwent surgical management of vulvovaginal agglutination due to LP following a protocol that included surgical lysis of vulvovaginal adhesions, intraoperative dilator placement and removal 48 hours later, and high-potency intravaginal corticosteroid and regular dilator use thereafter. Demographic and clinical data were abstracted from the medical record and analyzed using descriptive statistics. RESULTS: Thirty-four patients, with mean age 51.2 ± 11 years and body mass index 32.8 ± 8.5 kg/m 2 , underwent lysis of vulvovaginal adhesions between 1999 and 2021 with 8 different surgeons at a single institution. The mean preoperative, immediate postoperative, and 6-week postoperative vaginal lengths were 2.8 ± 1.8 cm ( n = 18), 8.0 ± 1.9 cm ( n = 21), and 7.9 ± 2.2 cm ( n = 16), respectively. The mean estimated blood loss intraoperatively was 16 ± 15 mL. No patients had a documented surgical site infection or reoperation within 30 days after surgery. Of patients who had it documented ( n = 26), 70% (18/26) reported postoperative sexual activity. Where documented, 100% (18/18) reported preoperative dyspareunia, while 17% (3/18) did postoperatively. Six percent (2/34) had recurrent severe agglutination and 3% (1/34) underwent reoperation. CONCLUSIONS: Lysis of vulvovaginal adhesions, intraoperative dilator placement, and postoperative intravaginal corticosteroids with dilator use is a safe and effective treatment option to restore vaginal length for those with vulvovaginal LP.

Effect of concurrent strength and endurance training on run performance and biomechanics: A randomized controlled trial.

This parallel-group randomized controlled trial investigated the effect of concurrent strength and endurance (CSE) training on running performance, biomechanics, and muscle activity during overground running. Thirty moderately trained distance runners were randomly assigned to 10-week CSE training (n = 15; 33.1 ± 7.5 years) or a control group (n = 15; 34.2 ± 8.2 years). Participants ran ≥30 km per week and had no experience with strength training. The primary outcome measure was 2-km run time. Secondary outcome measures included lower limb sagittal plane biomechanics and muscle activity during running (3.89 m s-1 and maximal sprinting); maximal aerobic capacity (V̇O2 max); running economy; and body composition. CSE training improved 2-km run time (mean difference (MD): -11.3 s [95% CI -3.7, -19.0]; p = 0.006) and time to exhaustion during the V̇O2 max running test (MD 59.1 s [95% CI 8.58, 109.62]; p = 0.024). The CSE training group also reduced total body fat (MD: -1.05 kg [95% CI -0.21, -1.88]; p = 0.016) while total body mass and lean body mass were unchanged. Hip joint angular velocity during the early swing phase of running at 3.89 m s-1 was the only biomechanical or muscle activity variable that significantly changed following CSE training. CSE training is beneficial for running performance, but changes in running biomechanics and muscle activity may not be contributing factors to the performance improvement. Future research should consider other possible mechanisms and the effect of CSE training on biomechanics and muscle activity during prolonged running under fatigued conditions.

Fertility and Pregnancy Outcomes After Conservative Management of Adenocarcinoma In Situ of the Cervix.

OBJECTIVE: The aim of the study was to evaluate the pregnancy outcomes of women who underwent conservative management of adenocarcinoma in situ (AIS). MATERIALS AND METHODS: We conducted a retrospective chart review of patients diagnosed with AIS at a single tertiary institution between January 1, 1991, and December 31, 2019. We collected demographic data, AIS-specific information, and fertility outcomes and performed bivariate analyses to compare demographic characteristics and AIS-specific information between patients with and without hysterectomy after diagnosis. Patients with conservative management who achieved pregnancy were described. RESULTS: Among 87 patients with AIS, 38 (44%) underwent a hysterectomy within 6 months of diagnosis and 49 (56%) underwent conservative management. Six of 19 patients (32%) had residual AIS despite undergoing definitive management after an excisional procedure with negative margins and negative endocervical curettage (ECC). Nine of 19 patients (47%) had residual AIS after an excisional procedure with positive margins and/or a positive ECC. Patients who opted for conservative management were younger (median = 31.6 [interquartile range = 27.4-34.9] vs 38.5 y [32.3-44.8 y], p < .001) and nulligravid. Among patients with conservative management, there were 15 pregnancies and 14 live births (29%). Seven were preterm, although 2 were for medical indications. CONCLUSIONS: Residual AIS in patients with negative margins and ECC leading to definitive hysterectomy (32%) and the rate of preterm birth (36%) were higher than previous reports and nationally reported rates. However, only 1 patient had a preterm birth before 34 weeks. These findings reflect important information for counseling patients who elect for conservative management of AIS.

How do parents of school-aged children respond to their children's extending gestures?

Gesture plays an important role in early language development, as how parents respond to their children's gestures may help to facilitate language acquisition. Less is known about whether parental responses facilitate language learning later in childhood and whether responses vary depending on children's language ability. This study explored parental responses to extending gestures in a sample of school-aged children (aged six to eight years) with developmental language disorder, low-language and educational concerns, and typically developing children. Overall there were no group differences in the types of responses parents provided to extending gestures. Parents predominantly responded with positive feedback but also displayed moderate proportions of verbal translations and clarification requests. Within the DLD group, the proportion of parent translations was negatively associated with language ability. Our finding suggests that parent responses serve to enhance communication and engage children in tasks, but there is limited evidence that they support new language learning at this age.

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial†.

AIMS: Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1-7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. METHODS AND RESULTS: A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: -0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0-0.20; P = 0.048). Major adverse events were rare in both treatment groups. CONCLUSION: The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.

Randomized trial of combination cytokine and adult autologous bone marrow progenitor cell administration in patients with non-ischaemic dilated cardiomyopathy: the REGENERATE-DCM clinical trial.

AIMS: The REGENERATE-DCM trial is the first phase II randomized, placebo-controlled trial aiming to assess if granulocyte colony-stimulating factor (G-CSF) administration with or without adjunctive intracoronary (IC) delivery of autologous bone marrow-derived cells (BMCs) improves global left ventricular (LV) function in patients with dilated cardiomyopathy (DCM) and significant cardiac dysfunction. METHODS AND RESULTS: Sixty patients with DCM and left ventricular ejection fraction (LVEF) at referral of ≤45%, New York Heart Association (NYHA) classification ≥2 and no secondary cause for the cardiomyopathy were randomized equally into four groups: peripheral placebo (saline), peripheral G-CSF, peripheral G-CSF and IC serum, and peripheral G-CSF and IC BMC. All patients, except the peripheral placebo group, received 5 days of G-CSF. In the IC groups, this was followed by bone marrow harvest and IC infusion of cells or serum on Day 6. The primary endpoint was LVEF change from baseline to 3 months, determined by advanced cardiac imaging. At 3 months, peripheral G-CSF combined with IC BMC therapy was associated with a 5.37% point increase in LVEF (38.30% ± 12.97 from 32.93% ± 16.46 P = 0.0138), which was maintained to 1 year. This was associated with a decrease in NYHA classification, reduced NT-pro BNP, and improved exercise capacity and quality of life. No significant change in LVEF was seen in the remaining treatment groups. CONCLUSION: This is the first randomized, placebo-controlled trial with a novel combination of G-CSF and IC cell therapy that demonstrates an improvement in cardiac function, symptoms, and biochemical parameters in patients with DCM.

Ensuring implementation success: how should coach injury prevention education be improved if we want coaches to deliver safety programmes during training sessions?

Coaches play a major role in encouraging and ensuring that participants of their teams adopt appropriate safety practices. However, the extent to which the coaches undertake this role will depend upon their attitudes about injury prevention, their perceptions of what the other coaches usually do and their own beliefs about how much control they have in delivering such programmes. Fifty-one junior netball coaches were surveyed about incorporating the teaching of correct (safe) landing technique during their delivery of training sessions to junior players. Overall, >94% of coaches had strongly positive attitudes towards teaching correct landing technique and >80% had strongly positive perceptions of their own control over delivering such programmes. Coaches' ratings of social norms relating to what others think about teaching safe landing were more positive (>94%) than those relating to what others actually do (63-74%). In conclusion, the junior coaches were generally receptive towards delivering safe landing training programmes in the training sessions they led. Future coach education could include role modelling by prominent coaches so that more community-level coaches are aware that this is a behaviour that many coaches can, and do, engage in.

The acute effects of conventional, complex, and contrast protocols on lower-body power.

This study compared conventional, complex, and contrast protocols on peak power (PP) output. Static vs. dynamic contractions were also manipulated to determine the effect of these confounding variables. Eighteen recreationally trained men [age, 21.1 ± 3.3 years; body mass, 81.7 ± 15.9 kg; height, 182.8 ± 6.2 cm; 5 repetition maximum (5RM) half back squat, 119.2 ± 25.4 kg; 5RM/BW, 1.5 ± 0.2 kg] involved in sports including Australian Rules football, basketball, soccer, and rugby participated in this investigation. Five protocols were executed in a randomized order, a conventional protocol in which 3 sets of 4 countermovement jumps (CMJs) were performed 2 minutes apart. Contrast protocols using a heavy resistance conditioning action of either 4 repetitions with a 5RM load or a 5-second static back squat were alternated with sets of 4 CMJs. Complex conditions with 3 sets of 4 repetitions of a 5RM back squat or a 5-second static back squat were performed before the 3 sets of CMJs. In all conditions, 4 minutes of rest followed sets of heavy resistance exercises and 2 minutes of rest followed each set of CMJs. Individual set means and a total session mean were calculated from each CMJ performed during the session. Results showed that the conventional protocol produced significantly greater PP than all conditions except for the dynamic complex and the static contrast. Results suggest that the use of the complex and contrast protocols used in this investigation should not be used for acute increases in lower-body PP in recreationally trained individuals.

The Immediate Biomechanical Effects of a Flat, Flexible School Shoe in Adolescents with Patellofemoral Pain.

INTRODUCTION: Treatment options for adolescent patellofemoral pain (PFP) are limited. School footwear might be a suitable intervention to modulate patellofemoral joint (PFJ) loads in adolescents with PFP. This study examined the immediate effects of a flat, flexible school shoe compared with a traditional school shoe on knee joint kinematics and kinetics, and PFJ reaction force during walking and running in adolescents with PFP. METHODS: A total of 28 adolescents (12 female, 16 male; mean ± SD age, 14.3 ± 1.7 yr) with PFP walked and ran on an instrumented treadmill in two randomly ordered conditions: (i) flat, flexible school shoe and (ii) traditional school shoe. Three-dimensional marker trajectory and ground reaction force data were sampled at 250 and 1000 Hz, respectively. Continuous ankle and knee joint angles and moments, PFJ reaction force, and ankle power were compared between conditions using one-dimensional statistical parametric mapping paired t -tests ( α < 0.05). RESULTS: Walking in the flat, flexible school shoe resulted in a significant reduction in knee flexion (15%-35% of gait cycle, P < 0.001), knee extension moment (15%-40% of gait cycle, P < 0.001), and PFJ reaction force (15%-40% of gait cycle, P < 0.001) compared with the traditional school shoe. During running, knee flexion (10%-33% of gait cycle, P < 0.001), knee extension moment (15%-25% of gait cycle, P < 0.001), and PFJ reaction force (15%-25% of gait cycle, P < 0.001) were lower when wearing the flat, flexible school shoe compared with the traditional school shoe. CONCLUSIONS: PFJ reaction force is reduced when adolescents walk and run in a flat, flexible school shoe compared with a traditional school shoe. Flat, flexible school shoes may be an effective intervention to modulate biomechanical factors related to PFP.

Activity profiles of the Australian female netball team players during international competition: implications for training practice.

In elite sport, to remain competitive at the international level, it is critical to understand the game demands on players to ensure sport specific training programmes are designed for optimal athlete preparation and conditioning. In netball, recent research examining the activity patterns of players at the elite level is lacking, with only one study undertaken on this level of competition in the past 30 years. Therefore, the aim of this study was to provide coaches with up to date knowledge of player activity patterns as a basis for the design of optimal sport specific training programmes. The Australian female netball team were analysed using video footage of three international test matches. Player activity was categorised into five movement and eight game-based activities; and further classified as work or rest. Results suggest that differences in the current game exist when compared to the previous analysis. Positional differences were also found with regard to player activity confirming the need for an individualised component of training based on player position.

Video analysis of anterior cruciate ligament injury situations in the women's Australian football league.

BACKGROUND: Anterior cruciate ligament (ACL) injury rates in the Women's Australian Football League (AFLW) are alarmingly high. Understanding injuries within their sporting context is important to develop effective injury prevention strategies, yet there is currently little knowledge of how ACL injuries occur to AFLW players. This study addressed the common scenarios and characteristics of AFLW ACL injuries. METHODS: Online match and AFLW club injury reports identified 38 ACL injury cases. After excluding injuries where footage was unavailable (i.e. training, pre-season games), a video analysis of 21 match ACL injuries from the 2017-2020 AFLW seasons was performed. We examined match characteristics, and the player's movements and body postures preceding and at the estimated time of injury. Descriptive frequencies and relative proportions were determined across the assessed categories. RESULTS: Non-contact ACL injuries were frequently observed (n = 13, 61.9%), while contact preceding the injury event (i.e. indirect contact) was also common (n = 10, 47.6%). The most common game situation was direct defence (i.e. defending an opponent in possession) (n = 14, 66.7%). Sidestep cutting was the most prevalent movement (n = 11, 52.4%), with this commonly performed while applying defensive pressure (n = 6 of 11, 54.6%). CONCLUSION: Sidestep cutting when applying defensive pressure is the most common non-contact ACL injury scenario in the AFLW. Preceding contact potentially contributing to a player's loss of balance was another prominent AFLW scenario. AFLW players may benefit from injury prevention programs emphasising appropriate sidestep cutting technique during reactive defensive scenarios, and maintenance of lower limb postures known to withstand knee loading relative to the sporting task.

Australian secondary school principals', parents', and students' attitudes to prescribed school footwear guidelines.

BACKGROUND: Adolescents are often required to wear footwear that adheres to uniform guidelines at secondary school. There is a paucity of literature on factors influencing school footwear choice and what drives the development of school footwear guidelines. The aims of this study were to describe (i) current school footwear guidelines in secondary schools across Australia, (ii) factors that influence footwear choice in secondary school students and their parents, and (iii) principals, parents, and students' beliefs on factors which contribute to school footwear guidelines. METHODS: An online survey was distributed to principals, secondary school students (aged 14-19 years) and their parents across Australia. The survey included questions on current school footwear guidelines, factors influencing footwear choice (for students and parents), participants beliefs on the effect footwear has on musculoskeletal health, current and previous lower limb pain, and beliefs on factors that contribute to school footwear guidelines. Parent and student responses to factors that influence their footwear choice were compared using proportional odds logistic regression. Students and parents' responses to factors influencing footwear guidelines were compared to principal responses using proportional odds logistic regression. Significance was set at an alpha of < 0.05. RESULTS: Eighty principals, 153 parents and 120 secondary school students responded to the survey. 96% (77/80) of principals reported that their schools have set guidelines for school footwear. 88% of principals considered comfort to be important when developing school footwear guidelines. Proportional odds logistics regression showed that parents and students were 3.4 and 4.9 times more likely, respectively, than principals to rate comfort as being important when schools develop footwear guidelines. More than 40% of students reported experiencing musculoskeletal pain, and 70% of these students reported the pain to be exacerbated when in their school shoes. Less than a third of participants considered healthcare recommendations important to the development of footwear guidelines. CONCLUSIONS: Nearly all principals that participated in this survey had set guidelines for school footwear. There is a discord between parents, students, and principals on the importance that factors such as comfort, play in the development of school footwear guidelines.

Flat flexible school shoes for adolescents with patellofemoral pain: a randomised, assessor-blinded, parallel-group feasibility trial.

Objectives: To determine the feasibility of conducting a large-scale randomised controlled trial on the efficacy of flat, flexible school footwear versus traditional school footwear in adolescents (aged 12-18 years) with patellofemoral pain (PFP). Methods: Adolescents with PFP were recruited for this study. Participants were randomised to wear either a (1) flat, flexible school shoe or (2) a traditional school shoe. Participants wore the shoes as per school requirements for 12 weeks. Feasibility was assessed by (1) adherence to allocated shoe wear of ≥75% of total weekly school shoe wear time (recorded through weekly log sheets), (2) a recruitment rate of one participant per fortnight and (3) a dropout rate of ≤ 20%. Descriptive statistics were used for feasibility outcomes. Results: 24 adolescents (15 men, 9 women, mean (SD) age 14.3 (1.7) years) participated in this study. Two participants (8%) were lost to follow-up. The recruitment rate was 1.7 participants per fortnight. 11 of 12 participants (91%) in the flat flexible shoe group and 9 of 10 participants (90%) in the traditional shoe group met the minimum adherence for shoe wear. Mean weekly shoe wear was 20 (7.6) and 21 (4.5) hours per week in the flat, flexible, and traditional shoe groups, respectively. Conclusion: Our results indicate that progression to a full-scale randomised controlled trial is feasible based on the current protocol. A full-scale randomised controlled trial powered to detect estimates of treatment efficacy using flat, flexible school shoes versus traditional school shoes is warranted and will guide evidence-based management of adolescent PFP.

High Rates of Seroprotection and Seroconversion to Vaccine-Preventable Infections in the Early Post-Autologous Stem Cell Transplant Period.

In patients early post-autologous stem cell transplant, seroprotection rates were high for Hemophilus influenzae type B and tetanus toxoid (70%-90%) but lower for Streptococcus pneumoniae (30%-50%) including after revaccination. There were high rates of seropositivity (67%-86%) to measles, mumps, and rubella and varicella zoster virus. Durability of protection requires assessment.

Prospective comprehensive profiling of immune responses to COVID-19 vaccination in patients on zanubrutinib therapy.

Zanubrutinib-treated and treatment-naïve patients with chronic lymphocytic leukaemia (CLL) or Waldenstrom's macroglobulinaemia were recruited in this prospective study to comprehensively profile humoral and cellular immune responses to COVID-19 vaccination. Overall, 45 patients (median 72 years old) were recruited; the majority were male (71%), had CLL (76%) and were on zanubrutinib (78%). Seroconversion rates were 65% and 77% following two and three doses, respectively. CD4+ and CD8+ T-cell response rates increased with third dose. In zanubrutinib-treated patients, 86% developed either a humoral or cellular response. Patients on zanubrutinib developed substantial immune responses following two COVID-19 vaccine doses, which further improved following a third dose.

Evolution of Humoral and Cellular Immunity Post-Breakthrough Coronavirus Disease 2019 in Vaccinated Patients With Hematologic Malignancy Receiving Tixagevimab-Cilgavimab.

Background: In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods: We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results: In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell-depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions: Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post-breakthrough COVID-19 in vaccinated patients with HM.